Numerical solution of an optimal control model of dendritic cell treatment of a growing tumour

A new optimal control model of the interactions between a growing tumour and the host immune system along with an immunotherapy treatment strategy is presented. The model is based on an ordinary differential equation model of interactions between the growing tu- mour and the natural killer, cytotoxic T lymphocyte and dendritic cells of the host immune system, extended through the addition of a control function representing the application of a dendritic cell treat- ment to the system. The numerical solution of this model, obtained from a multi species Runge–Kutta forward-backward sweep scheme, is described. We investigate the effects of varying the maximum al- lowed amount of dendritic cell vaccine administered to the system and find that control of the tumour cell population is best effected via a high initial vaccine level, followed by reduced treatment and finally cessation of treatment. We also found that increasing the strength of the dendritic cell vaccine causes an increase in the number of natural killer cells and lymphocytes, which in turn reduces the growth of the tumour.

A nurse-led model of oncogeriatric assessment

Background There is growing consensus that a multidisciplinary, comprehensive and standardised process for assessing the fitness of older patients for chemotherapy should be undertaken to determine appropriate cancer treatment. Aim This study tested a model of cancer care for the older patient incorporating Comprehensive Geriatric Assessment (CGA), which aimed to ensure that 'fit' individuals amenable to active treatment were accurately identified; 'vulnerable' patients more suitable for modified or supportive regimens were determined; and 'frail 'individuals who would benefit most from palliative regimens were also identified and offered the appropriate level of care. Methods A consecutive-series n=178 sample of patients >65 years was recruited from a major Australian cancer centre. The following instruments were administered by an oncogeriatric nurse prior to treatment: Vulnerable Elders Survey-13; Cumulative Illness Rating Scale (Geriatric); Malnutrition Screening Tool; Mini-mental State Examination; Geriatric Depression Scale; Barthel Index; and Lawton Instrumental Activities of Daily Living Scale. Scores from these instruments were aggregated to predict patient fitness, vulnerability or frailty for chemotherapy. Physicians provided a concurrent (blinded) prediction of patient fitness, vulnerability or frailty based on their clinical assessment. Data were also collected on actual patient outcomes (eg treatment completed as predicted, treatment reduced) during monthly audits of patient trajectories. Data analysis Data analysis is underway. A sample of 178 is adequate to detect, with 90% power, kappa coefficients of agreement between CGA and physician assessments of K>0.90 ("almost perfect agreement"). Primary endpoints comprise a) whether the nurse-led CGA determination of fit, vulnerable or frail agrees with the oncologist's assessments of fit, vulnerable or frail and b) whether the CGA and physician assessments accurately predict actual patient outcomes. Conclusion An oncogeriatric nurse-led model of care is currently being developed from the results. We conclude with a discussion of the pivotal role of nurses in CGA-based models of care.

Cost-effectiveness of a telephone-delivered education programme to prevent early childhood caries in a disadvantaged area : a cohort study

Objectives Early childhood caries is a highly destructive dental disease which is compounded by the need for young children to be treated under general anaesthesia. In Australia, there are long waiting periods for treatment at public hospitals. In this paper, we examined the costs and patient outcomes of a prevention programme for early childhood caries to assess its value for government services. Design Cost-effectiveness analysis using a Markov model. Setting Public dental patients in a low socioeconomic, socially disadvantaged area in the State of Queensland, Australia. Participants Children aged 6 months to 6 years received either a telephone prevention programme or usual care. Primary and secondary outcome measures A mathematical model was used to assess caries incidence and public dental treatment costs for a cohort of children. Healthcare costs, treatment probabilities and caries incidence were modelled from 6 months to 6 years of age based on trial data from mothers and their children who received either a telephone prevention programme or usual care. Sensitivity analyses were used to assess the robustness of the findings to uncertainty in the model estimates. Results By age 6 years, the telephone intervention programme had prevented an estimated 43 carious teeth and saved £69 984 in healthcare costs per 100 children. The results were sensitive to the cost of general anaesthesia (cost-savings range £36 043–£97 298) and the incidence of caries in the prevention group (cost-savings range £59 496–£83 368) and usual care (cost-savings range £46 833–£93 328), but there were cost savings in all scenarios. Conclusions A telephone intervention that aims to prevent early childhood caries is likely to generate considerable and immediate patient benefits and cost savings to the public dental health service in disadvantaged communities.

