An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation

Objectives This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses.
Design and setting Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions.
Participants Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients’ PCPs and cancer treatment specialists (CTSs) are surveyed, and ‘data rules’ are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases.
Main outcomes Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types.
Conclusion An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials.
Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules.
Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma.
Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly.

EULAR Recommendations for Women's Health and the Management of Family Planning, Assisted Reproduction, Pregnancy and Menopause in Patients with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

DATA DRIVEN APPROACHES TO IDENTIFY DETERMINANTS OF HEART DISEASES AND CANCER RESISTANCE

Cancer and cardio-vascular diseases are the leading causes of death world-wide. Caused by systemic genetic and molecular disruptions in cells, these disorders are the manifestation of profound disturbance of normal cellular homeostasis. People suffering or at high risk for these disorders need early diagnosis and personalized therapeutic intervention. Successful implementation of such clinical measures can significantly improve global health. However, development of effective therapies is hindered by the challenges in identifying genetic and molecular determinants of the onset of diseases; and in cases where therapies already exist, the main challenge is to identify molecular determinants that drive resistance to the therapies. Due to the progress in sequencing technologies, the access to a large genome-wide biological data is now extended far beyond few experimental labs to the global research community. The unprecedented availability of the data has revolutionized the capabilities of computational researchers, enabling them to collaboratively address the long standing problems from many different perspectives. Likewise, this thesis tackles the two main public health related challenges using data driven approaches. Numerous association studies have been proposed to identify genomic variants that determine disease. However, their clinical utility remains limited due to their inability to distinguish causal variants from associated variants. In the presented thesis, we first propose a simple scheme that improves association studies in supervised fashion and has shown its applicability in identifying genomic regulatory variants associated with hypertension. Next, we propose a coupled Bayesian regression approach -- eQTeL, which leverages epigenetic data to estimate regulatory and gene interaction potential, and identifies combinations of regulatory genomic variants that explain the gene expression variance. On human heart data, eQTeL not only explains a significantly greater proportion of expression variance in samples, but also predicts gene expression more accurately than other methods. We demonstrate that eQTeL accurately detects causal regulatory SNPs by simulation, particularly those with small effect sizes. Using various functional data, we show that SNPs detected by eQTeL are enriched for allele-specific protein binding and histone modifications, which potentially disrupt binding of core cardiac transcription factors and are spatially proximal to their target. eQTeL SNPs capture a substantial proportion of genetic determinants of expression variance and we estimate that 58% of these SNPs are putatively causal. The challenge of identifying molecular determinants of cancer resistance so far could only be dealt with labor intensive and costly experimental studies, and in case of experimental drugs such studies are infeasible. Here we take a fundamentally different data driven approach to understand the evolving landscape of emerging resistance. We introduce a novel class of genetic interactions termed synthetic rescues (SR) in cancer, which denotes a functional interaction between two genes where a change in the activity of one vulnerable gene (which may be a target of a cancer drug) is lethal, but subsequently altered activity of its partner rescuer gene restores cell viability. Next we describe a comprehensive computational framework --termed INCISOR-- for identifying SR underlying cancer resistance. Applying INCISOR to mine The Cancer Genome Atlas (TCGA), a large collection of cancer patient data, we identified the first pan-cancer SR networks, composed of interactions common to many cancer types. We experimentally test and validate a subset of these interactions involving the master regulator gene mTOR. We find that rescuer genes become increasingly activated as breast cancer progresses, testifying to pervasive ongoing rescue processes. We show that SRs can be utilized to successfully predict patients' survival and response to the majority of current cancer drugs, and importantly, for predicting the emergence of drug resistance from the initial tumor biopsy. Our analysis suggests a potential new strategy for enhancing the effectiveness of existing cancer therapies by targeting their rescuer genes to counteract resistance. The thesis provides statistical frameworks that can harness ever increasing high throughput genomic data to address challenges in determining the molecular underpinnings of hypertension, cardiovascular disease and cancer resistance. We discover novel molecular mechanistic insights that will advance the progress in early disease prevention and personalized therapeutics. Our analyses sheds light on the fundamental biological understanding of gene regulation and interaction, and opens up exciting avenues of translational applications in risk prediction and therapeutics.

