bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Quality Improvement Initiative to Improve Medication Management in an Acute Care for Elders Program Through Integration of a Clinical Pharmacist
Authors: Chowdhury Tasmiah P. , Starr Rebecca , Brennan Maura , Knee Alexander , Ehresman Mike , Velayutham Lalitha , Malanowski Alexander J. , Courtney Heidi-Ann , Stefan Mihaela S. 
Published: July 2018

Purpose: To describe the implementation and impact of integrating a clinical pharmacist into interdisciplinary Acute Care for Elderly (ACE) rounds at a teaching hospital. Methods: Pre- and postanalyses were performed 6 months before and 12 months after the intervention. We report the total number, type, and frequency of recommendations made by the clinical pharmacist, the acceptance rate by the physician, and interventions on potentially inappropriate medications (PIM). Results: Among the 588 patients who met the ACE inclusion criteria, mean age was 81.2 years, 54.9% were female, and 79.8% were of white race. A total of 1243 pharmacy recommendations were recorded. The median number of recommendations per patient increased from a median of 1 (range: 1-7) in the preintervention to 2 (1-13) in the postintervention period, resulting in an incidence rate ratio of 1.25 (95% confidence interval [CI]: 1.10-1.40). The main categories of recommendations were dose adjustment, avoidance of inappropriate therapy, and prevention of adverse drug events. In the postintervention period, there was an increase in recommendations among analgesics (from 3.7% to 7.5%), PIMs (from 12% to 14%), and, in particular, antidepressant/antipsychotics (from 1.9% to 6.0%). The acceptance rate of the recommendations remained roughly the same (86.5% vs 84.4%). Conclusion: Proactive involvement of a clinical pharmacist in ACE rounds resulted in a substantial increase in recommendation for medication changes, most notably for PIMs. These recommendations generally were accepted by physicians. The integration of a clinical pharmacist requires significant dedicated time but leads to increased recognition of drug-related problems in the acute-care setting, resulting in improved patient outcomes.
Subchondral drilling for chondral flaps reduces the risk of total hip arthroplasty in femoroacetabular impingement surgery at minimum five years follow-up
Authors: Haefeli Pascal C , Tannast Moritz , Beck Martin , Siebenrock Klaus A , Büchler Lorenz 
Published: July 2018

Introduction: The best treatment of acetabular chondral flaps during surgery for femoroacetabular impingement (FAI) is unknown. We asked if subchondral drilling improves clinical and radiographic outcome and if there are factors predicting failure. Methods: We treated 79 patients with symptomatic FAI and acetabular chondral flaps with surgical hip dislocation between January 2000 and December 2007. Exclusion of all patients with previous hip pathology or trauma resulted in 62 patients (80 hips). The chondral flap was slightly debrided in 43 patients/51 hips (control group). In 28 patients/29 hips (study group), additional osseous drilling was performed. 4 patients (5 hips, 6%) were lost to follow-up. Mean follow-up was 9 years (5–13 years). The groups did not differ in demographic data, radiographic parameters or follow-up. Clinical outcome was assessed with the Merle d’Aubigné score, modified Harris Hip Score and University of California Los Angeles activity score and progression of osteoarthritis with the Tönnis grade. Results: No patient underwent conversion to total hip arthroplasty (THA) in the drilling group compared to 7 patients (8 hips, 16%) in the control group ( p = 0.005); in the remaining hips, clinical scores and progression of Tönnis grade did not differ. Increased acetabular coverage, age and body mass index were univariate predictive factors for conversion to THA. No drilling was as an independent predictive factor for conversion to THA (hazard ratio 58.07, p = 0.009). Conclusion: Subchondral drilling under acetabular chondral flaps during surgical treatment of FAI is an effective procedure to reduce the rate of conversion to THA.
Survival Outcomes of Retreatment with Trastuzumab and Cytotoxic Chemotherapy for HER2-Positive Recurrent Patients With Breast Cancer Who Had Been Treated with Neo/adjuvant Trastuzumab Plus Multidrug Chemotherapy: A Japanese Multicenter Observational Study
Authors: Yamashiro Hiroyasu , Sawaki Masataka , Masuda Norikazu , Okumura Yasuhiro , Takano Toshimi , Tokunaga Eriko , Saito Tsuyoshi , Sagara Yasuaki , Yamazaki Kosuke , Kawaguchi Yoshihiro , Lee Tecchuu , Ozaki Shinji , Yamagami Kazuhiko , Yamamoto Naohito , Kuroi Katsumasa , Suwa Hirofumi , Ohtani Shoichiro , Ito Toshikazu , Yasuno Shinji , Morita Satoshi , Ohno Shinji , Toi Masakazu 
Published: July 2018

