tbuckley/cabot-search huggingface dataset:
Improved outcomes in ex-smokers with COPD: a UK primary care observational cohort study
Authors: Lynn Josephs, David Culliford, Matthew Johnson, Mike Thomas
Journal: European Respiratory Journal (2017)

Smoking cessation in chronic obstructive pulmonary disease (COPD) reduces accelerated forced expiratory volume in 1 s decline, but impact on key health outcomes is less clear. We studied the relationship of smoking status to mortality and hospitalisation in a UK primary care COPD population. Using patient-anonymised routine data in the Hampshire Health Record Analytical Database, we identified a prevalent COPD cohort, categorising patients by smoking status (current, ex- or never-smokers). Three outcomes were measured over 3 years (2011–2013): all-cause mortality, respiratory-cause unplanned hospital admission and respiratory-cause emergency department attendance. Survival analysis using multivariable Cox regression after multiple imputation was used to estimate hazard ratios for each outcome by smoking status, adjusting for measured confounders (including age, lung function, socioeconomic deprivation, inhaled medication and comorbidities). We identified 16 479 patients with COPD, mean± sd age 70.1±11.1 years. Smoking status was known in 91.3%: 35.1% active smokers, 54.3% ex-smokers, 1.9% never-smokers. Active smokers predominated among younger patients. Compared with active smokers (n=5787), ex-smokers (n=8941) had significantly reduced risk of death, hazard ratio (95% confidence interval) 0.78 (0.70–0.87), hospitalisation, 0.82 (0.74–0.89) and emergency department attendance, 0.78 (0.70–0.88). After adjusting for confounders, ex-smokers had significantly better outcomes, emphasising the importance of effective smoking cessation support, regardless of age or lung function.
Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy
Authors: Norikazu Masuda, Soo-Jung Lee, Shoichiro Ohtani, Young-Hyuck Im, Eun-Sook Lee, Isao Yokota, Katsumasa Kuroi, Seock-Ah Im, Byeong-Woo Park, Sung-Bae Kim, Yasuhiro Yanagita, Shinji Ohno, Shintaro Takao, Kenjiro Aogi, Hiroji Iwata, Joon Jeong, Aeree Kim, Kyong-Hwa Park, Hironobu Sasano, Yasuo Ohashi, Masakazu Toi
Journal: New England Journal of Medicine (2017)

Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear.We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival.The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval [CI], 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group.After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843 .).
Former Guyanese health minister sentenced in US for illegal prescribing
Authors: Owen Dyer
Journal: BMJ (2017)

A Long Island doctor has been sentenced to 50 months’ imprisonment for illegal prescribing of oxycodone. Noel Blackman, 69, is a former health minister of Guyana and a former executive member of the World Health Organization.

Until his arrest, Blackman was also dean of academic affairs at the Georgetown American University medical school in Guyana.

He was arrested a year ago, on a Guyana bound plane waiting to take off from New York’s John F Kennedy Airport. Police found $30 000 (£23 100, €26 800) in cash hidden in his luggage. Wascar Castillo, Blackman’s office manager, was charged last year and sentenced to 36 months …
Abstract 325: COX2 Expression is Increased in Human and Mouse Calcific Aortic Valve Disease and COX2 Inhibition Blocks the Induction of Osteogenic Gene Expression in Valve Interstitial Cells
Authors: Elaine E Wirrig, Robert B Hinton, Katherine E Yutzey
Journal: Circulation Research (2013)

Calcific aortic valve disease (CAVD) is considered a disease of aging and is characterized by calcific nodule formation, stenosis of the valve, and induction of osteogenic gene expression. The klotho deficient mouse model of premature aging exhibits CAVD evident in calcific lesions in the aortic valve annulus. Klotho deficient mice develop calcification by 6 weeks of age, with minimal immune cell infiltration and increased osteogenic gene expression. Microarray analyses performed on aortic valve tissues of wild type and klotho deficient mice demonstrate that cyclooxygenase 2 (COX2) expression is increased in klotho deficient mice. We hypothesize that increased COX2 expression contributes to aortic valve calcification and that COX2 inhibition prevents osteogenic gene expression in aortic valve interstitial cells (aVICs). In klotho deficient mice, COX2 protein expression is increased throughout regions of valve calcification relative to wild type controls. Prior to the formation of calcified valve lesions, increased COX2 expression is localized to areas at risk of developing calcification in klotho deficient mice. Thus increased COX2 expression precedes valve calcification. In human explanted calcific aortic valves, COX2 expression also is increased in mineralized regions compared to controls. In bone, COX2 deficiency inhibits osteogenic gene induction. The ability of COX2 inhibition to block osteogenic gene expression was examined using porcine aVICs. Treatment of aVICs with osteogenic media induces bone markers, including osteocalcin, in addition to increasing COX2 gene expression. Furthermore, inhibition of COX2 activity in cells cultured under osteogenic conditions results in significantly decreased expression of osteogenic genes compared to controls. In vivo studies in progress provide initial evidence that loss of COX2 activity reduces aortic valve calcification in klotho deficient mice. In conclusion, COX2 expression is increased in regions of aortic valve calcification in both human and mouse CAVD tissues, and COX2 inhibition suppresses osteogenic gene expression in cultured aVICs. Targeting COX2 enzyme activity may be a potential therapeutic option for preventing or reducing aortic valve calcification in the future.
Charles Henry James Swan
Authors: Jonathan R B Green
Journal: BMJ (2017)