The effectiveness of health education using the teach-back method on adherence and self-management in chronic disease: A systematic review protocol

Review question/objective What is the effect of using the teach-back method for health education to improve adherence to treatment regimen and self-management in chronic disease? Inclusion criteria Types of participants This review will consider all studies that include adult patients (aged 18 years and over) in any healthcare setting, either as inpatients (eg acute care, medical and surgical wards) or those who attend primary health care, family medical practice, general medical practice, clinics, outpatient departments, rehabilitation or community settings. Participants need to have been diagnosed as having one or more chronic diseases including heart failure, diabetes, cardiovascular disease, cancer, respiratory disease, asthma, chronic obstructive pulmonary disease, chronic kidney disease, arthritis, epilepsy or a mental health condition. Studies that include seriously ill patients, and/or those who have impairments in verbal communication and cognitive function will be excluded. Types of intervention This review will consider studies that investigate the use of the teach-back method alone or in combination with other supporting education, either in routine or research intervention education programs; regardless of how long the programs were and whether or not a follow-up was conducted. The intervention could be delivered by any healthcare professional. The comparator will be any health education for chronic disease that does not include the teach-back method. Types of outcomes Primary outcomes of interest are disease-specific knowledge, adherence, and self-management knowledge, behavior and skills measured using patient report, nursing observation or validated measurement scales. Secondary outcomes include knowledge retention, self-efficacy, hospital readmission, hospitalization, and quality of life, also measured using patient report, nursing observation, hospital records or validated measurement scales.

A cohort study of Chlamydia trachomatis treatment failure in women : a study protocol

Background Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in the developed world and diagnosis rates have increased dramatically over the last decade. Repeat infections of chlamydia are very common and may represent re-infection from an untreated partner or treatment failure. The aim of this cohort study is to estimate the proportion of women infected with chlamydia who experience treatment failure after treatment with 1 gram azithromycin. Methods/design This cohort study will follow women diagnosed with chlamydia for up to 56 days post treatment. Women will provide weekly genital specimens for further assay. The primary outcome is the proportion of women who are classified as having treatment failure 28, 42 or 56 days after recruitment. Comprehensive sexual behavior data collection and the detection of Y chromosome DNA and high discriminatory chlamydial genotyping will be used to differentiate between chlamydia re-infection and treatment failure. Azithromycin levels in high-vaginal specimens will be measured using a validated liquid chromatography – tandem mass spectrometry method to assess whether poor azithromycin absorption could be a cause of treatment failure. Chlamydia culture and minimal inhibitory concentrations will be performed to further characterize the chlamydia infections. Discussion Distinguishing between treatment failure and re-infection is important in order to refine treatment recommendations and focus infection control mechanisms. If a large proportion of repeat chlamydia infections are due to antibiotic treatment failure, then international recommendations on chlamydia treatment may need to be re-evaluated. If most are re-infections, then strategies to expedite partner treatment are necessary.

End-of-life care pathways for improving outcomes in caring for the dying (Review)

Background This is an updated version of a Cochrane review first published in Issue 1, 2010 of The Cochrane Library. In many clinical areas, integrated care pathways are utilised as structured multidisciplinary care plans that detail essential steps in caring for patients with specific clinical problems. In particular, care pathways for the dying have been developed as a model to improve care of patients who are in the last days of life. The care pathways were designed with an aim of ensuring that the most appropriate management occurs at the most appropriate time and that it is provided by the most appropriate health professional. There have been sustained concerns about the safety of implementing end-of-life care pathways, particularly in the UK. Therefore, there is a significant need for clinicians and policy makers to be informed about the effects of end-of-life care pathways with a systematic review. Objectives To assess the effects of end-of-life care pathways, compared with usual care (no pathway) or with care guided by another end-of-life care pathway across all healthcare settings (e.g. hospitals, residential aged care facilities, community). In particular, we aimed to assess the effects on symptom severity and quality of life of people who are dying; those related to the care such as families, carers and health professionals; or a combination of these. Search Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2013), MEDLINE, EMBASE, PsycINFO, CINAHL, review articles and reference lists of relevant articles.We conducted the original search in September 2009, and the updated search in June 2013. Selection Criteria All randomised controlled trials (RCTs), quasi-randomised trial or high-quality controlled before-and-after studies comparing use versus non-use of an end-of-life care pathway in caring for the dying. Data Collection and Analysis Two review authors assessed the results of the searches against the predetermined criteria for inclusion. Main Results The original review identified 920 titles. The updated search found 2042 potentially relevant titles (including the original 920), but no additional studies met criteria for inclusion in the review update. Authors’ Conclusions With sustained concerns about the safety of the pathway implementation and the lack of available evidence on important patient and relative outcomes, recommendations for the use of end-of-life pathways in caring for the dying cannot be made. Since the last version of this review, no new studies met criteria for inclusion in the review update. With recently documented concerns related to the potential adverse effects associated with Liverpool Care Pathway (the most commonly used end-of-life care pathway), we do not recommend decision making based on indirect or low-quality evidence. All health services using end-of-life care pathways are encouraged to have their use of the pathway, to date, independently audited. Any subsequent use should be based on carefully documented evaluations. Large RCTs or other well-designed controlled studies are urgently required for the evaluation of the use of end-of-life care pathways in caring for dying people in various clinical settings. In future studies, outcome measures should include benefits or harms concerning the outcomes of interest in this review in relation to patients, families, carers and health professionals.