Background: There are little data on the usefulness of trastuzumab (TZM) retreatment as the first-line treatment for patients with HER2 (human epidermal growth factor receptor 2)–positive breast cancer recurrence after perioperative treatment with TZM. Aim: To clarify the outcome and safety of TZM retreatment in patients with recurrent HER2-positive breast cancer. Method: An observational study was conducted on patients who relapsed after primary systemic therapy with TZM using the central registration system. The primary end point was progression-free survival (PFS). Secondary end points consisted of the response rate, overall survival (OS), and safety. Result: In total, 34 patients were registered between July 2009 and June 2012. The median follow-up time was 23.7 months (2-24 months). The 1- and 2-year PFS rates were 46.9% (95% confidence interval (95% CI): 29.2%-62.9%) and 29.8% (95% CI: 15.0%-46.3%), respectively (median 10.6 months). The median PFS time for patients receiving TZM combined with CTx was 13.9 months. The 1-and 2-year OR rates were 93.9 (95% CI: 77.9%-98.4%) and 84.8% (95% CI: 67.4%-93.4%). Trastuzumab-induced grade 3/4 adverse events were not observed. Conclusions: This study suggests that the PFS and OS in Japanese patients who relapsed after perioperative TZM therapy improved or were similar to those in previous reports. Differences in patient backgrounds and treatments must be considered when interpreting the results. Trastuzumab should be used combination with CTx and/or HTx for retreatment. Retreatment with TZM is safe. Trial registration: UMIN000002738.
Successful Endoscopic Treatment of Post-esophagectomy Refractory Reflux Using OverStitch: The First Clinical Case
Authors: Nagase Hirotsugu , Yamasaki Makoto , Yanagimoto Yoshitomo , Kanemura Takashi , Higashi Shigeyoshi , Momose Kota , Kato Ryo , Miyazaki Yasuhiro , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Miyata Hiroshi , Takiguchi Shuji , Mori Masaki , Doki Yuichiro , Nakajima Kiyokazu 
Published: July 2018

Aims: The reflux of duodeno-gastric contents into the remnant esophagus (gastric tube-esophageal reflux: GTER) is a significant issues in long-term esophageal cancer survivors after radical esophagectomy. We attempted endoscopic valve (funnel) creation for prevention for GTER using OverStitch endoscopic suturing system. Methods: The OverStitch was mounted onto a standard double-channel endoscope. Under general anesthesia, the funnel creation was attempted by placing semi-full thickness sutures on the gastric wall, at 3 cm distal to the primary esophago-gastric anastomosis. The postoperative outcomes were also evaluated. Results: In total, 4 sutures were needed and the operating time was 62 minutes without complication. The endoscopic and swallowing studies, as well as pH profile, were all improved postoperatively. The patient’s quality of life was dramatically improved with complete disappearance of night-time reflux in spine position. Conclusions: Endoscopic antireflux funnel creation was feasible and safe. This procedure may become a useful treatment for patients with severe GTER after esophagectomy.
Pus Samples in Complicated Appendicitis: An Important Investigation or a Waste of Resources: A Prospective Cohort Study
Authors: Akingboye A. A. , Davies B. , Tien T. 
Published: July 2018