Charles Henry James Swan was born in Wolverhampton and educated at Wolverhampton Grammar School. During training in the West Midlands, he obtained an MD from Birmingham University and then spent a year at the New York Medical College, USA, having received a Wellcome travel grant.

He was appointed consultant physician and gastroenterologist at the then North Staffordshire Hospital …
Degree of nephrotoxicity after intermediate or high-dose cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC).
Authors: Chantal Driessen, Maike Uijen, Winette T.A. Van Der Graaf, J. H. Kaanders, Tom Nijenhuis, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2014)

6056 Background: CRT with cisplatin 100 mg/m2 on days 1, 22, 43 (cis100) is standard treatment for LAHNC and nasopharyngeal cancers (NPC) patients (pts). An alternative CRT schedule consists of cisplatin 40 mg/m2 weekly during six weeks (cis40). A direct prospective comparison of these 2 schedules has not been performed, yet. Data on the influence of these schedules on cisplatin-based nephrotoxicity are scarce. This study compared the occurrence of cisplatin-induced nephrotoxicity between these 2 CRT schedules. Methods: All pts treated with CRT for LAHNC or NPC from 2003 until 2011 in the Radboud university medical center were studied retrospectively. One hundred forty-four LAHNC/NPC pts were included, of whom 40 received cis100 and 104 received cis40. Serum creatinine at baseline and maximal rise during treatment were collected. An increase of 25% was established as clinically relevant. Nephrotoxicity was scored according to both the CTCAE version 3.0 and version 4.03. Results: Baseline serum creatinine was equal in both groups. During treatment with cis40, 17.3% developed an increase of ≥25% serum creatinine versus 77.5% treated with cis100 (p<0.05). According to the CTCAE version 4.03, nephrotoxicity grade 1 occurred in 40% and 68%, grade 2 in 53% and 7%, grade 3 in 5% and 0%, and grade 4 in 2% and 0% (p<0.05) in cis100 and cis40 LAHNC/NPC pts, respectively. Scoring according to CTCAE v 3.0 showed grade 1 in 42% and 5%, grade 2 in 8% and 0%, grade 3 in 2% and 0% in cis100 and cis40 pts, respectively. In the cis100 group 3/40 pts developed chronic renal dysfunction, versus 0/104 in the cis40 group. Pts treated with cis100 were admitted to the hospital more often en needed more often extra hydration (p<0.05). Conclusions: Significantly less nephrotoxicity occurs in pts treated with cis40 CRT compared to cis100 CRT. We suggest that LAHNC/NPC pts with renal impairment are treated with cis40 CRT. The CTCAE v 4.03 is more appropriate in scoring nephrotoxicity than the CTCAE v 3.0. Until recently the CTCAE v 3.0 was used, which has lead to an underscoring of nephrotoxicity in studies using cisplatin-containing CRT schedules.
GPs oppose MPs' proposals on removing patients from lists Clinical governance needs time and money GPs given guidance over millennium planning BMA Council Elections
Authors: E M Armstrong
Journal: BMJ (1999)

# GPs oppose MPs' proposals on removing patients from lists {#article-title-2}

The General Practitioners Committee opposes the suggestion of the select committee on public administration that GPs' powers to remove patients from their lists should be qualified by changing their terms of service.

In their response to the health service ombudsman's annual report the MPs said that GPs should give reasons to the health authority for removing a patient from their lists and that the authority would have to approve the removal (15 May, p 1309). At present there is no contractual obligation to give reasons, but the GPC agrees that it is good practice and common courtesy to give a reason. In its 1996 guidance on removing patients the committee says that “when trust has irretrievably broken down it is in the patient's interest to find a new GP.”

The GPC believes that the select committee's recommendation that patients should have a right of appeal if they thought that they had been wrongly removed would be counterproductive.