An investigation of the clinical utility of preoperative cardiopulmonary exercise testing in patients undergoing major pancreatic surgery

Pancreaticoduodenectomy with or without adjuvant chemotherapy remains the only modality of possible cure in patients with cancer involving the head of the pancreas and the periampullary region. While mortality rates after pancreaticoduodenectomy have improved considerably over the course of the last century, morbidity remains high. Patient selection is of paramount importance in ensuring that major surgery is offered to individuals who will most benefit from a pancreaticoduodenectomy. Moreover, identifying preoperative risk factors provides potential targets for prehabilitation and optimisation of the patient's physiology before undertaking surgery. In addition to this, early identification of patients who are likely to develop postoperative complications allows for better allocation of critical care resources and more aggressive management high risk patients. Cardiopulmonary exercise testing is becoming an increasingly popular tool in the preoperative risk assessment of the surgical patient. However, very little work has been done to investigate the role of cardiopulmonary exercise testing in predicting complications after pancreaticoduodenectomy. The impact of jaundice, systemic inflammation and other preoperative clinicopathological characteristics on cardiopulmonary exercise physiology has not been studied in detail before in this cohort of patients. The overall aim of the thesis was to examine the relationships between preoperative clinico-pathological characteristics including cardiopulmonary exercise physiology, obstructive jaundice, body composition and systemic inflammation and complications and the post-surgical systemic inflammatory response in patients undergoing pancreaticoduodenectomy. Chapter 1 reviews the existing literature on preoperative cardiopulmonary exercise testing, the impact of obstructive jaundice, perioperative systemic inflammation and the importance of body composition in determining outcomes in patients undergoing major surgery with particular reference to pancreatic surgery. Chapter 2 reports on the role of cardiopulmonary exercise testing in predicting postoperative complications after pancreaticoduodenectomy. The results demonstrate that patients with V˙O2AT less than 10 ml/kg/min are more likely to develop a postoperative pancreatic fistula, stay longer in hospital and less likely to receive adjuvant therapy. These results emphasise the importance of aerobic fitness to recover from the operative stress of major surgery without significant morbidity. Cardiopulmonary exercise testing may prove useful in selecting patients for intensive prehabilitation programmes as well as for other optimisation measures to prepare them for major surgery. Chapter 3 evaluates the relationship between cardiopulmonary exercise physiology and other clinicopathological characteristics of the patient. A detailed analysis of cardiopulmonary exercise test parameters in jaundiced versus non-jaundiced patients demonstrates that obstructive jaundice does not impair cardiopulmonary exercise physiology. This further supports emerging evidence in contemporary literature that jaundiced patients can proceed directly to surgery without preoperative biliary drainage. The results of this study also show an interesting inverse relationship between body mass index and anaerobic threshold which is analysed in more detail in Chapter 4. Chapter 4 examines the relationship between preoperative cardiopulmonary exercise physiology and body composition in depth. All parameters measured at cardiopulmonary exercise test are compared against body composition and body mass index. The results of this chapter report that the current method of reporting V˙O2, both at peak exercise and anaerobic threshold, is biased against obese subjects and advises caution in the interpretation of cardiopulmonary exercise test results in patients with a high BMI. This is particularly important as current evidence in literature suggests that postoperative outcomes in obese subjects are comparable to non-obese subjects while cardiopulmonary exercise test results are also abnormally low in this very same cohort of patients. Chapter 5 analyses the relationship between preoperative clinico-pathological characteristics including systemic inflammation and the magnitude of the postoperative systemic inflammatory response. Obstructive jaundice appears to have an immunosuppressive effect while elevated preoperative CRP and hypoalbuminemia appear to have opposite effects with hypoalbuminemia resulting in a lower response while elevated CRP in the absence of hypoalbuminemia resulted in a greater postoperative systemic inflammatory response. Chapter 6 evaluates the role of the early postoperative systemic inflammatory response in predicting complications after pancreaticoduodenectomy and aims to establish clinically relevant thresholds for C-Reactive Protein for the prediction of complications. The results of this chapter demonstrate that CRP levels as early as the second postoperative day are associated with complications. While post-operative CRP was useful in the prediction of infective complications, this was the case only in patients who did not develop a post-operative pancreatic fistula. The predictive ability of inflammatory markers for infectious complications was blunted in patients with a pancreatic fistula. Chapter 7 summarises the findings of this thesis, their place in current literature and future directions. The results of this thesis add to the current knowledge regarding the complex pathophysiological abnormalities in patients undergoing pancreaticoduodenectomy, with specific emphasis on the interaction between cardiopulmonary exercise physiology, obstructive jaundice, systemic inflammation and postoperative outcomes. The work presented in this thesis lays the foundations for further studies aimed at improving outcomes after pancreaticoduodenectomy through the development of individualised, goal-directed therapies that are initiated well before this morbid yet necessary operation is performed.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting.