Surgical resection for non-small cell lung cancer : clinical features and outcomes for a consecutive series at an Irish tertiary referral centre

Background: Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors. Methods: Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed. The clinical features and outcomes of all patients with non-small cell lung cancer (NSCLC) stage I-IV were recorded. Results: A total of 654 patients underwent surgical resection with curative intent during the study period. Median overall survival for the entire cohort was 37 months. The median age at operation was 66 years, with males accounting for 62.7 %. Squamous cell type was the most common histological subtype, and lobectomies were performed in 76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics associated with improved survival by univariate analysis include younger age, female sex, smaller tumour size, smoking status, lobectomy, lower T and N status and less advanced pathological stage. Age, gender, smoking status and tumour size, as well as T and N descriptors have emerged as independent prognostic factors by multivariate analysis. Conclusion: We identified several factors that predicted outcome for NSCLC patients undergoing curative-intent surgical resection. Survival rates in our series are comparable to those reported from other thoracic surgery centres. © 2012 Royal Academy of Medicine in Ireland.

Clinical skin examination outcomes after a video-based behavioral intervention analysis from a randomized clinical trial

Importance Older men are at risk of dying of melanoma. Objective To assess attendance at and clinical outcomes of clinical skin examinations (CSEs) in older men exposed to a video-based behavioral intervention. Design, Setting, and Participants This was a behavioral randomized clinical trial of a video-based intervention in men aged at least 50 years. Between June 1 and August 31, 2008, men were recruited, completed baseline telephone interviews, and were than randomized to receive either a video-based intervention (n = 469) or brochures only (n = 461; overall response rate, 37.1%) and were again interviewed 7 months later (n = 870; 93.5% retention). Interventions Video on skin self-examination and skin awareness and written informational materials. The control group received written materials only. Main Outcomes and Measures Participants who reported a CSE were asked for the type of CSE (skin spot, partial body, or whole body), who initiated it, whether the physician noted any suspicious lesions, and, if so, how lesions were managed. Physicians completed a case report form that included the type of CSE, who initiated it, the number of suspicious lesions detected, how lesions were managed (excision, nonsurgical treatment, monitoring, or referral), and pathology reports after lesion excision or biopsy. Results Overall, 540 of 870 men (62.1%) self-reported a CSE since receiving intervention materials, and 321 of 540 (59.4%) consented for their physician to provide medical information (received for 266 of 321 [82.9%]). Attendance of any CSE was similar between groups (intervention group, 246 of 436 [56.4%]; control group, 229 of 434 [52.8%]), but men in the intervention group were more likely to self-report a whole-body CSE (154 of 436 [35.3%] vs 118 of 434 [27.2%] for control group; P = .01). Two melanomas, 29 squamous cell carcinomas, and 38 basal cell carcinomas were diagnosed, with a higher proportion of malignant lesions in the intervention group (60.0% vs 40.0% for controls; P = .03). Baseline attitudes, behaviors, and skin cancer history were associated with higher odds of CSE and skin cancer diagnosis. Conclusions and Relevance A video-based intervention may increase whole-body CSE and skin cancer diagnosis in older men. Trial Registration: anzctr.org.au Identifier: ACTRN12608000384358