The ombudsman's report also deals with complaints in primary care, and the GPC emphasised that when GPs faced complaints they should be considered innocent until proved guilty. The medical defence organisations …
Efficacy of rebamipide-gargle for chemotherapy-induced oral mucositis.
Authors: Masato Nakamura, Akiyoshi Shinohara, Toshihide Onikubo, Kumi Nakamura, Harumi Kamikawa, Kyota Oda, Katsunori Tauchi
Journal: Journal of Clinical Oncology (2013)

9637 Background: Chemotherapy-induced oral mucositis (CIOM) is a severe adverse event resulting from cancer chemotherapy, and causes severe pain which impacts eating, nutrition, infection and overall quality of life. CIOM can result in unplanned treatment interruptions including dose reduction or treatment delay. Toxic free radicals and several pro-inflammatory cytokines produced by anti-cancer drugs have been reported to correlate with CIOM. Rebamipid, an endogenous inducer of prostaglandins, is widely used for gastric ulcers and gastritis in Asia. It has been shown to increase gastric endogenous prostaglandin E2 and I2, to promote gastric epithelial mucin, to behave as an oxygen–free radical scavenger, and to have other anti-inflammatory actions. In this study, we made a rebamipide gargle using rebamipide and ultrahydrogel, which is added for mucosal protection and to sustain the rebamipide on oral mucosa for a long time. Methods: The objective of this study is to evaluate the efficacy of the rebamipide gargle in relieving CIOM. Each 300ml of rebamipide gargle is made by combining rebamipide 600mg, high molecular weight polyethylene oxide 3g, carrageenin 1.2g, pineapple flavor and water. Patients were instructed to use the rebamipide gargle 5-6 times a day. The severity of CIOM was assessed according to the National Cancer Institute Common TerminologyCriteria for Adverse Events (CTCAE version 4.0). Results: From November 2009 to December 2012, 175 patients with CIOM were enrolled in this study (colorectal cancer 95 patients, breast cancer 32, gastric cancer 22, lung cancer 14, and other cancers 12). The patients’ CTCAE grades (3/2/1/0) changed from (n=13/64/98/0) to (0/10/103/62) respectively after initiation of rebamipide gargle (p&lt;.01; paired t test). A decrease in CTCAE was observed in 142 patients (81.1%) including 62 patients (35.4%) achieving grade 0. The mean duration to best response was 14 days (range: 1-49), and rebamipide gargle was continued 42 days (range: 5-970).There were no unexpected safety events. Conclusions: Rebamipide gargle was well tolerated and demonstrated significant therapeutic response for CIOM.
Venetoclax Synergizes with Radiotherapy for Treatment of B-cell Lymphomas
Authors: Shyril O'Steen, Damian J. Green, Ajay K. Gopal, Johnnie J. Orozco, Aimee L. Kenoyer, Yukang Lin, D. Scott Wilbur, Donald K. Hamlin, Darrell R. Fisher, Mark D. Hylarides, Theodore A. Gooley, Amelia Waltman, Brian G. Till, Oliver W. Press
Journal: Cancer Research (2017)

