Gaining momentum: New options and opportunities for the treatment of advanced melanoma.

Before 2011, patients with advanced or metastatic melanoma had a particularly poor long-term prognosis. Since traditional treatments failed to confer a survival benefit, patients were preferentially entered into clinical trials of investigational agents. A greater understanding of the epidemiology and biology of disease has underpinned the development of newer therapies, including six agents that have been approved in the EU, US and/or Japan: a cytotoxic T-lymphocyte antigen-4 inhibitor (ipilimumab), two programmed cell death-1 receptor inhibitors (nivolumab and pembrolizumab), two BRAF inhibitors (vemurafenib and dabrafenib) and a MEK inhibitor (trametinib). The availability of these treatments has greatly improved the outlook for patients with advanced melanoma; however, a major consideration for physicians is now to determine how best to integrate these agents into clinical practice. Therapeutic decisions are complicated by the need to consider patient and disease characteristics, and individual treatment goals, alongside the different efficacy and safety profiles of agents with varying mechanisms of action. Long-term survival, an outcome largely out of reach with traditional systemic therapies, is now a realistic goal, creating the additional need to re-establish how clinical benefit is evaluated. In this review we summarise the current treatment landscape in advanced melanoma and discuss the promise of agents still in development. We also speculate on the future of melanoma treatment and discuss how combination and sequencing approaches may be used to optimise patient care in the future.

Quelle prise en charge pour une suspicion de thrombose veineuse profonde des membres inférieurs [Suspicion of lower limb deep vein thrombosis: update on diagnosis and treatment].

Si l'examen clinique revêt une importance essentielle en lymphologie et exige des praticiens expérimentés, la lymphoscintigraphie et plus récemment la lympho-fluoroscopie au vert d'indocyanine constituent des moyens d'investigation précieux dans la prévention, le diagnostic et le traitement des pathologies vasculaires lymphatiques. L'intérêt de la lymphoscintigraphie réside dans l'analyse qualitative et quantitative de la migration des macromolécules par les vaisseaux lymphatiques et l'évaluation du secteur lymphatique profond. La lympho-fluoroscopie se distingue de la lymphoscintigraphie par l'obtention d'une cartographie détaillée des vaisseaux lymphatiques superficiels et d'images dynamiques en temps réel. Elle apporte à l'angiologue et au physiothérapeute des informations irremplaçables sur leur contractilité et la présence de dérivations compensatoires à privilégier lors du drainage lymphatique manuel. Venous thromboembolism is a frequent disease with an annual incidence of 0.75-2.69/1000 reaching 2-7/1000 > 70 years. Deep vein thrombosis (DVT) and pulmonary embolism are two manifestations of the same underlying disease. Most frequent localization of DVT is at lower limbs. The diagnostic workup begins with an estimation of DVT risk, a judicious use of D-Dimers, and compression venous ultrasound depending on DVT probability. The development of direct oral anticoagulants and recent data on interventional DVT treatment, in selected cases, have widened the therapeutic spectrum of DVT. The present article aims at informing the primary care physician of the optimized workup of patients with lower limb suspicion of DVT.

High Prevalence of Signs of Renal Damage Despite Normal Renal Function in a Cohort of HIV-Infected Patients: Evaluation of Associated Factors

