Search

Contains fulltext : 241226.pdf (Publisher’s version ) (Closed access) BACKGROUND: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0-1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. FINDINGS: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6-69·3) with olaparib and 64·5 months (63·4-68·7) with placebo. Median overall survival was 51·7 months (95% CI 41·5-59·1) with olaparib and 38·8 months (31·4-48·6) with placebo (hazard ratio 0·74 [95% CI 0·54-1·00]; p=0·054), unadjusted for the 38% of patients in the placebo group who received subsequent PARP inhibitor therapy. The most common grade 3 or worse treatment-emergent adverse event was anaemia (which occurred in 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in the placebo group). Serious treatment-emergent adverse events were reported in 50 (26%) of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo. Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the 195 patients receiving olaparib, six of which were judged to be treatment-related (attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]). INTERPRETATION: Olaparib provided a median overall survival benefit of 12·9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients. FUNDING: AstraZeneca and Merck.

A nurse leader-led evidence-based practice change.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published

OBJECTIVE To analyze changes by age-group in all-cause and cause-specific mortality rates from 2000–2011 in people with diabetes. RESEARCH DESIGN AND METHODS A total of 1,189,079 (7.3% with type 1 diabetes) Australians with diabetes registered on the National Diabetes Service Scheme between 2000 and 2011 were linked to the National Death Index. Mortality rates in the total population were age standardized to the 2001 Australian population. Mortality rates were calculated for the following age-groups: 0 to RESULTS For type 1 diabetes, all-cause, cardiovascular disease (CVD), and diabetes age-standardized mortality rates (ASMRs) decreased each year by 0.61, 0.35, and 0.14 per 1,000 person-years (PY), respectively, between 2000 and 2011, Ptrend < 0.05, while cancer mortality remained unchanged. By age, significant decreases in all-cause, CVD, and diabetes mortality rates were observed in all age-groups, excluding diabetes mortality in age-group 0–40 years. For type 2 diabetes, all-cause, CVD, and diabetes ASMRs decreased per year by 0.18, 0.15, and 0.03 per 1,000 PY, respectively, Ptrend < 0.001, while cancer remained unchanged. By age, these decreases were observed in all age-groups, excluding 0–40 years, where significant increases in all-cause and cancer mortality were noted and no change was seen for CVD and diabetes mortality. CONCLUSIONS All-cause, CVD, and diabetes ASMRs in type 1 and type 2 diabetes decreased between 2000 and 2011, while cancer ASMRs remained unchanged. However, younger populations are not benefiting from the same improvements as older populations. In addition, the absence of a decline in cancer mortality warrants urgent attention.

Figure 1. Hives After Shower. Ppractitioner. These patients are frequently diagnosed with contact dermatitis and given symptomatic treatment. Symptoms of contact dermatitis are treated frequently in the primary care setting, which makes an accurate diagnosis difficult. The list of differential diagnoses that are considered can be extensive and possibly lead to expensive testing and unnecessary referrals, lengthening the time until treatment success is obtained. Conducting a thorough history and physical can provide information that will insure a more timely diagnosis and management.

Background Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib. Methods This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Findings Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]; hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p

OBJECTIVE With improvements in cardiovascular disease (CVD) rates among people with diabetes, mortality rates may also be changing. However, these trends may be influenced by coding practices of CVD-related deaths on death certificates. We analyzed trends of mortality over 13 years in people with diabetes and quantified the potential misclassification of CVD mortality according to current coding methods. RESEARCH DESIGN AND METHODS A total of 1,136,617 Australians with diabetes registered on the National Diabetes Services Scheme between 1997 and 2010 were linked to the National Death Index. Excess mortality relative to the Australian population was reported as standardized mortality ratios (SMRs). Potential misclassification of CVD mortality was determined by coding CVD according to underlying cause of death (COD) and then after consideration of both the underlying and other causes listed in part I of the death certificate. RESULTS For type 1 diabetes, the SMR decreased in males from 4.20 in 1997 to 3.08 in 2010 (Ptrend < 0.001) and from 3.92 to 3.46 in females (Ptrend < 0.01). For type 2 diabetes, the SMR decreased in males from 1.40 to 1.21 (Ptrend < 0.001) and from 1.56 to 1.22 in females (Ptrend < 0.001). CVD deaths decreased from 35.6 to 31.2% and from 31.5 to 27.2% in males and females with type 1 diabetes, respectively (Ptrend < 0.001 for both sexes). For type 2 diabetes, CVD decreased from 44.5 to 29.2% in males and from 45.5 to 31.6% in females (Ptrend < 0.001 for both sexes). Using traditional coding methods, ∼38 and 26% of CVD deaths are underestimated in type 1 diabetes and type 2 diabetes, respectively. CONCLUSIONS All-cause and CVD mortality has decreased in diabetes. However, the total CVD mortality burden is underestimated when only underlying COD is considered. This has important ramifications for understanding mortality patterns in diabetes.