Abstract Constitutive B-cell receptor signaling leads to overexpression of the antiapoptotic BCL-2 protein and is implicated in the pathogenesis of many types of B-cell non-Hodgkin lymphoma (B-NHL). The BCL-2 small-molecule inhibitor venetoclax shows promising clinical response rates in several lymphomas, but is not curative as monotherapy. Radiotherapy is a rational candidate for combining with BCL-2 inhibition, as DNA damage caused by radiotherapy increases the activity of pro-apoptotic BCL-2 pathway proteins, and lymphomas are exquisitely sensitive to radiation. We tested B-NHL responses to venetoclax combined with either external beam radiotherapy or radioimmunotherapy (RIT), which joins the selectivity of antibody targeting with the effectiveness of irradiation. We first tested cytotoxicity of cesium-137 irradiation plus venetoclax in 14 B-NHL cell lines representing five lymphoma subtypes. Combination treatment synergistically increased cell death in 10 of 14 lines. Lack of synergy was predicted by resistance to single-agent venetoclax and high BCL-XL expression. We then assessed the efficacy of external beam radiotherapy plus venetoclax in murine xenograft models of mantle cell (MCL), germinal-center diffuse large B-cell (GCB-DLBCL), and activated B-cell (ABC-DLBCL) lymphomas. In each model, external beam radiotherapy plus venetoclax synergistically increased mouse survival time, curing up to 10%. We finally combined venetoclax treatment of MCL and ABC-DLBCL xenografts with a pretargeted RIT (PRIT) system directed against the CD20 antigen. Optimal dosing of PRIT plus venetoclax cured 100% of mice with no detectable toxicity. Venetoclax combined with radiotherapy may be a promising treatment for a wide range of lymphomas Cancer Res; 77(14); 3885–93. ©2017 AACR.
The feasibility of romberg quotient in assessment of balance after sport concussion
Authors: Matti Vartiainen, Anu Holm, Sanna Koskinen, Laura Hokkanen
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate the feasibility of a computerised balance test and a calculated Romberg Quotient in acute recognition of concussion Design Prospective pilot study. Setting Finnish national ice hockey league. Participants Four teams participated in the study (n=113, male). Nine athletes who sustained a head/neck-related injury and control group of seven non-concussed volunteer players were followed. Study procedure All participants underwent the baseline assessment before season. The study period was one hockey season 2009- 2010. All game related concussions during this time were recorded. Post-concussion assessment was administered within 36 hours after injury. Outcome measures Balance was measured using a portable computerised platform. Romberg test stances were used on hard surface and soft foam. The participants stood still for 30 seconds with a closed stance. A relative balance change, Romberg Quotient (RQ), was assessed by calculating the ratio between eyes open, and eyes closed parameters. RQ was computed for sway length, area and velocity in each condition Main results Concussed and control group did not differ in balance measures at baseline. At post-injury, soft foam measures showed a difference between groups in sway length (U=5.0, p=0.005) and velocity (U=5.0, p=0.005). Among the concussed, RQ mean in sway velocity was 2.02 (1.7–2.3, 95% confidence limits) at baseline and 2.14 (1.9–2.4) post-injury Conclusions Alternating between different visual and/or somatosensory conditions in balance testing brings out the effect of concussions. RQ is easy to calculate regardless of the measurement systems or scales and can be used as valid tool in sport concussion measurement Competing interests None.
Evaluation of Stem Cell Mobilization in Patients with Multiple Myeloma after Lenalidomide-Based Induction Chemotherapy within the GMMG-HD6 Trial
Authors: Patrick Wuchter, Uta Bertsch, Hans-Juergen Salwender, Markus Munder, Mathias Haenel, Axel Benner, Natalia Becker, Roland Fenk, Jan Duerig, Igor Wolfgang Blau, Katharina Lisenko, Jens Hillengass, Marc S. Raab, Marc Andrea Baertsch, Andrea Seidel-Glaetzer, Anthony D Ho, Ullrich Graeven, Christof Scheid, Katja Weisel, Hartmut Goldschmidt
Journal: Blood (2016)
Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children
Authors: Agnes Trautmann, Sven Schnaidt, Beata S. Lipska-Ziętkiewicz, Monica Bodria, Fatih Ozaltin, Francesco Emma, Ali Anarat, Anette Melk, Marta Azocar, Jun Oh, Bassam Saeed, Alaleh Gheisari, Salim Caliskan, Jutta Gellermann, Lina Maria Serna Higuita, Augustina Jankauskiene, Dorota Drozdz, Sevgi Mir, Ayse Balat, Maria Szczepanska, Dusan Paripovic, Alexandra Zurowska, Radovan Bogdanovic, Alev Yilmaz, Bruno Ranchin, Esra Baskin, Ozlem Erdogan, Giuseppe Remuzzi, Agnieszka Firszt-Adamczyk, Elzbieta Kuzma-Mroczkowska, Mieczyslaw Litwin, Luisa Murer, Marcin Tkaczyk, Helena Jardim, Anna Wasilewska, Nikoleta Printza, Kibriya Fidan, Eva Simkova, Halina Borzecka, Hagen Staude, Katharina Hees, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2017)

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.
Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis
Authors: Kazuyoshi Ishigaki, Yuta Kochi, Akari Suzuki, Yumi Tsuchida, Haruka Tsuchiya, Shuji Sumitomo, Kensuke Yamaguchi, Yasuo Nagafuchi, Shinichiro Nakachi, Rika Kato, Keiichi Sakurai, Hirofumi Shoda, Katsunori Ikari, Atsuo Taniguchi, Hisashi Yamanaka, Fuyuki Miya, Tatsuhiko Tsunoda, Yukinori Okada, Yukihide Momozawa, Yoichiro Kamatani, Ryo Yamada, Michiaki Kubo, Keishi Fujio, Kazuhiko Yamamoto
Journal: Nature Genetics (2017)
Severe Onycholysis and Eyelash Trichomegaly Following Use of New Selective Pan-FGFR Inhibitors
Authors: Sarah Bétrian, Carlos Gomez-Roca, Emmanuelle Vigarios, Jean Pierre Delord, Vincent Sibaud
Journal: JAMA Dermatology (2017)

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