bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan–Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors
Authors: Tabernero Josep , Bahleda Rastislav , Dienstmann Rodrigo , Infante Jeffrey R. , Mita Alain , Italiano Antoine , Calvo Emiliano , Moreno Victor , Adamo Barbara , Gazzah Anas , Zhong Bob , Platero Suso J. , Smit Johan W. , Stuyckens Kim , Chatterjee-Kishore Moitreyee , Rodon Jordi , Peddareddigari Vijay , Luo Feng R. , Soria Jean-Charles 
Published: September 2015

Purpose JNJ-42756493 is an orally administered pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor. This first-in-human study evaluates the safety, pharmacokinetics, and pharmacodynamics and defines the recommended phase II dose (RP2D) of JNJ-42756493. Patients and Methods Eligible patients with advanced solid tumors received escalating doses of JNJ-42756493 from 0.5 to 12 mg administered continuously daily or JNJ-42756493 10 or 12 mg administered intermittently (7 days on/7 days off). Results Sixty-five patients were enrolled. The most common treatment-emergent adverse events included hyperphosphatemia (65%), asthenia (55%), dry mouth (45%), nail toxicity (35%), constipation (34%), decreased appetite (32%), and dysgeusia (31%). Twenty-seven patients (42%) experienced grade ≥ 3 treatment-emergent adverse events, and one dose-limiting toxicity of grade 3 ALT elevation was observed at 12 mg daily. Maximum-tolerated dose was not defined. Nine milligrams daily was considered as the initial RP2D; however, tolerability was improved with intermittent schedules, and 10 mg administered on a 7-days-on/7-days-off schedule was considered the final RP2D. Pharmacokinetics were linear, dose proportional, and predictable, with a half-life of 50 to 60 hours. Dose-dependent elevations in serum phosphate, a manifestation of pharmacodynamic effect, occurred in all patients starting at 4 mg daily. Among 23 response-evaluable patients with tumor FGFR pathway alterations, four confirmed responses and one unconfirmed partial response were observed in patients with glioblastoma and urothelial and endometrial cancer (all with FGFR2 or FGFR3 translocations); 16 patients had stable disease. Conclusion JNJ-42756493 administered at 10 mg on a 7-days-on/7-days-off schedule achieved exposures at which clinical responses were observed, demonstrated pharmacodynamic biomarker activity, and had a manageable safety profile.
Racial/Ethnic Differences in Inpatient Palliative Care Consultation for Patients With Advanced Cancer
Authors: Sharma Rashmi K. , Cameron Kenzie A. , Chmiel Joan S. , Von Roenn Jamie H. , Szmuilowicz Eytan , Prigerson Holly G. , Penedo Frank J. 
Published: September 2015

PurposeInpatient palliative care consultation (IPCC) may help address barriers that limit the use of hospice and the receipt of symptom-focused care for racial/ethnic minorities, yet little is known about disparities in the rates of IPCC. We evaluated the association between race/ethnicity and rates of IPCC for patients with advanced cancer.Patients and MethodsPatients with metastatic cancer who were hospitalized between January 1, 2009, and December 31, 2010, at an urban academic medical center participated in the study. Patient-level multivariable logistic regression was used to evaluate the association between race/ethnicity and IPCC.ResultsA total of 6,288 patients (69% non-Hispanic white, 19% African American, and 6% Hispanic) were eligible. Of these patients, 16% of whites, 22% of African Americans, and 20% of Hispanics had an IPCC (overall P < .001). Compared with whites, African Americans had a greater likelihood of receiving an IPCC (odds ratio, 1.21; 95% CI, 1.01 to 1.44), even after adjusting for insurance, hospitalizations, marital status, and illness severity. Among patients who received an IPCC, African Americans had a higher median number of days from IPCC to death compared with whites (25 v 17 days; P = .006), and were more likely than Hispanics (59% v 41%; P = .006), but not whites, to be referred to hospice.ConclusionInpatient settings may neutralize some racial/ethnic differences in access to hospice and palliative care services; however, irrespective of race/ethnicity, rates of IPCC remain low and occur close to death. Additional research is needed to identify interventions to improve access to palliative care in the hospital for all patients with advanced cancer.
Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non–Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial
Authors: Kelly Karen , Altorki Nasser K. , Eberhardt Wilfried E.E. , O'Brien Mary E.R. , Spigel David R. , Crinò Lucio , Tsai Chun-Ming , Kim Joo-Hang , Cho Eun Kyung , Hoffman Philip C. , Orlov Sergey V. , Serwatowski Piotr , Wang Jiuzhou , Foley Margaret A. , Horan Julie D. , Shepherd Frances A. 
Published: September 2015