This article reports the outcomes of a sub-analysis of United Kingdom (UK) data collected during a noninterventional, cross-sectional study conducted in five European countries. The primary aim was to estimate the prevalence of cancer-related neuropathic pain (CRNP) in an outpatient sample of adult cancer patients visiting oncology clinics in the UK for standard care. Secondary aims were to report the nature and characteristics of the cancer and the pain in the patients with CRNP. This sub-analysis also assessed the usefulness of the PainDETECT screening tool as an aid for physicians in identifying the neuropathic component of cancer-related pain in daily practice. Based on physicians’ clinical judgment before reviewing the scores on the PainDETECT tool, the estimated number of outpatients with cancer experiencing chronic pain and considered to have CRNP was 104 of 195 patients (53.3%; 95% confidence interval [CI]: 46.3%- 60.3%). After reviewing patients’ scores on the tool, the estimate was 90 of 195 patients (46.2%; 95% CI: 39.2%-53.2%). Physicians changed from a positive (yes) to a negative (no) diagnosis of CRNP for 16 of 127 patients who had a low PainDETECT end score (

Purpose: To evaluate research on the vegetarian diet for its safety, effectiveness in reducing heart disease, special considerations, contraindications, and its association with decreased cardiovascular disease risk. Data sources: Selected research and evidence-based dietary guidelines found by searching CINAHL, PubMed, Ovid databases, and the World Wide Web. Conclusions: A carefully planned vegetarian diet with adequate supplementation may be effective for primary prevention of heart disease. The vegetarian diet is cost effective, safe, and relatively easy to implement. Implications for practice: Improved dietary choices can help improve many chronic conditions. Guidelines for proper nutrition within a vegetarian lifestyle are readily accessible to patients and professionals alike. Referral to a dietitian is an appropriate option in primary care settings.

The documented negative psychosocial effects of acne on self-esteem are significant. Acne is a common complaint among adolescents who present to family practice. Family nurse practitioners play a major role in the identification of acne, its effect on self-esteem, and proper treatment and referral. Both the adolescent and health care provider need to be aware that acne is a treatable skin condition. It is therefore essential that health care providers recognize and assess for the effects of acne on self-esteem and initiate treatment that could prevent permanent scarring—inside and out.

Objective: To investigate the enjoyment and perceived value associated with two interventions designed to reduce risk factors for eating disorders in young adolescents. Method: Participants were 86 high school students (53 boys and 33 girls) with a mean age of 13.4 years (SD=0.4). Classes were randomly assigned to either a control condition or one of the two intervention conditions, a media literacy program or a self-esteem program. Measures: Students in the intervention groups were asked to evaluate the two programs in terms of enjoyment and perceived value. Results: The majority of students thought that the programs were enjoyable and valuable. Overall, the media literacy program was the intervention preferred by students. Students in both interventions said that they had learnt to accept themselves better. Conclusions: Both programs seemed relevant in the process of helping students to be happier with themselves. When media literacy is delivered within an interactive, student-centred framework it may potentially be a safe and effective way of reducing risk factors for eating disorders. Differences in the enjoyment and value between the two interventions may be due to the different way in which the programs were implemented.

Of the total number of injuries treated at the Lewisham Hospital Sports Medicine Clinic (Sydney), over a period of eighteen months, lateral epicondylitis constitutes approximately 1.4%. The 36 patients this figure represents received varying treatments, which are listed below. The overall results were as follows.