Background and Aims: Appendicitis is a common presentation to hospital with appendectomy being the treatment of choice. Pre-operative administration of broad-spectrum antibiotics is common, but obtaining intra-abdominal pus samples is not. After an initial 6-month retrospective audit and departmental teaching on the importance of intra-peritoneal pus sampling, we aimed to determine whether intra-operative pus samples changed antibiotic management. Materials and Methods: Following the initial audit cycle, a 6-month prospective cohort study was conducted. Clinical data were collected on a predetermined proforma to assess the effectiveness of the intervention and antibiotic prescribing practice. The data collected during the whole 1-year period was analyzed. Results: During the 1-year period, 440 patients were identified as undergoing a laparoscopic procedure. After exclusion, 261 patients were identified as undergoing laparoscopic appendectomies, of which 141 (54%) were classified as complicated laparoscopic appendectomies. A total of 35 out of 141 (25%) pus samples were sent of which 24 (17%) resulted in positive cultures, with only nine of these positive cultures reported prior to the patient being discharged. No patient had their antibiotic regimen changed as a result of the culture results. There were three cases of cultures resistant to local antibiotics, but without significant clinical outcome. One of these patients developed a post-operative complication, but the antibiotic regimen was changed to broad spectrum rather than a specific antibiotic based on culture sensitivity. Of the 141 patients with complicated laparoscopic appendectomies, five (3.5%) developed post-operative complications: one readmission requiring a laparoscopic washout for pelvic collection, three (2%) cases of pelvic collections managed conservatively, and one case of prolonged paralytic ileus managed non-operatively. Conclusion: Overall, none of the patients with positive cultures had a change in prescribed antibiotics based on culture results. Hence, the routine practice of intra-peritoneal pus sampling following complicated appendicitis remains of little clinical value.
Five-Year Outcome of Laparoscopic Sleeve Gastrectomy, Resolution of Comorbidities, and Risk for Cumulative Nutritional Deficiencies
Authors: Kikkas E. M. , Sillakivi T. , Suumann J. , Kirsimägi Ü. , Tikk T. , Värk P. R. 
Published: July 2018

Background and Aims: The aim of this study was to evaluate the long-term (5-year follow-up) results of laparoscopic sleeve gastrectomy in terms of weight loss and obesity-related comorbidities, as well as the risk factors associated with postoperative nutritional deficiencies. Material and Methods: The first 99 consecutive patients who underwent laparoscopic sleeve gastrectomy for the treatment of morbid obesity between October 2008 and August 2011 at Tartu University Hospital were followed prospectively in cohort study. The outpatient hospital follow-up visits were conducted at 3 months, 1 year, and 5 years postoperatively. At 5 years, the follow-up rate was 90.9%; 86 laparoscopic sleeve gastrectomy patients were included in final analysis. Results: The mean excess weight loss (%EWL) was 44.3% ± 13.0%, 75.8% ± 23.1%, and 61.0% ± 24.3% at 3 months, 1 year, and 5 years, respectively. A linear association between preoperative weight and weight at 5 years was found. Remission rates at 5-year follow-up for type 2 diabetes, hypertension, dyslipidemia, and obstructive sleep apnea were 68.8%, 32.7%, 27.4%, and 61.5%, respectively (all p < 0.05). There was a statistical difference (p < 0.05) in the dynamics of triglyceride, low-density lipoprotein, and high-density lipoprotein level at 5-year follow-up but the level of total cholesterol did not show significant improvement. The risk for cumulative iron, vitamin B12 deficiency, and anemia was 20%, 48%, and 28%, respectively. Conclusion: In conclusion, laparoscopic sleeve gastrectomy ensured long-term excess weight loss 61.0% at 5 years. Laparoscopic sleeve gastrectomy has a long-term effect on significant improvement in the median values of triglycerides, low-density lipoproteins, and high-density lipoproteins, but not on total cholesterol levels. There is a risk of postoperative vitamin B12 and iron deficiency.
Calcium-RasGRP2-Rap1 signaling mediates CD38-induced migration of chronic lymphocytic leukemia cells
Authors: Mele Silvia , Devereux Stephen , Pepper Andrea G. , Infante Elvira , Ridley Anne J. 
Published: July 2018