Renal disorders are an emerging problem in HIV-infected patients. We performed a cross-sectional study of the first 1000 HIV-infected patients attended at our HIV unit who agreed to participate. We determined the frequency of renal alterations and its related risk factors. Summary statistics and logistic regression were applied. The study sample comprised 970 patients with complete data. Most were white (94%) and men (76%). Median (IQR) age was 48 (42–53) years. Hypertension was diagnosed in 19%, dyslipidemia in 27%, and diabetes mellitus in 3%. According to the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, 29 patients (3%) had an eGFR < 60 ml/min/1.73m2; 18 of them (62%) presented altered albumin/creatinine and protein/creatinine (UPC or UAC) ratios. Of the patients with eGFR> 60mL/min, it was present in 293 (30%), 38 of whom (7.1%) had UPC> 300mg/g. Increased risk of renal abnormalities was correlated with hypertension (OR, 1.821 [95%CI, 1.292;2.564]; p = 0.001), age (OR, 1.015 [95%CI, 1.001;1.030], per one year; p = 0.040), and use of tenofovir disoproxil fumarate (TDF) plus protease inhibitor (PI), (OR, 1.401 [95%CI, 1.078;1.821]; p = 0.012). Current CD4 cell count was a protective factor (OR, 0.9995 [95%CI, 0.9991;0.9999], per one cell; p = 0.035). A considerable proportion of patients presented altered UPC or UAC ratios, despite having an eGFR > 60mL/min. CD4 cell count was a protective factor; age, hypertension, and use of TDF plus PIs were risk factors for renal abnormalities. Based on our results, screen of renal abnormalities should be considered in all HIV-infected patients to detect these alterations early.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults.

QUESTIONS UNDER STUDY: As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS: We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS: A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS: There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

Free PAPP-A: a Novel Marker in Acute Coronary Syndrome Patients

In recent years, one important objective of cardiovascular research has been to find new markers that would improve the risk stratification and diagnosis of patients presenting with symptoms of acute coronary syndrome (ACS). Pregnancy-associated plasma protein A (PAPP-A) is a large metalloproteinase involved in insulin-like growth factor signalling. It is expressed in various tissues and seems to be involved in many physiological and pathological processes, such as folliculogenesis, bone formation, wound healing, pregnancy and atherosclerosis. The aim of this thesis was to investigate PAPP-A in ACS patients. Circulating concentrations of PAPP-A had been previously shown to be elevated in ACS. In this study it was revealed that the form of PAPP-A causing this elevation was the free noncomplexed PAPP-A. Thus, the form of PAPP-A in the circulation of ACS patients differed from the complexed PAPP-A form abundantly present in the circulation during pregnancy. A point-of-care method based on time-resolved immunofluorometric assays was developed, which enabled the rapid detection of free PAPP-A. The method was found to perform well with serum and heparin plasma samples as well as with heparinized whole blood samples. With this method the concentrations of free PAPP-A in healthy individuals were shown to be negligible. When the clinical performance of the method was evaluated with serum samples from ACS patients, it was shown that the free PAPP-A concentration in the admission sample was an independent predictor of myocardial infarction and death. Moreover, as a prognostic marker, free PAPP-A was revealed to be superior to total PAPPA, i.e. the combination of free and complexed PAPP-A, which has been measured by the other groups in this field. As heparin products are widely used as medication in ACS patients, the effect of heparin products on free PAPP-A molecule and circulating concentrations were also investigated in this study. It was shown that intravenous administration of low molecular weight or unfractionated heparin elicits a rapid release of free PAPP-A into the circulation in haemodialysis patients and patients undergoing angiography. Moreover, the interaction between PAPP-A and heparin was confirmed in gel filtration studies. Importantly, the patients included in the clinical evaluation of the free PAPP-A detection method developed had not received any heparin product medication before the admission sample and thus the results were not affected by the heparin effect. In conclusion, free PAPP-A was identified as a novel marker associated with ACS. The point-of-care methods developed enable rapid detection of this molecule which predicts adverse outcome when measured in the admission sample of ACS patients. However, the effect revealed of heparin products on circulating PAPP-A concentrations should be acknowledged when further studies are conducted related to free or total PAPP-A in ACS.

Immunohistochemical expression of HER-2/NEU-CERBB-2 in patients with adenocarcinoma of the stomach

OBJECTIVES: To determine the prevalence of Her-2/Neu-cerbb-2 in the gastric mucosa of patients with gastric adenocarcinoma in a brazilian patient group. METHODS: The immunohistochemical expression of Her-2/Neu was studied in 37 formalin-fixed paraffin-embedded tissue sections. RESULTS: The immunohistochemical reaction produced by the anti-HER-2/Neu antibody was positive in two cases (5.4%). CONCLUSION: The low prevalence of Her-2/Neu observed in these southern brazilian cases is probably due to the great number of poorly differentiated cancers in this serie.

