Skin Cancer Education for Primary Care Physicians: A Systematic Review of Published Evaluated Interventions

BACKGROUND

Early detection of melanoma may provide an opportunity to positively impact melanoma mortality. Numerous skin cancer educational interventions have been developed for primary care physicians (PCPs) to improve diagnostic accuracy. Standardized training is also a prerequisite for formal testing of melanoma screening in the primary care setting.

OBJECTIVE

We conducted a systematic review to determine the extent of evaluated interventions designed to educate PCPs about skin cancer, including melanoma.

DESIGN

Relevant studies in the English language were identified through systemic searches performed in MEDLINE, EMBASE, BIOSIS, and Cochrane through December 2010. Supplementary information was obtained from corresponding authors of the included studies when necessary.

APPROACH

Studies eligible for inclusion formally evaluated skin cancer education interventions and were designed primarily for PCPs. Excluded studies lacked a specified training intervention, used decision-making software, focused solely on risk factor identification, or did not directly educate or assess participants. Twenty studies met the selection criteria. Data were extracted according to intervention content and delivery format, and study outcomes.

KEY RESULTS

All interventions included instructions about skin cancer diagnosis, but otherwise varied in content. Curricula utilized six distinct educational techniques, usually incorporating more than one. Intervention duration varied from 12 min to over 6 h. Eight of the 20 studies were randomized trials. Most studies (18/20, 90%) found a significant improvement in at least one of the following five outcome categories: knowledge, competence, confidence, diagnostic performance, or systems outcomes. Competence was most commonly measured; no study evaluated all categories. Variability in study design, interventions, and outcome measures prevented correlation of outcomes with intervention characteristics.

CONCLUSIONS

Despite the development of many isolated educational interventions, few have been tested rigorously or evaluated under sufficient standardized conditions to allow for quantitative comparison. Improved and rigorously tested skin cancer educational interventions for PCPs with outcome measures focusing on changes in performance are needed.     

Health-related quality of life in long term-survivors of thoracoabdominal aortic aneurysm repair.

The purpose was to assess health-related quality of life (HRQOL) in long-term survivors of thoracoabdominal aneurysm repair. Between 1983 and 2001, 43 patients underwent thoracoabdominal aneurysm repair. Long-term survivors (13) were investigated. Two were lost to follow-up. The mean follow-up period was 6.2 years. HRQOL was measured by Short Form (SF)-36, constructed of 36 items grouped into eight scales measuring physical functioning, role limitations caused by physical problems, bodily pain, general health perceptions, vitality, social functioning, role limitations caused by emotional problems, and mental health. Additional questions specific for vascular disease were ascribed. The patients' relatives received corresponding questions, responding on behalf of the patients. Patient data scores were compared with a selection of individuals from the general population. The patients' SF-36 scores were generally poorer than that of the healthy population in both physical and mental dimensions. Patients who had a complicated postoperative course generally scored lowest in physical dimensions. Comparing patients' scores with relatives scoring on behalf of the patients showed no statistical differences. According to disease-specific questions, impotence and pain were reported as major long-term postoperative problems. Patients with uncomplicated postoperative courses all reported improved health status (six) compared with the preoperative status, whereas five patients with complicated postoperative courses reported poorer health status. Nine of 11 patients experienced the same or improved HRQOL, and two patients reported reduced HRQOL after surgery. Ten of 11 patients evaluated the operation as successful. Although the sample size in this study is small, those who had postoperative complications or reported a decreased physical function in the years after surgery generally had low scores in almost all dimensions of the SF-36. When disease-specific questions were related to thoracoabdominal aneurysm surgery, most patients reported an acceptable HRQOL.     