Key Points
Basal intracellular Ca2+ levels and migration increase with higher CD38 expression in CLL cells. Rap1 and the Rap1 guanine-nucleotide exchange factor RasGRP2 are required for CLL migration and regulated by CD38 levels.
Burden and risk factors forPseudomonas aeruginosacommunity-acquired pneumonia: a multinational point prevalence study of hospitalised patients
Authors: Restrepo Marcos I. , Babu Bettina L. , Reyes Luis F. , Chalmers James D. , Soni Nilam J. , Sibila Oriol , Faverio Paola , Cilloniz Catia , Rodriguez-Cintron William , Aliberti Stefano 
Published: July 2018

Pseudomonas aeruginosais a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated withP. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated withP. aeruginosa-CAP.We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification ofP. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistantP. aeruginosa-CAP.The prevalence ofP. aeruginosaand antibiotic-resistantP. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate ofP. aeruginosaCAP in patients with prior infection/colonisation due toP. aeruginosaand at least one of the three independently associated chronic lung diseases (i.e.tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate ofP. aeruginosa-CAP was 2% in patients without priorP. aeruginosainfection/colonisation and none of the selected chronic lung diseases.The multinational prevalence ofP. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients.
REM-associated sleep apnoea: prevalence and clinical significance in the HypnoLaus cohort
Authors: Acosta-Castro Patricia , Hirotsu Camila , Marti-Soler Helena , Marques-Vidal Pedro , Tobback Nadia , Andries Daniela , Waeber Gérard , Preisig Martin , Vollenweider Peter , Haba-Rubio José , Heinzer Raphael 
Published: July 2018

This study determined the prevalence of rapid eye movement (REM) related sleep-disordered breathing (REM-SDB) in the general population and investigated the associations of REM-SDB with hypertension, metabolic syndrome, diabetes and depression.Home polysomnography (PSG) recordings (n=2074) from the population-based HypnoLaus Sleep Cohort (48.3% men, 57±11 years old) were analysed. The apnoea–hypopnoea index was measured during REM and non-REM sleep (as REM-AHI and NREM-AHI, respectively). Regression models were used to explore the associations between REM-SDB and hypertension, diabetes, metabolic syndrome and depression in the entire cohort and in subgroups with NREM-AHI <10 events·h−1and total AHI <10 events·h−1.The prevalence of REM-AHI ≥20 events·h−1was 40.8% in the entire cohort. An association between increasing REM-AHI and metabolic syndrome was found in the entire cohort and in both the NREM-AHI and AHI subgroups (p-trend=0.014, <0.0001 and 0.015, respectively). An association was also found between REM-AHI ≥20 events·h−1and diabetes in both the NREM-AHI <10 events·h−1(odds ratio (OR) 3.12 (95% CI 1.35–7.20)) and AHI <10 events·h−1(OR 2.92 (95% CI 1.12–7.63)) subgroups. Systolic and diastolic blood pressure were positively associated with REM-AHI ≥20 events·h−1.REM-SDB is highly prevalent in our middle-to-older age sample and is independently associated with metabolic syndrome and diabetes. These findings suggest that an increase in REM-AHI could be clinically relevant.
Interactions between life expectancy and the incidence and mortality rates of cancer in China: a population‐based cluster analysis
Authors: Gu Xiuying , Zheng Rongshou , Xia Changfa , Zeng Hongmei , Zhang Siwei , Zou Xiaonong , Yang Zhixun , Li He , Chen Wanqing 
Published: July 2018