Dialysis, time and death: comparisons of two consecutive decades among patients treated at the same Brazilian dialysis center

The survival of hemodialysis patients is likely to be influenced not only by well-known risk factors like age and comorbidity, but also by changes in dialysis technology and practices accumulated along time. We compared the survival curves, dialysis routines and some risk factors of two groups of patients admitted to a Brazilian maintenance hemodialysis program during two consecutive decades: March 1977 to December 1986 (group 1, N = 162) and January 1987 to June 1997 (group 2, N = 237). The median treatment time was 22 months (range 1-198). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank method. The Cox proportional hazard regression model was used to investigate the more important variables associated with outcome. The most important changes in dialysis routine and in patient care during the total period of observation were the progressive increase in the dose of dialysis delivered, the prohibition of potassium-free dialysate, the use of bicarbonate as a buffer and the upgrading of the dialysis equipment. There were no significant differences between the survival curves of the two groups. Survival rates at 1, 5 and 10 years were 84, 53 and 29%, respectively, for group 1 and 77, 42 and 21% for group 2. Patients in group 1 were younger (45.5 ± 15.2 vs 55.2 ± 15.9 years, P<0.001) and had a lower prevalence of diabetes (11.1 vs 27.4%, P<0.001) and of cardiovascular disease (9.3 vs 20.7%, P<0.001). According to the Cox multivariate model, only age (hazard ratio (HR) 1.04, confidence interval (CI) 1.03-1.05, P<0.001) and diabetes (HR 2.55, CI 1.82-3.58, P<0.001) were independent predictors of mortality for the whole group. Patients of group 2 had a lower prevalence of sudden death (19.1 vs 9.7%, P<0.001). After adjusting for age, diabetes and other mortality risk factors, the risk of death was 17% lower in group 2, although this difference was not statistically significant. We conclude that the negative effects of advanced age and of higher frequency of comorbidity on the survival of group 2 patients were probably offset by improvements in patient care and in the quality and dose of dialysis delivered, so that the survival curves did not undergo significant changes along time.

Skannausratkaisun ja yleisarkiston käyttöönotto potilasasiakirjojen käsittelyyn terveydenhuollossa

Julkinen terveydenhuolto on muutoksen ja monien haasteiden edessä, kun palveluiden kysyntä ja laatuvaatimukset kasvavat. Julkisen sektorin taloudellinen tilanne aiheuttaa paineita kustannusten pienentämiseksi ja toimintojen keskittämiseen. Muutoksista huolimatta terveydenhuollon henkilökunnalla tulee olla mahdollisimman helppo ja nopea pääsy potilasta koskeviin ajantasaisiin ja olennaisiin tietoihin. Tämä diplomityö tarkastelee tietojärjestelmän käyttöönottoprosessia, paperisten potilasasiakirjojen digitalisointia ja niiden hyödyntämistä hoitoprosessissa. Tutkimuksessa esitellään paperilähetteiden käsittely, skannausratkaisun käyttöönotto ja integrointi HUS:n XDS-yleisarkistoon. Tutkimuksen teoreettinen viitekehys koostuu käyttöönottoprosessista ja siihen liittyvistä haasteista, onnistumiseen vaikuttavista tekijöistä sekä onnistumiseen mittaamiseen käytettävissä olevista malleista ja mittareista. Tietojärjestelmän käyttöönoton onnistumiseen vaikutti erityisesti ennakkosuunnittelu ja muutosvastarinnan ymmärtäminen. Tietojärjestelmän käyttöönotossa havaittiin, että muutos hyväksytään käyttäjien osalta, kun se vastaa käyttäjien todelliseen tarpeeseen. Erityisesti lähetteiden käsittely sähköisessä muodossa koettiin hyödylliseksi ja tarpeelliseksi, koska tämä mahdollisti potilastietojen saatavuuden paikasta ja ajasta riippumatta ja tuki potilaan hoitoprosessia. Käyttöönotossa havaittiin, että skannausprosessi ei voi olla samanlainen kaikkialla, koska eri yksiköissä tapahtuva skannaus voi olla potilaskeskeistä tai asiakirjatyyppien mukaan tai kompeksista ja suuriin määriin perustuvaa.