A pilot study on understanding the journey of advanced prostate cancer patients

Objective: To understand the journey of advanced prostate cancer patients for supporting development of an innovative patient journey browser. Background: Prostate cancer is one of the common cancers in Australia. Due to the chronic nature of the disease, it is important to have effective disease management strategy and care model. Multi-disciplinary care is a well-proven approach for chronic disease management. The Multi-disciplinary team (MDT) can function more effectively if all the required information is available for the clinical decision support. The development of innovative technology relies on an accurate understanding of the advanced prostate cancer patient’s journey over a prolonged period. This need arises from the fact that advanced prostate cancer patients may follow various treatment paths and change their care providers. As a result of this, it is difficult to understand the actual sources of patient’s clinical records and their treatment patterns. The aim of the research is to understand variable sources of clinical records, treatment patterns, alternative therapies, over the counter (OTC) medications of advanced prostate cancer patients. This study provides better and holistic understanding of advanced prostate cancer journey. Methods: The study was conducted through an on-line survey developed to seek and analyse the responses from the participants. The on-line questionnaire was carefully developed through consultations with the clinical researchers at the Australian Prostate Cancer Research Centre-Queensland, prostate cancer support group representatives and health informaticians at the Australian e-Health Research Centre. The non-identifying questionnaire was distributed to the patients through prostate cancer support groups in Queensland, Australia. The pilot study was carried out between August 2010 and December 2010. Results: The research made important observations about the advanced prostate cancer journey. It showed that General Practitioner (GP) was the common source of patient’s clinical records (41%) followed by Urologist (14%) and other clinicians (14%). The data analysis also showed that selenium was the common complementary supplement (55%) used by the patients and about 48% patients did not use any OTC drugs. The most common OTC used by the patients was Paracetamol (about 45%). Conclusion: The results have provided a foundation to the architecture of the proposed technology solution. The outcomes of this study are incorporated in design of the proposed patient journey browser system. A basic version of the system is currently being used at the advanced prostate cancer MDT meetings.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

A prospective model of care for breast cancer rehabilitation : bone health and arthralgias

Musculoskeletal health can be compromised by breast cancer treatment. In particular, bone loss and arthralgias are prevalent side effects experienced by women treated with chemotherapy and/or adjuvant endocrine therapy. Bone loss leads to osteoporosis and related fractures, while arthralgias threaten quality of life and compliance to treatment. Because the processes that lead to these musculoskeletal problems are initiated when treatment begins, early identification of women who may be at higher risk of developing problems, routine monitoring of bone density and pain at certain stages of treatment, and prudent application of therapeutic interventions are key to preventing and/or minimizing musculoskeletal sequelae. Exercise may be a particularly suitable intervention strategy because of its potential to address a number of impairments; it may slow bone loss, appears to reduce joint pain in noncancer conditions, and improves other breast cancer outcomes. Research efforts continue in the areas of etiology, measurement, and treatment of bone loss and arthralgias. The purpose of this review is to provide an overview of the current knowledge on the management and treatment of bone loss and arthralgias in breast cancer survivors and to present a framework for rehabilitation care to preserve musculoskeletal health in women treated for breast cancer.

Promoting posttraumatic growth in police recruits : preliminary results of a randomised controlled resilience intervention trial

Recent research has demonstrated that the same experiences that may elicit symptoms of post-traumatic stress disorder (PTSD) in emergency service personnel can also provide a catalyst for positive personal changes such as posttraumatic growth (PTG). In this research newly recruited police officers (N = 412) participated in a randomised control trial of a program specifically designed to promote mental health. On entry to the academy, new recruits were randomly allocated, by classrooms, to either a treatment as usual condition (i.e., existing psychoeducation program) or to the intervention group. The Promoting Resilient Officers (PRO) program is a resilience building intervention adapted from an earlier resilience building program in collaboration with the police service. The PRO program also includes additional components on trauma and PTG. The current research included the participants who had experienced trauma prior to or during the research period (N = 246). It was hypothesised that participation in the PRO program would increase levels of PTG and lower levels of PTSD when compared to recruits in the control condition. Using multilevel modelling and post-hoc analyses, results indicated there were significantly higher levels of PTG across multiple dimensions when compared to the control group. There was no effect on PTSD symptoms with both conditions showing a floor effect. The research indicated the potential value of developing interventions that elicit reflections on the potential for positive as well as negative outcomes of experiencing traumatic and other highly challenging events.