Altered selectivity in an Arabidopsis metal transporter

Plants require metals for essential functions ranging from respiration to photosynthesis. These metals also contribute to the nutritional value of plants for both humans and livestock. Additionally, plants have the ability to accumulate nonessential metals such as cadmium and lead, and this ability could be harnessed to remove pollutant metals from the environment. Designing a transporter that specifically accumulates certain cations while excluding others has exciting applications in all of these areas. The Arabidopsis root membrane protein IRT1 is likely to be responsible for uptake of iron from the soil. Like other Fe(II) transporters identified to date, IRT1 transports a variety of other cations, including the essential metals zinc and manganese as well as the toxic metal cadmium. By heterologous expression in yeast, we show here that the replacement of a glutamic acid residue at position 103 in wild-type IRT1 with alanine increases the substrate specificity of the transporter by selectively eliminating its ability to transport zinc. Two other mutations, replacing the aspartic acid residues at either positions 100 or 136 with alanine, also increase IRT1 metal selectivity by eliminating transport of both iron and manganese. A number of other conserved residues in or near transmembrane domains appear to be essential for all transport function. Therefore, this study identifies at least some of the residues important for substrate selection and transport in a protein belonging to the ZIP gene family, a large transporter family found in a wide variety of organisms.     

Design,Organization and Management of a Controlled Population Screening Study for Detection of Colorectal Neoplasia: Attendance Rates in the NORCCAP Study (Norwegian Colorectal Cancer Prevention)

Background: In the past three decades, the incidence of colorectal cancer (CRC) in Norway has doubled, surpassing all other Nordic countries for both men and women to become the most frequently diagnosed cancer. A small-scale, randomized study on flexible sigmoidoscopy (FS) screening in Telemark, Norway, has shown a reduction in accumulated CRC incidence after 13 years. The aim of our study was to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy), and to test out the management and organization mimicking a countrywide screening service. A total of 13,823 men and women (1:1), age 55-64 years, were drawn randomly from the population registries in Oslo (urban) and the county of Telemark (mixed urban and rural) and invited to have a screening examination. The rest of the relevant age cohorts constituted the control groups. In the screening group, 535 individuals were excluded according to exclusion criteria, rendering 13,288 individuals eligible for screening examination. Methods: A once only screening model was used. In the screening group, individuals were randomized to have a once only FS or a combination of FS and faecal occult blood test (FOBT). Results: The overall attendance rate was 8,849 out of 13,288 (67%); 73% in Telemark and 60% in Oslo. Attendance for FS only was 68% and 65% for combined FS&FOBT. Conclusions: The present FS/FS&FOBT screening study obtained a high acceptance rate for both screening modalities. The attendance rate was stable throughout the trial, suggesting an acceptable model for management of future countrywide screening.     

Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins

The rapidly growing recognition of the role of oncogenic ROS1 fusion proteins in the malignant transformation of multiple cancers, including lung adenocarcinoma, cholangiocarcinoma, and glioblastoma, is driving efforts to develop effective ROS1 inhibitors for use as molecularly targeted therapy. Using a multidisciplinary approach involving small molecule screening in combination with in vitro and in vivo tumor models, we show that foretinib (GSK1363089) is a more potent ROS1 inhibitor than crizotinib (PF-02341066), an ALK/ROS inhibitor currently in clinical evaluation for lung cancer patients harboring ROS1 rearrangements. Whereas crizotinib has demonstrated promising early results in patients with ROS1-rearranged non–small-cell lung carcinoma, recently emerging clinical evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in the kinase domain of ROS1, thus necessitating identification of additional potent ROS1 inhibitors for therapeutic intervention. We confirm that the ROS1^G2032R mutant, recently reported in clinical resistance to crizotinib, retains foretinib sensitivity at concentrations below safe, clinically achievable levels. Furthermore, we use an accelerated mutagenesis screen to preemptively identify mutations in the ROS1 kinase domain that confer resistance to crizotinib and demonstrate that these mutants also remain foretinib sensitive. Taken together, our data strongly suggest that foretinib is a highly effective ROS1 inhibitor, and further clinical investigation to evaluate its potential therapeutic benefit for patients with ROS1-driven malignancies is warranted.Receptor tyrosine kinases (RTKs) are critical mediators of extracellular signals that control key cell growth, survival, and motility pathways. Conversely, deregulated and constitutive RTK activation is responsible for the initiation and progression of many cancers. Multiple mechanisms contribute to aberrant RTK activation including chromosomal rearrangements, point mutations, and gene amplification. Oncogenic activation of the orphan RTK c-ros oncogene 1 (ROS1) is observed in a subset of patients with glioblastoma, non–small-cell lung cancer (NSCLC), and cholangiocarcinoma (1–5). In most cases, ROS1 signaling is activated by interchromosomal translocation or intrachromosomal deletion that results in N-terminal ROS1 fusion genes. Several ROS1 kinase fusion proteins have been identified, including the Fused in Glioblastoma–ROS1 (FIG–ROS) that was first discovered in a human glioblastoma cell line (2) and more recently in patients with NSCLC (4), cholangiocarcinoma (3), and serous ovarian carcinoma (6). The SLC34A2–ROS1 (SLC–ROS) fusion is present in a subset of patients with NSCLC (1, 7) and gastric cancer (8). Other ROS1 fusions include CD74–ROS1, EZR–ROS1, LRIG3–ROS1, SDC4–ROS1, and TPM3–ROS1 (5).Given the recent success of molecularly targeted therapies in treating cancers driven by oncogenic kinases, there is acute clinical momentum to identify inhibitors that selectively target ROS1 fusions. Because the ROS1 and Anaplastic Lymphoma Kinase (ALK) domains are partially homologous, the Food and Drug Administration (FDA)-approved ALK/MET kinase inhibitor crizotinib is being investigated via phase I/II clinical trials for its efficacy in ROS1-driven lung cancer patients (9). Although early results appear promising, consistent with the clinical experience of crizotinib in patients with ALK-positive lung cancer to date, as well as prior experience with kinase inhibitors in many other malignancies (10–13), recent evidence suggests that a subset of patients with crizotinib-treated ROS1 fusion-positive may acquire ROS1 kinase domain mutations that confer drug resistance, thus necessitating alternative therapeutic approaches.To identify additional and potentially more efficacious ROS1 inhibitors, we used an unbiased, high-throughput kinase inhibitor screening assay and discovered that foretinib (GSK1363089) and Gö6976 are potent inhibitors of ROS1. Foretinib selectively suppresses the growth of the SLC–ROS-driven human NSCLC cell line HCC78 and of FIG–ROS-driven murine cholangiocarcinoma, but not of EGFR-driven NSCLC or phosphatase and tensin homolog (PTEN)-suppressed murine cholangiocarcinoma cells. Further, treatment of tumor-bearing mice with foretinib resulted in specific and dramatic regression of FIG–ROS-driven tumors in contrast to non-FIG–ROS tumors that share similar histopathological features. Importantly, we also use a cell-based in vitro resistance screen to preemptively identify several ROS1 kinase domain point mutations that confer resistance to crizotinib and show that these crizotinib-resistant ROS1 mutants remain sensitive to foretinib. These data suggest that foretinib may provide an alternative front-line treatment for ROS1-positive tumors and an effective second-line approach for patients that develop crizotinib-resistant disease.     

Increased arterial adrenaline is related to pain in uncomplicated myocardial infarction