Purpose Epidermal growth factor receptor (EGFR) –tyrosine kinase inhibitors have proven efficacy in advanced non–small-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRm-positive subgroup.
Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer
Authors: Tosoian Jeffrey J. , Mamawala Mufaddal , Epstein Jonathan I. , Landis Patricia , Wolf Sacha , Trock Bruce J. , Carter H. Ballentine 
Published: September 2015

Purpose To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active-surveillance program. Methods Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model. Results A total of 1,298 men (median age, 66 years) with a median follow-up of 5 years (range, 0.01 to 18.00 years) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range, 0.01 to 18 years). Factors associated with grade reclassification were older age (hazard ratio [HR], 1.03 for each additional year; 95% CI, 1.01 to 1.06), prostate-specific antigen density (HR, 1.21 per 0.1 unit increase; 95% CI, 1.12 to 1.46), and greater number of positive biopsy cores (HR, 1.47 for each additional positive core; 95% CI, 1.26 to 1.69). Factors associated with intervention were prostate-specific antigen density (HR, 1.38 per 0.1 unit increase; 95% CI, 1.22 to 1.56) and a greater number of positive biopsy cores (HR, 1.35 for one additional positive core; 95% CI, 1.19 to 1.53). Conclusion Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention.
The association between self-image and defence mechanisms in a group of adolescent patients receiving psychiatric treatment
Authors: Treger Bartosz , Matusiak Feliks , Pilecki Maciej , Rogoż Monika 
Published: September 2015

CelCelem badania była eksploracja zależności pomiędzy różnymi aspektami obrazu siebie, a mechanizmami obronnymi u osób w okresie adolescencji. W badaniu uwzględniono podział na grupy ze względu na podjęcie lub nie leczenia psychiatrycznego.MetodaDane pochodzą od dwóch grup: klinicznej (30 osób), którą stanowili pacjenci młodzieżowi oddziału stacjonarnego Kliniki Psychiatrii Dzieci i Młodzieży Szpitala Uniwersyteckiego w Krakowie oraz kontrolnej (40 osób), która stanowiła młodzież ucząca się w liceum ogólnokształcącym. W badaniu użyto Kwestionariusza Obrazu Siebie autorstwa Offera oraz Kwestionariusza do oceny mechanizmów obronnych DSQ-40.WynikiBadane grupy nie różniły się od siebie poziomem dojrzałości mechanizmów obronnych, pacjenci mieli statystycznie istotnie niższy obraz siebie niż młodzież z grupy kontrolnej. W obu grupach stosowaniu dojrzałych mechanizmów obronnych towarzyszył korzystny obraz siebie, natomiast używanie mniej dojrzałych mechanizmów obronnych związane było z niekorzystnym obrazem siebie. Porównanie grup ujawniło odmienne powiązania pomiędzy poszczególnymi aspektami obrazu siebie a stosowanymi mechanizmami obronnymi, w tym zwłaszcza mechanizmem projekcji. Ilość istotnych zależności była większa w grupie klinicznej.WnioskiW kontekscie zaniżonego obrazu siebie badanie ujawniło znacznie takich mechanizmów obronnych jak projekcja, acting out, somatyzacji czy fantazji schizoidalnych. Jednocześnie uzyskane wyniki wydają się potwierdzać hipotezę, że ocena dojrzałości mechanizmów obronnych w okresie adolescencji jest mniej jednoznaczna i tym samym mniej użyteczna klinicznie
The Impact of Workaround Difficulty on Frontline Employees’ Response to Operational Failures: A Laboratory Experiment on Medication Administration
Authors: Tucker Anita L. 
Published: September 2015

Operational failures persist, in part because employees work around them without engaging in actions to prevent recurrence. To break this cycle, we investigate the impact of work design factors on responses to operational failures. We use hospital nurses as subjects in a laboratory experiment, where, unknown to them, two medication administration supplies are missing. We observe their real-time responses to the two failures and whether they contribute an improvement idea. We randomly assign half of the participants to an experiment location far away from a satellite pharmacy where the missing supplies can be obtained (“difficult condition”), and the other half are located near the satellite pharmacy (“easy condition”). Both conditions contain risky, against-policy supplies that can be used to complete the work tasks, giving participants a choice between policy-compliant workarounds and risky, against-policy workarounds. In the first study, we find that participants in the difficult condition are more likely to contribute improvement ideas but are less likely to use policy-compliant workarounds. A second experiment with a 2 × 2 design shows that participants in the difficult condition who have high access to the process owner are more likely to use policy-compliant workarounds than when they have low access. Our results suggest that hospitals can increase communication about operational failures by deliberately making it difficult to work around them while simultaneously providing a high level of access to process owners. Otherwise, nurses encountering operational failures are likely to resort to against-policy workarounds, a behavior observed in practice. This paper was accepted by Serguei Netessine, operations management.
Metal-on-polyethylene versus metal-on-metal bearing surfaces in total hip arthroplasty
Authors: Briggs T. W. R. , Hanna S. A. , Kayani B. , Tai S. , Pollock R. C. , Cannon S. R. , Blunn G. W. , Carrington R. W. J. 
Published: September 2015