Targeted disruption of the JAK2/STAT3 pathway in combination with systemic administration of paclitaxel inhibits the priming of ovarian cancer stem cells leading to a reduced tumor burden

Chemotherapy resistance associated with recurrent disease is the major cause of poor survival of ovarian cancer patients. We have recently demonstrated activation of the JAK2/STAT3 pathway and the enhancement of a cancer stem cell (CSC)-like phenotype in ovarian cancer cells treated in vitro with chemotherapeutic agents. To elucidate further these mechanisms in vivo,we used a two-tiered paclitaxel treatment approach in nude mice inoculated with ovarian cancer cells. In the first approach, we demonstrate that a single intraperitoneal administration of paclitaxel in mice 7 days after subcutaneous transplantation of the HEY ovarian cancer cell line resulted in a significant increase in the expression of CA125, Oct4, and CD117 in mice xenografts compared to control mice xenografts which did not receive paclitaxel. In the second approach, mice were administered once weekly with paclitaxel and/or a daily dose of the JAK2-specific inhibitor, CYT387, over 4weeks. Mice receiving paclitaxel only demonstrated a significant decrease in tumor volume compared to control mice. At the molecular level, mouse tumors remaining after paclitaxel administration showed a significant increase in the expression of Oct4 and CD117 coinciding with a significant activation of the JAK2/STAT3 pathway compared to control tumors. The addition of CYT387 with paclitaxel resulted in the suppression of JAK2/STAT3 activation and abrogation of Oct4 and CD117 expression in mouse xenografts. This coincided with significantly smaller tumors in mice administered CYT387 in addition to paclitaxel, compared to the control group and the group of mice receiving paclitaxel only. These data suggest that the systemic administration of paclitaxel enhances Oct4- and CD117-associated CSC-like marker expression in surviving cancer cells in vivo, which can be suppressed by the addition of the JAK2-specific inhibitor CYT387, leading to a significantly smaller tumor burden. These novel findings have the potential for the development of CSC-targeted therapy to improve the treatment outcomes of ovarian cancer patients.

Health education and the control of intestinal worm infections in China : a new vision

Background: The transmission of soil-transmitted helminths (STHs) is associated with poverty, poor hygiene behaviour, lack of clean water and inadequate waste disposal and sanitation. Periodic administration of benzimidazole drugs is the mainstay for global STH control but it does not prevent re-infection, and is unlikely to interrupt transmission as a stand-alone intervention. Findings: We reported recently on the development and successful testing in Hunan province, PR China, of a health education package to prevent STH infections in Han Chinese primary school students. We have recently commenced a new trial of the package in the ethnically diverse Xishuangbanna autonomous prefecture in Yunnan province and the approach is also being tested in West Africa, with further expansion into the Philippines in 2015. Conclusions: The work in China illustrates well the direct impact that health education can have in improving knowledge and awareness, and in changing hygiene behaviour. Further, it can provide insight into the public health outcomes of a multi-component integrated control program, where health education prevents re-infection and periodic drug treatment reduces prevalence and morbidity.

In-hospital mortality rates after a cemented femoral component for displaced neck of femur fractures

Aim This prospective cohort study investigated whether the use of preoperative anticoagulants is an independent risk factor for the outcomes of surgical treatment of patients with a neck of femur fracture. Methods Data was obtained from a prospectively collected database. All patients admitted for a neck of femur fracture between Nov 2010 and Oct 2011 were included. This resulted in three hundred twenty-eight patients with 330 neck of femur fractures. Four groups were defined; patients preoperatively (i) on aspirin (n = 105); (ii) on clopidogrel (n = 28); (iii) on warfarin (n = 30), and; (iv) without any anticoagulation history (n = 167, the control group). The non-warfarin group included the aspirin group, clopidogrel group and the control group. Primary outcome was the in-hospital mortality. Secondary outcomes were the postoperative complications, return to theatre and length of stay. Results Thirteen in-hospital deaths were identified, 4 deaths in the aspirin group, 1 death in the clopidogrel group, 2 deaths in the warfarin group and 6 deaths in the control group. No significant difference in the mortality rates was found between the different groups. Also in the secondary outcomes, no significant difference was found between the four groups. A trend to a higher wound complication rate for the warfarin group was detected. Conclusion The use of clopidrogel or aspirin pre operatively is not an influence on short term patient outcome for patients with a neck of femur fracture. Surgical procedures should not be delayed to reverse their influence.