AbstractBackgroundThe relationship between cancer and life expectancy is well established in both developed and developing countries. China is a vast country with significant geographical differences in population structure and healthcare, and thus provides a unique opportunity to analyze the complex relationship between life expectancy and cancer incidence and mortality rates.MethodsCancer data were extracted for a total of 255 units (cities or counties) from the 2013 National Central Cancer Registry. Life expectancy data at the unit level were obtained from the National Centers for Disease Control and Prevention. Linear regression analysis was used to analyze the relationship between life expectancy and crude incidence and mortality rates of cancer. In a separate analysis, life expectancy was rated as low (< 76.0 years), middle (76–80 years), or high (> 80 years).ResultsOverall, the cancer incidence and mortality rates positively correlated with life expectancy in both sexes (R at 0.37 and 0.50, P < 0.001). The correlation was significant for the following cancers: lung, colorectal, prostate, bladder and pancreas, as well as for lymphoma in men (R 0.36–0.58, P < 0.001), lung, breast, colorectal, thyroid, uterus, and ovary in women (R 0.18–0.51, P < 0.001). We failed to observe an association between upper gastrointestinal cancer and life expectancy. The number of cities/counties with low, middle and high life expectancy levels were 110, 101 and 44, respectively. The highest age‐standardized cancer incidence rate was observed in areas with a high life expectancy level (192.83/100,000). The highest age‐standardized mortality rate was in areas with the lowest life expectancy (118.44/100,000). Cancers of the stomach, liver and esophagus are major cancer types in areas with low and middle life expectancy. In contrast, areas with high life expectancy had high incidence and mortality rates of colorectal cancer, breast cancer in women and prostate cancer in men.ConclusionsLonger life expectancy is associated with higher overall cancer incidence and mortality in China. The cancer pattern also varies substantially across areas with different life expectancy levels. Life expectancy levels must be considered when developing strategies to prevent and treat cancers.
Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient–Level Analysis of Multiple Randomized Trials (SEAL)
Authors: Shi Qian , Schmitz Norbert , Ou Fang-Shu , Dixon Jesse G. , Cunningham David , Pfreundschuh Michael , Seymour John F. , Jaeger Ulrich , Habermann Thomas M. , Haioun Corinne , Tilly Hervé , Ghesquieres Hervé , Merli Francesco , Ziepert Marita , Herbrecht Raoul , Flament Jocelyne , Fu Tommy , Coiffier Bertrand , Flowers Christopher R. 
Published: July 2018

Purpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R2WLS) and Copula bivariable ( R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R2WLS = 0.83; R2Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R2WLS = 0.77; R2Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.
A PIM-CHK1 signaling pathway regulates PLK1 phosphorylation and function during mitosis
Authors: Adam Kévin , Cartel Maëlle , Lambert Mireille , David Laure , Yuan Lingli , Besson Arnaud , Mayeux Patrick , Manenti Stéphane , Didier Christine 
Published: July 2018

ABSTRACT
Although the kinase CHK1 is a key player in the DNA damage response (DDR), several studies have recently provided evidence of DDR-independent roles of CHK1, in particular following phosphorylation of its S280 residue. Here, we demonstrate that CHK1 S280 phosphorylation is cell cycle-dependent and peaks during mitosis. We found that this phosphorylation was catalyzed by the kinase PIM2, whose protein expression was also increased during mitosis. Importantly, we identified polo-like kinase 1 (PLK1) as a direct target of CHK1 during mitosis. Genetic or pharmacological inhibition of CHK1 reduced the activating phosphorylation of PLK1 on T210, and recombinant CHK1 was able to phosphorylate T210 of PLK1 in vitro. Accordingly, S280-phosphorylated CHK1 and PLK1 exhibited similar specific mitotic localizations, and PLK1 was co-immunoprecipitated with S280-phosphorylated CHK1 from mitotic cell extracts. Moreover, CHK1-mediated phosphorylation of PLK1 was dependent on S280 phosphorylation by PIM2. Inhibition of PIM proteins reduced cell proliferation and mitotic entry, which was rescued by expressing a T210D phosphomimetic mutant of PLK1. Altogether, these data identify a new PIM–CHK1–PLK1 phosphorylation cascade that regulates different mitotic steps independently of the CHK1 DDR function.
This article has an associated First Person interview with the first author of the paper.