The long term biological effects of wear products following total hip arthroplasty (THA) are unclear. However, the indications for THA are expanding, with increasingly younger patients undergoing the procedure. This prospective, randomised study compared two groups of patients undergoing THA after being randomised to receive one of two different bearing surfaces: metal-on-polyethylene (MoP) n = 22 and metal-on-metal (MoM) n = 23. We investigated the relationship between three variables: bearing surface (MoP vs MoM), whole blood levels of chromium (Cr) and cobalt (Co) and chromosomal aberrations in peripheral lymphocyte pre-operatively and at one, two and five years post-surgery. Our results demonstrated significantly higher mean cobalt and chromium (Co and Cr) blood levels in the MoM group at all follow-up points following surgery (p < 0.01), but there were no significant differences in the chromosomal aberration indices between MoM and MoP at two or five years (two years: p = 0.56, p = 0.08, p = 0.91, p = 0.51 and five years: p = 0.086, p = 0.73, p = 0.06, p = 0.34) for translocations, breaks, loss and gain of chromosomes respectively. Regression analysis showed a strong linear relationship between Cr levels and the total chromosomal aberration indices in the MoM group (R2 = 0.90016), but this was not as strong for Co (R2 = 0.68991). In the MoP group, the analysis revealed a poor relationship between Cr levels and the total chromosomal aberration indices (R2 = 0.23908) but a slightly stronger relationship for Co (R2 = 0.64292). Across both groups, Spearman’s correlation detected no overall association between Co and Cr levels and each of the studied chromosomal aberrations. There remains no clear indication which THA bearing couple is the most biocompatible, especially in young active patients. While THA continues to be very successful at alleviating pain and restoring function, the long-term biological implications of the procedure still require further scrutiny. Cite this article: Bone Joint J 2015;97-B:1183–91.
Intra-articular and portal infiltration versus wrist block for analgesia after arthroscopy of the wrist
Authors: Agrawal Y. , Russon K. , Chakrabarti I. , Kocheta A. 
Published: September 2015

Wrist block has been used to provide pain relief for many procedures on the hand and wrist but its role in arthroscopy of the wrist remains unexplored. Chondrotoxicity has been a concern with the intra-articular infiltration of local anaesthetic. We aimed to evaluate and compare the analgesic effect of portal and wrist joint infiltration with a wrist block on the pain experienced by patients after arthroscopy of the wrist. A prospective, randomised, double-blind trial was designed and patients undergoing arthroscopy of the wrist under general anaesthesia as a day case were recruited for the study. Levo-bupivacaine was used for both techniques. The effects were evaluated using a ten-point visual analogue scale, and the use of analgesic agents was also compared. The primary outcomes for statistical analyses were the mean pain scores and the use of analgesia post-operatively. A total of 34 patients (63% females) were recruited to the portal and joint infiltration group and 32 patients (59% males) to the wrist block group. Mean age was 40.8 years in the first group and 39.7 years in the second group (p > 0.05). Both techniques provided effective pain relief in the first hour and 24 hours post-operatively but wrist block gave better pain scores at bedtime on the day of surgery (p = 0.007) and at 24 hours post-operatively (p = 0.006). Wrist block provides better and more reliable analgesia in patients undergoing arthroscopy of the wrist without exposing patients to the risk of chondrotoxicity. Cite this article: Bone Joint J 2015;97-B:1250–6.
Similar incidence of periprosthetic fluid collections after ceramic-on-polyethylene total hip arthroplasties and metal-on-metal resurfacing arthroplasties
Authors: Bisseling P. , de Wit B. W. K. , Hol A. M. , van Gorp M. J. , van Kampen A , van Susante J. L. C. 
Published: September 2015

Patients from a randomised trial on resurfacing hip arthroplasty (RHA) (n = 36, 19 males; median age 57 years, 24 to 65) comparing a conventional 28 mm metal-on-metal total hip arthroplasty (MoM THA) (n = 28, 17 males; median age 59 years, 37 to 65) and a matched control group of asymptomatic patients with a 32 mm ceramic-on-polyethylene (CoP) THA (n = 33, 18 males; median age 63 years, 38 to 71) were cross-sectionally screened with metal artefact reducing sequence-MRI (MARS-MRI) for pseudotumour formation at a median of 55 months (23 to 72) post-operatively. MRIs were scored by consensus according to three different classification systems for pseudotumour formation. Clinical scores were available for all patients and metal ion levels for MoM bearing patients. Periprosthetic lesions with a median volume of 16 mL (1.5 to 35.9) were diagnosed in six patients in the RHA group (17%), one in the MoM THA group (4%) and six in the CoP group (18%). The classification systems revealed no clear differences between the groups. Solid lesions (n = 3) were exclusively encountered in the RHA group. Two patients in the RHA group and one in the MoM THA group underwent a revision for pseudotumour formation. There was no statistically significant relationship between clinical scoring, metal ion levels and periprosthetic lesions in any of the groups. Periprosthetic fluid collections are seen on MARS-MRI after conventional CoP THA and RHA and may reflect a soft-tissue collection or effusion. Currently available MRI classification systems seem to score these collections as pseudotumours, causing an-overestimatation of the incidence of pseudotumours. Cite this article: Bone Joint J 2015;97-B:1175–82.
Femoroacetabular impingement osteoplasty
Authors: Loh B. W. , Stokes C. M. , Miller B. G. , Page R. S. 
Published: September 2015