Cancer appetite and symptom questionnaire (CASQ) for brazilian patients: Cross-cultural adaptation and validation study

Background: Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods: This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2/df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results: Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2/df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). The model exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2: λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2: λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2: λ: p = .058; i: p < .001; Res: p < .001). Conclusion: The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatments.

Assessment of Epstein-Barr virus nucleic acids in gastric but not in breast cancer by next-generation sequencing of pooled Mexican samples

Gastric (GC) and breast (BrC) cancer are two of the most common and deadly tumours. Different lines of evidence suggest a possible causative role of viral infections for both GC and BrC. Wide genome sequencing (WGS) technologies allow searching for viral agents in tissues of patients with cancer. These technologies have already contributed to establish virus-cancer associations as well as to discovery new tumour viruses. The objective of this study was to document possible associations of viral infection with GC and BrC in Mexican patients. In order to gain idea about cost effective conditions of experimental sequencing, we first carried out an in silico simulation of WGS. The next-generation-platform IlluminaGallx was then used to sequence GC and BrC tumour samples. While we did not find viral sequences in tissues from BrC patients, multiple reads matching Epstein-Barr virus (EBV) sequences were found in GC tissues. An end-point polymerase chain reaction confirmed an enrichment of EBV sequences in one of the GC samples sequenced, validating the next-generation sequencing-bioinformatics pipeline.

Evaluation of two instruments of perceived symptom intensity in palliative care patients in an outpatient clinic

AIMS AND OBJECTIVES: To evaluate the test-retest stability in assessments of perceived symptom intensity on the Edmonton Symptom Assessment System-revised and the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative. The possible interchangeability between the instruments and the patients' experiences of completing the instruments were also studied. BACKGROUND: The two instruments assess the same symptoms, but the symptom intensity is assessed on 11-point numerical scales on the Edmonton Symptom Assessment System-revised and on four-point verbal descriptive scales on the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative. Both instruments are commonly used; however, uncertainty exists about which instrument should be recommended and about the interchangeability of the instruments. DESIGN: This study used a test-retest design with inter-scale comparisons. METHODS: Data from 54 patients with cancer who were receiving palliative care in an oncology outpatient clinic were self-reported by the patients in the clinic, at home and when patients returned to the clinic. RESULTS: The assessments on the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative verbal rating scales showed a higher level of test-retest stability than the assessments on the Edmonton Symptom Assessment System-revised numerical scoring scales, indicating higher reliability. The correspondence between the verbal categories and the numerical scores of symptom intensity were low because different verbal categories were used by patients who assessed the same numerical score. CONCLUSIONS: The test-retest stability in the assessments was higher on the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative and the results show that assessments on the two instruments could not be used interchangeably. Therefore, the symptom instrument chosen must be specified and unchanged within a patient to improve efficacy in clinical practice. RELEVANCE TO CLINICAL PRACTICE: The Edmonton Symptom Assessment System-revised or the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core 15 Palliative can be used for initial assessments of patients, but should not be compared or used interchangeably. It is vitally important to have individual follow-up for all patients who score an instrument.

A systematic review of the impact of weight loss on cancer incidence and mortality

Obesity is well recognized as a significant risk factor for certain cancers; however, a corresponding risk reduction with weight loss is not yet clearly defined. This review aims to examine the literature investigating the effect of all types of weight loss on cancer incidence and mortality, and to more clearly describe the relationship between these two factors. A literature search identified 34 publications reporting weight loss data in relation to cancer incidence or mortality. All except one were observational studies and the majority used self-reported weights and did not define intentionality of weight loss. 16/34 studies found a significant inverse association between weight loss and cancer incidence or mortality. The remainder returned null findings. The observed association was more consistently seen in studies that investigated the effect of intentional weight loss (5/6 studies) and the risk reduction was greatest for obesity-related cancers and in women. In conclusion, intentional weight loss does result in a decreased incidence of cancer, particularly female obesity-related cancers. However, there is a need for further evaluation of sustained intentional weight loss in the obese with less reliance on self-reported weight data and more focus on male populations.