Exercise may cause myocardial ischemia at the anaerobic threshold in cardiac rehabilitation programs

Myocardial ischemia may occur during an exercise session in cardiac rehabilitation programs. However, it has not been established whether it is elicited when exercise prescription is based on heart rate corresponding to the anaerobic threshold as measured by cardiopulmonary exercise testing. Our objective was to determine the incidence of myocardial ischemia in cardiac rehabilitation programs according to myocardial perfusion SPECT in exercise programs based on the anaerobic threshold. Thirty-nine patients (35 men and 4 women) diagnosed with coronary artery disease by coronary angiography and stress technetium-99m-sestamibi gated SPECT associated with a baseline cardiopulmonary exercise test were assessed. Ages ranged from 45 to 75 years. A second cardiopulmonary exercise test determined training intensity at the anaerobic threshold. Repeat gated-SPECT was obtained after a third cardiopulmonary exercise test at the prescribed workload and heart rate. Myocardial perfusion images were analyzed using a score system of 6.4 at rest, 13.9 at peak stress, and 10.7 during the prescribed exercise (P < 0.05). The presence of myocardial ischemia during exercise was defined as a difference ≥2 between the summed stress score and summed rest score. Accordingly, 25 (64%) patients were classified as ischemic and 14 (36%) as nonischemic. MIBI-SPECT showed myocardial ischemia during exercise within the anaerobic threshold. The 64% prevalence of ischemia observed in the study should not be looked on as representative of the whole population of patients undergoing exercise programs. Changes in patient care and exercise programs were implemented as a result of our finding of ischemia during the prescribed exercise.

Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Tehohoitopotilaan siirtotiedote hoitotyön päätöksenteon tukena - retrospektiivinen asiakirja-analyysi vuosilta 2001-2013

Tuija Lehtikunnas: Intensive care patient handover document in support of decision-making in nursing work - Retrospective document analysis for the period 2001–2013 University of Turku, Faculty of Medicine, Nursing Science Annales Universitatis Turkuensis Turku 2016 ABSTRACT The continuity of care and flow of information must be ensured when transferring the responsibility of care, whether this is done within an organisation or from one organisation to another. The purpose of this study was to describe and compare the nursing handover documents of long-term intensive care patients and changes to these documents during the years 2001–2013. Research data comprehended long-term intensive care patient handover documents (N = 250). Data was gathered from one university hospital intensive care unit and subjected to a content analysis of technical implementation, structure and content at five different time points. In addition to this, the nursing handover documents were analysed from a nursing decision-making standpoint. Sub-data (n = 5 x 50) from the years 2001, 2002, 2004, 2006 and 2013 was gathered. The first sub-data was manual, written on paper with a pen. The rest of the sub-data obtained was entered in a dedicated intensive care information system. The study developed an intensive care patient nursing handover document analysis framework, which was used to deductively analyse the research data. The results indicated that the transitioning to electronic records reinforced structure and identification improving the reusability of data was increased. Although intensive care nursing was recorded on nursing handover documents more comprehensively in more recent sub-data, it was done selectively with regard to overall patient care, e.g. there are no entries concerning the psychological support and counselling of patients or family members. Nursing handover documents do not contain a systematic description of the patient's communication and functional capacity at the moment of transfer. The patient's condition at the moment of transfer is not clearly indicated on the handover documents. Plans for follow-up treatment are not recorded at all. Nursing decision-making is difficult to find on the nursing handover documents used as research data. The study developed a handover document model for intensive care nursing that supports nursing decision-making and the continuity of care. Developmental recommendations focus on the management of co-operation within organisations for ensuring the continuity of care and enhancing each area of nursing in recording nursing handover documents by planning nursing for the patient, taking follow-up treatment resources into consideration. Keywords: Intensive care nursing, nursing decision-making, nursing records, information flow, nursing handover document, continuity of care