With the recent passage of the Americans with Disabilities Act, the author conducted a study to determine what percentage of BSN nursing programs had a list of essential functions that students must be capable of performing while enrolled. Results showed that the majority of programs have not developed lists and currently do not request information, during the admissions process, related to the applicant's ability to complete the essential functions of the programs, with or without reasonable accomodation. Almost half of the programs surveyed plan to request this information during the admissions process in the future.

As more registered nurses (RNs) return to school to obtain a bachelor of science in nursing (BSN), innovative ways must be found to support them in this endeavor. Barriers for RNs who return to school include scheduling of coursework and fear of failure. One school of nursing with a traditional BSN program reviewed its RN-BSN track, with its low retention and graduation rates. With input from nursing leaders and nurses in the community, the school applied for and was awarded a 3-year Health Resources and Services Administration grant to redesign the RN-BSN program. A hybrid classroom-online curriculum is offered in a structured, sequential format so that the RNs are admitted once a year and must complete the courses as a group, in a cohort. Data collected from evaluations showed that program support, technology support, and social support from peers encouraged the RNs to “stay the course,” and 100% completed the requirements to graduate.

Objective This study compared the efficacy of a media literacy program and a self-esteem program designed to reduce general and specific risk factors for eating disorders. Method Four classes of 86 grade 8 students (53 boys and 33 girls), mean age of 13 years, were randomly assigned to either a control condition or one of the two intervention conditions. Assessment of general and specific risk factors was carried out at baseline, postintervention and 3-month follow-up. Results At postintervention the media literacy group had lower mean scores on weight concern than the control group (p =0.007) but the self-esteem group did not. There were some differences on self-esteem measures at the 3-month follow-up. Discussion Media literacy programs combined with an interactive, student-centered framework may potentially be a safe and effective way of reducing risk factors for eating disorders. The impact of teaching style needs to be further evaluated in prevention research. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 371–383, 2003.

Psychiatric nurses work in a variety of settings as supervisors, administrators, and consultants. They understand that success or failure of organizational activities depends in large measure on the staff's productivity, commitment, and cooperation. When these qualities are absent, major problems can ensue. This paper uses a case study approach to examine the impact that employees with borderline, obsessive-compulsive, and passive-aggressive personality disorders have on organizations. Specific disruptive behaviors that can challenge co-workers and negatively affect the effectiveness of the work group are presented. Therapeutic strategies are identified that have been adapted for use in the workplace. These strategies are used to help employees perform in a more effective manner while minimizing maladaptive responses to guidance and supervision.

There appear to be at least three growth factors for mouse BALB/c 3T3 cells in human milk. The purification of the predominant one is described in this chapter. Biochemical and immunological studies indicate that this growth factor is probably a form of human epidermal growth factor (EGF). Like EGF, the major human milk-derived growth factor has a molecular weight of about 6000, a pI of about 4.5, and is resistant to inactivation by dithiothreitol. (See this volume, Harper et al., for purification of human EGF.) In addition, Carpenter has shown that antibodies against human EGF will precipitate most of the growth factor activity for 3T3 cells found in human milk. The EGF-like species of growth factor cannot be detected in bovine milk. Instead, the major growth factor in bovine colostrum appears to be biochemically similar to platelet-derived growth factor (PDGF). Like PDGF, the bovine colostrum-derived growth factor has a molecular weight of about 30,000, a pI of about 10, is totally inactivated by dithiothreitol but is stable to treatments with guanidine-HCl, urea, and heat. Biochemical characterizations of milk-derived growth factors, EGF, and PDGF are summarized in Table III. At present, very little is known about the physiological role of these growth factors in milk. The availability of these growth factors in homogeneous form will facilitate the studies in understanding their possible involvement in the growth process.

The accident risk to the children of a random sample of 458 women living in a former Inner London borough was associated with both a working-class status and the presence of psychiatric disturbance (usually depression) in the mother. The time of onset of the psychiatric disorder in these women and in another sample of women treated for depression by psychiatrists and general practitioners indicates that the mother's psychiatric disorder greatly increases the risk of accidents to children.