Comparison of patient-reported need of psycho-oncologic support and the doctor's perspective: how do they relate to disease severity in melanoma patients?

Objective: Psycho-neuro-immune research suggests an association between cancer outcomes and psychosocial distress. Objective criteria to determine patients’ levels of distress are important to establish potential links to disease outcomes. Methods: We compared three patient-reported with one doctor-reported measures of psychooncologic distress frequently used in routine cancer care and investigated associations with standard disease severity parameters in melanoma patients. We enrolled n = 361 patients, successively seen at two outpatient university clinics in Germany. In the naturalistic study, n = 222 patients had been diagnosed <180 days and were seen for the first time (Group I); n = 139 had been diagnosed >180 days and were in after-care (Group II). Results: Across groups, only moderate associations were seen between patient- reported and doctorreported measures. Regarding clinical variables, disease severity and perceived need of psychooncologic support reported by patients or doctors showed hardly any association. After subgroup stratification, in patients of Group II, patient-reported and doctor-reported instruments showed some small associations with disease parameters commonly linked to more rapid cancer progression in patients who are in cancer after-care. Conclusions: Overall, the few and low associations suggest that need of psycho-oncologic support and clinical variables were largely independent of each other and doctors’ perception may not reflect the patient’s view. Therefore, the assessment of the patient perspective is indispensable to ensure that melanoma patients receive appropriate support, as such need cannot be derived from other disease parameters or proxy report. More research is needed applying psychometrically robust instruments that are ideally combined with sensitive biomarkers to disentangle psycho-neuro-immune implications in melanoma patients.

Heart failure following cancer therapy in patients with hematological malignancies aged 18 years and under : a linked health data analysis (1996-2009)

Introduction: The causal link between chemotherapy treatments and subsequent cardiotoxicity is well established, particularly for children with hematological malignancies. Little information exists on the characteristics and outcomes for patients with heart failure (HF) after chemotherapy. This study aimed to describe the characteristics, survival and mortality of patients who received chemotherapy for hematological cancer (leukemias, lymphomas and related disorders) before 18 years old and subsequently developed HF compared to those who did not.

Methods: Linked health data (1996-2009) from the Queensland Cancer Registry, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. From all breast and hematological cancers patients (n=73,158), 15,987 received chemotherapy, including 819 patients aged ≤18 years at time of cancer diagnosis. Patients were categorized as those with an index HF admission (occurred after cancer diagnosis) and those without an index HF admission (non HF).

Results: Of the 819 patients, 3.7% (n=30) had an index HF admission. Median age of HF patients at time of cancer diagnosis was 5 years (IQR 3-12) compared to 7 years (IQR 3-14) in the non HF group (p=0.503). Median follow up from cancer diagnosis was 2.5 years in the HF group compared to 5.42 years in the non HF group (p<0.01). Of those who developed HF, 70% (n=21) had the index admission within 12 months of their cancer diagnosis. Of those with HF, 53.3% (n=16) died (all cause) compared to 14.6% (n=115) with no HF. On adjustment for age, sex and chemotherapy admissions, HF patients had an almost 5 fold increased mortality risk compared to non HF patients (HR 4.91 [95% CI, 2.88-8.36]) (Figure 1).

Conclusions: This study demonstrated that in children with hematological cancers the onset of HF occurred soon after chemotherapy and mortality risk is almost 5 times that of children who do not develop HF. Innovative strategies are still needed for the prevention and management of cardiotoxicity in this population.

A randomized controlled trial of a nurse-led supportive care package (SurvivorCare) for survivors of colorectal cancer

INTRODUCTION: Colorectal cancer (CRC) and its treatments can cause distressing sequelae. We conducted a multicenter randomized controlled trial aiming to improve psychological distress, supportive care needs (SCNs), and quality of life (QOL) of patients with CRC. The intervention, called SurvivorCare (SC), comprised educational materials, needs assessment, survivorship care plan, end-of-treatment session, and three follow-up telephone calls.