There is an increased risk of fracture following osteoplasty of the femoral neck for cam-type femoroacetabular impingement (FAI). Resection of up to 30% of the anterolateral head–neck junction has previously been considered to be safe, however, iatrogenic fractures have been reported with resections within these limits. We re-evaluated the amount of safe resection at the anterolateral femoral head–neck junction using a biomechanically consistent model.In total, 28 composite bones were studied in four groups: control, 10% resection, 20% resection and 30% resection. An axial load was applied to the adducted and flexed femur. Peak load, deflection at time of fracture and energy to fracture were assessed using comparison groups.There was a marked difference in the mean peak load to fracture between the control group and the 10% resection group (p < 0.001). The control group also tolerated significantly more deflection before failure (p < 0.04). The mean peak load (p = 0.172), deflection (p = 0.547), and energy to fracture (p = 0.306) did not differ significantly between the 10%, 20%, and 30% resection groups.Any resection of the anterolateral quadrant of the femoral head–neck junction for FAI significantly reduces the load-bearing capacity of the proximal femur. After initial resection of cortical bone, there is no further relevant loss of stability regardless of the amount of trabecular bone resected.Based on our findings we recommend any patients who undergo anterolateral femoral head–neck junction osteoplasty should be advised to modify their post-operative routine until cortical remodelling occurs to minimise the subsequent fracture risk.Cite this article: Bone Joint J 2015;97-B:1214–19.
Cost–effectiveness of volar locking plate versus percutaneous fixation for distal radial fractures
Authors: Karantana A. , Scammell B. E. , Davis T. R. C. , Whynes D. K. 
Published: September 2015

This study compares the cost-effectiveness of treating dorsally displaced distal radial fractures with a volar locking plate and percutaneous fixation. It was performed from the perspective of the National Health Service (NHS) using data from a single-centre randomised controlled trial. In total 130 patients (18 to 73 years of age) with a dorsally displaced distal radial fracture were randomised to treatment with either a volar locking plate (n = 66) or percutaneous fixation (n = 64). The methodology was according to National Institute for Health and Care Excellence guidance for technology appraisals. . There were no significant differences in quality of life scores between groups at any time point in the study. Both groups returned to baseline one year post-operatively. NHS costs for the plate group were significantly higher (p < 0.001, 95% confidence interval 497 to 930). For an additional £713, fixation with a volar locking plate offered 0.0178 additional quality-adjusted life years in the year after surgery. The incremental cost-effectiveness ratio (ICER) for plate fixation relative to percutaneous fixation at list price was £40 068. When adjusting the prices of the implants for a 20% hospital discount, the ICER was £31 898. Patients who underwent plate fixation did not return to work earlier. We found no evidence to support the cost-effectiveness, from the perspective of the NHS, of fixation using a volar locking plate over percutaneous fixation for the operative treatment of a dorsally displaced radial fracture. Cite this article: Bone Joint J 2015;97-B:1264–70.
Life- and limb-threatening infections following the use of an external fixator
Authors: Jauregui J. J. , Bor N. , Thakral R. , Standard S. C. , Paley D. , Herzenberg J. E. 
Published: September 2015

External fixation is widely used in orthopaedic and trauma surgery. Infections around pin or wire sites, which are usually localised, non-invasive, and are easily managed, are common. Occasionally, more serious invasive complications such as necrotising fasciitis (NF) and toxic shock syndrome (TSS) may occur. We retrospectively reviewed all patients who underwent external fixation between 1997 and 2012 in our limb lengthening and reconstruction programme. A total of eight patients (seven female and one male) with a mean age of 20 years (5 to 45) in which pin/wire track infections became limb- or life-threatening were identified. Of these, four were due to TSS and four to NF. Their management is described. A satisfactory outcome was obtained with early diagnosis and aggressive medical and surgical treatment. Clinicians caring for patients who have external fixation and in whom infection has developed should be aware of the possibility of these more serious complications. Early diagnosis and aggressive treatment are required in order to obtain a satisfactory outcome. Cite this article: Bone Joint J 2015;97-B:1296–1300.