Plasma levels of catecholamines, beta-thromboglobulin (BTG) and arginine vasopressin (AVP), and degree of pain were examined in 22 patients with suspected uncomplicated myocardial infarction within 24 h following onset of chest pain. Sixteen patients developed infarction with peak creatine phosphokinase at 1280 Ul-1 (range 293-3770 Ul-1). Fifteen healthy men served as controls (C). Arterial adrenaline levels were significantly higher in patients with pain (1.15 +/- 0.23 nmol l-1, n = 8, mean value +/- SEM) than in those without pain (0.60 +/- 0.10 nmol l-1, n = 14, P less than 0.05). Plasma catecholamines were moderately but significantly elevated in myocardial infarction; the concentration of arterial adrenaline was 0.83 +/- 0.14 nmol l-1 and that of arterial noradrenaline was 2.70 +/- 0.28 nmol l-1 compared with 0.44 +/- 0.04 nmol l-1 (P less than 0.025) and 1.47 +/- 0.05 nmol l-1 (P less than 0.0005), respectively, in C. One week later, plasma catecholamines had returned to baseline levels. Plasma BTG showed borderline elevation (1.0 +/- 0.1 pmol l-1) compared with C (0.6 +/- 0.1 pmol l-1, P = 0.04), and remained unchanged 1 week later. Plasma AVP was at baseline level. Uncomplicated myocardial infarction, regardless of size, was associated with only moderately increased sympathetic tone. Plasma adrenaline was related more to the degree of pain than to the presence of acute myocardial infarction. Arterial adrenaline may be a sensitive marker of sympatho-adrenal activity related to pain.     

Oligodendroglioma. Histologic evaluation and prognosis

All oligodendrogliomas registered in Norway during a 25-year period (1953-1977) were studied to establish the frequency of different histologic features and to compare them with survival data of the patients. The minimum observation time was five years. The original tumor specimens from 208 patients were independently reexamined by two pathologists. The characteristic oligodendroglioma of this series was of medium cell density (53% of lesions), with moderate nuclear atypia, with vascular endothelial proliferation (53%), calcification (56%), with from one to five mitotic figures per ten high power fields, and without microcystic degenerative changes (58%). Subpial tumor cell infiltration, perivascular lymphocytic infiltration and local leptomeningeal invasion were present in a minority of cases. In 11 cases autopsy material was the only source of diagnosis. Microcysts, necrosis, and cell density were the only histologic features of prognostic significance. Subpial infiltrative growth was of suggestive prognostic value. There was no significant association between the number of mitotic figures and survival. Vascular endothelial proliferation, calcification, pronounced nuclear atypia, perivascular lymphocytic infiltration and local leptomeningeal invasion were of no significant prognostic value. Age at operation did not alter these conclusions, neither did sex nor duration of preoperative symptoms.     

The prognostic value of Laurén's histopathological classification system and ABO blood groups in patients with stomach carcinoma

The prognostic value of Laurén's histopathological classification system and the ABO blood group system has been studied in 275 patients with cancer of the stomach. The study disclosed a higher rate of tumours of intestinal type in females aged 70 years or more compared with those under 70 years, but no such relation for males. We found no relation between histopathological classification and blood groups. For patients with blood group A the 5-year survival was 17.5%, compared to 8.4% for blood group O (P less than 0.05). Survival for patients with intestinal and diffuse tumours was 17.7% and 4.8% respectively (P less than 0.01). A multivariate analysis showed that the histopathological classification system, independently, was an important factor with respect to survival (all other factors constant). Blood group might also be of importance as a prognostic factor, but further studies are necessary to confirm this.     

Nurse leaders' views on clinical ladders as a strategy in professional development

AIM: To investigate nurse leaders' views on clinical ladders as a strategy in professional development of nursing. BACKGROUND: Hospitals worldwide have implemented clinical ladders to boost professional development and improve quality of patient care. At ward level good leadership is vital in creating a learning environment and using nurses' new competence. METHOD: The design was explorative and data were collected in focus groups with 19 nurse leaders at the ward level and 24 executive nurse leaders at hospitals with several years of experience with clinical ladders. RESULTS: Most nurse leaders did not think strategically in promoting clinical ladders at the organizational level. Nurse leaders who considered clinical ladders a tool in developing nursing quality found motivational work challenging and rewarding. Not all nurse leaders managed to utilize clinical specialists' new competence. CONCLUSION: Further investigation into nurse leaders' actions as strategic managers of development and use of nurses' competence is warranted. Implications for nursing management It is important that managers see the close connection between professional development of individuals and development of quality and high standard in the ward. A prerequisite is therefore to engage in the strategic planning of competence at all levels of decision in the organization.