METHODS: At the end of treatment for stage I-III CRC, eligible patients were randomized 1:1 to usual care (UC) or to UC plus SC. Distress (Brief Symptom Inventory 18), SCNs (Cancer Survivors' Unmet Needs measure), and QOL (European Organization for Research and Treatment of Cancer [EORTC] QOL questionnaires C30 and EORTC CRC module CR29) were assessed at baseline and at 2 and 6 months (follow-up 1 [FU1] and FU2, respectively). The primary hypothesis was that SC would have a beneficial effect on distress at FU1. The secondary hypotheses were that SC would have a beneficial effect on (a) SCN and QOL at FU1 and on (b) distress, SCNs, and QOL at FU2. A total of 15 items assessed experience of care.

RESULTS: Of 221 patients randomly assigned, 4 were ineligible for the study and 1 was lost to FU, leaving 110 in the UC group and 106 in the SC group. Patients' characteristics included the following: median age, 64 years; men, 52%; colon cancer, 56%; rectal cancer, 35%; overlapping sites of disease, 10%; stage I disease, 7%; stage II, 22%; stage III, 71%. Baseline distress and QOL scores were similar to population norms. Between-group differences in distress at FU1 (primary outcome) and at FU2, and SCNs and QOL at FU1 and FU2 were small and nonsignificant. Patients in the SC group were more satisfied with survivorship care than those in the UC group (significant differences on 10 of 15 items).

CONCLUSION: The addition of SC to UC did not have a beneficial effect on distress, SCNs, or QOL outcomes, but patients in the SC group were more satisfied with care.

IMPLICATIONS FOR PRACTICE: Some survivors of colorectal cancer report distressing effects after completing treatment. Strategies to identify and respond to survivors' issues are needed. In a randomized controlled trial, the addition of a nurse-led supportive care package (SurvivorCare) to usual posttreatment care did not impact survivors' distress, quality of life, or unmet needs. However, patients receiving the SurvivorCare intervention were more satisfied with survivorship care. Factors for consideration in the design of subsequent studies are discussed.

The catheter to vein ratio and rates of symptomatic venous thromboembolism in patients with a peripherally inserted central catheter (PICC): a prospective cohort study.

BACKGROUND: Peripherally inserted central catheters (PICCs) are a common vascular access device used in clinical practice. Their use may be complicated by adverse events such as venous thromboembolism (VTE). The size of the vein used for PICC insertion and thus the catheter to vein ratio is thought to be a controllable factor in the reduction of VTE rates in patients who have a PICC. However, an optimal catheter to vein ratio for PICC insertion has not previously been investigated to inform clinical practice. OBJECTIVES: To determine the effect of the catheter to vein ratio (proportion of the vein measured at the insertion point taken up by the catheter) on rates of symptomatic VTE in patients with a PICC and identify the optimal ratio cut-off point to reduce rates of this adverse event. METHOD: Adult patients waiting for PICC insertion at a large metropolitan teaching hospital were recruited between May and December 2013. Vein diameter at the PICC insertion site was measured using ultrasound with in-built callipers. Participants were followed up at eight weeks to determine if they developed symptomatic VTE. RESULTS: Data were available for 136 patients (50% cancer; 44% infection; 6% other indication for PICC). Mean age was 57 years with 54% males. There were four cases of confirmed symptomatic VTE (two involving the deep veins, one peripheral vein and one pulmonary embolism). Receiver operator characteristic (ROC) analysis determined that a 45% catheter to vein ratio was the ideal cut off point to maximise sensitivity and specificity (AUC 0.761; 95% CI 0.681-0.830). When a ratio of 46% or above was compared to one that was less than or equal to 45% using a log binomial generalised linear model it was found that participants with a catheter to vein ratio >45% were 13 times more likely to suffer VTE (relative risk 13, p=0.022; CI 1.445-122.788). CONCLUSION: It was found that a 45% catheter to vein ratio was the optimal cut off with high sensitivity and specificity to reduce the risk of VTE. However, further research is needed to confirm these results as although adequately powered; the number of cases of VTE was comparatively small, resulting in wide confidence intervals.