Reflective practice and the novice nurse /

The importance of reflective practice to the novice nurse was explored in this study. The novice nurse, for the purpose of this study, was defined as a Registered Nurse who graduated from an accredited nursing program within a 1 2-month period prior to the data collection date and who had no prior experience as a Registered Nurse before graduation. All of the nurses enrolled in this study were female. This study explored the perceived link between transformational learning and reflective practice, and whether there may be a need to standardize a conceptual framework and definition for reflective practice in nursing academia. The literature that was reviewed for this study indicated that there were inconsistencies in the application of reflective practice within academic curriculums. The literature did identify that the majority of academic scholars have agreed that reflection is paramount in the development of critical thinking skills, self-awareness, and selfdirection. And, while all of these skills drive professional practice and effect excellent patient care, institutional health care has been reticent to support the value of reflective practice because of a lack of empirical data sets. The 4 novice Registered Nurses who participated in this study were asked 4 openended questions that provided a foundation for comparing the novice nurses' experiences, interpretations, and perceptions of reflective practice. These nurses participated in individual audiotaped interviews with the researcher. The study was based upon Heath's (1998) model of "Theory hitegration via Reflective Practice." The results demonstrated that reflective practice was significant to the novice nurse and was used as a tool to identify further learning needs. Transformational learning through reflection was described by the study participants. The findings within this study are consistent with previous work done in the area of reflection and the novice nurse.

Management decision-making in nursing

This study developed a new, valid and reliable evaluation instrument to measure the level, type and pattern of management decisions of fifteen nursing students. The management decision score achieved using this instrument was correlated with two psychological determinants of management decision making: creativity and problem-solving ability. The instrument was a written patient management problem in case format, answered by a free form written response. The student responses were classified for type of management decision according to the sub-categories of technical, inter-personal, environmental and unique. Using statistical analysis a significant difference was found in the type of management decisions most frequently selected by the study sample. The students predominantly selected technical type decisions. This preference for one type of management decision may be due to a number of psychological and environmental factors. These factors may program and mold the type of management decisions student nurses make early in their career. Low but positive correlations were found between the total management score and the two psychological tests. This finding supports the authors cited in the literature who state that although creativity augments the type of management decision making, it is not present or encouraged widely in the nursing profession. These factors are worth considering when the profession becomes concerned over ritualization and lack of individuality in patient care. The tool is easy to administer, lends itself to a variety of professional settings and shows promise with further refinement for computer application.

Nurses' attitudes toward computers before and two months after training

This study examined nurses' attitudes toward computers before training and 2 months after training. A quantitative approach and a nonexperimental survey design were used in this study. Stronge and Brodt's (1985) instrument, Nurses' Attitudes Toward Computerization Questionnaire, was used to assess 27 nurses' attitudes prior to and 2 months after computer training. Demographic variables also were collected on the questionnaires. The results of this study showed that, overall, nurses had positive attitudes towards computers in both questionnaires. The results of the first questionnaire were consistent with other studies. There were no studies that involved a follow-up questionnaire using Stronge and Brodt's (1985) instrument. Attitude scores of Questionnaire 2 were higher than attitude scores of Questionnaire 1. More time for nursing tasks, less time for quality patient care, and threat to job security questions were found to be statistically significant. This study found no statistical significance between attitudes and demographic variables. Younger nurses a~d nurses with fewer years of computer experience were most likely to exhibit positive attitudes. Implications for practice and future research were discussed. Some limitations were identified and discussed.