Development of an integrated electronic platform for patient self-report and management of adverse events during cancer treatment.

BACKGROUND: Significant adverse events (AE) during cancer therapy disrupt treatment and escalate to emergency admissions. Approaches to improve the timeliness and accuracy of AE reporting may improve safety and reduce health service costs. Reporting AE via patient reported outcomes (PROs), can improve clinician-patient communication and making data available to clinicians in 'real-time' using electronic PROs (ePROs) could potentially transform clinical practice by providing easily accessible records to guide treatment decisions. This manuscript describes the development of eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is a National Institute for Health Research-funded programme, a system for patients to self-report and manage AE online during and after cancer treatment. MATERIALS AND METHODS: A multidisciplinary team of IT experts, staff and patients developed using agile principles a secure web application interface (QStore) between an existing online questionnaire builder (QTool) displaying real-time ePRO data to clinicians in the electronic patient record at Leeds Teaching Hospitals NHS Trust. Hierarchical algorithms were developed corresponding to Common Terminology Criteria for Adverse Events grading using the QTool question dependency function. Patient advocates (N = 9), patients (N = 13), and staff (N = 19) usability tested the system reporting combinations of AE. RESULTS: The eRAPID system allows patients to report AE from home on PC, tablet or any web enabled device securely during treatment. The system generates immediate self-management advice for low or moderate AE and for severe AE advice to contact the hospital immediately. Clinicians can view patient AE data in the electronic patient record and receive email notifications when patients report severe AE. CONCLUSIONS: Evaluation of the system in a randomised controlled trial in breast, gynaecological and colorectal cancer patients undergoing systemic therapy is currently underway. To adapt eRAPID for different treatment groups, pilot studies are being undertaken with patients receiving pelvic radiotherapy and upper gastrointestinal surgery. ISRCTN88520246.

Beyond lip service and box ticking: how effective patient engagement is integral to the development and delivery of patient-reported outcomes.

BACKGROUND: In the UK, demonstration of patient and public involvement (PPI) is now a funding requirement. Despite advice being available to researchers regarding PPI, levels of engagement are variable. Patient involvement has been at the core of the Leeds Psychosocial Oncology and Clinical Practice Research Group since 2007 when a local Research Advisory Group (RAG) was established. In addition, we work with experienced patient advocates from national groups. METHODS: The RAG is led by designated researchers who manage and communicate with members. The RAG is invited to twice yearly meetings with the full research team when study findings are disseminated and advice sought. The meetings are also an opportunity to socialise and thank members. Effective partnerships and engagement require good communication, building relationships over time and tailoring involvement to individuals' skills and experience. RESULTS: Patients have been involved in design, planning new projects and assisting with grant proposals; development, pilot testing of interview strategies and question generation, project steering groups and management teams, development of self-management advice for online patient portals; implementation, extensive beta testing of new questionnaire builder software to enable collection of online patient-reported outcomes (PRO) and study websites, cognitive interviews to develop PRO items; dissemination, co-authorship of papers and presentations, attendance/representation of the group at conferences. CONCLUSION: The involvement of patient advocates is integral to ensuring PRO development remains patient-centred. Having a co-operative, well-established local PPI group and nationally active patient collaborators has had a rewarding and significant impact on our research programmes.

[3T-AI: a new treatment algorithm for anal incontinence with a higher evidence level]. / 3T-AI: Ein neuer, mit höherer Evidenz versehener Behandlungsalgorithmus bei analer Inkontinenz.

BACKGROUND: The evidence for conservative treatment of anal incontinence is poor. In our first publication [Schwandner et al. Dis Colon Rectum 2010; 53: 1007-1016] we demonstrated that a novel therapeutic concept, termed triple target treatment (3T), combining amplitude-modulated medium frequency stimulation and electromyography biofeedback (EMG-BF) was superior to EMG-BF alone. Questions about the required treatment duration and the relevant subgroups of patients with sphincter damage and damaged anal sensibility were not addressed. METHODS: We enrolled 158 patients with anal incontinence in this randomized study. Here, we -report on the important subgroup analyses of patients with and without sphincter damage and damaged anal sensibility for the endpoints Cleveland Clinic Score (CCS) and success record. Using the results of this study we propose a novel treatment algorithm which is open for discussion. RESULTS: In patients with sphincter damage, the median difference on the CCS from baseline to 9 months was 5 points higher for 3T than for EMG-BF (95 % confidence interval 0-8; p = 0.0168). While 47 % of the patients with sphincter damage became continent with 3T, only 18 % did with EMG-BF (p = 0.0036). Ten of 17 patients in the 3T group regained anal sensibility after 3 months stimulation. There was tendency towards improved continence in patients with neuropathy upon 3T treatment (p = 0.1219). CONCLUSIONS: 3T is superior to EMG-BF alone for patients with sphincter damage and neuropathic anal incontinence. It is a successful key element within our treatment algorithm, even in patients with sphincter damage and neuropathic anal incontinence.

Behavioural satiety sequence (BSS): separating wheat from chaff in the behavioural pharmacology of appetite.

The history of anti-obesity drug development is far from glorious, with transient magic bullets and only a handful of agents currently licensed for clinical use. In view of recent progress in our understanding of the multiplicity of signalling pathways involved in appetite regulation, and the resultant deluge of reports on the anorectic efficacy of novel therapies, it seems timely to stress the need to differentiate treatments that suppress intake by primary means from those that only indirectly achieve this endpoint. The current article reviews the conceptual history of the behavioural satiety sequence (BSS), also known as the behavioural sequence of satiety, post-ingestive satiety, and the postprandial satiety sequence. Early research confirmed that natural satiation, produced by a caloric load on the gut, is associated with a predictable transition from feeding through grooming to resting. Although many less naturalistic manipulations are also capable of reducing food intake, very few do so without disrupting the normal structure of this feeding cycle. Thus, while CCK and d-fenfluramine reduce intake by accelerating but otherwise maintaining the integrity of the BSS, other anorectic interventions disrupt the BSS through response competition (e.g. d-amphetamine), nausea/discomfort (e.g. lithium chloride) and/or interference with taste-mediated positive feedback (e.g. quinine adulteration of the diet). A substantial literature now strongly supports the specific involvement of serotonin 5-HT(1B) and 5-HT(2C) receptor subtypes in satiety and in the anorectic effect of agents such as fenfluramine and fluoxetine. Recent BSS analyses have also identified rather selective anorectic profiles for the dual noradrenaline and 5-HT reuptake inhibitor sibutramine, the orexin-1 receptor antagonist SB-334867, and the broad spectrum opioid receptor antagonist naloxone. However, similar analyses have offered little/no support for the anorectic potential of the gut peptide PYY(3-36) while the acute anorectic efficacy of cannabinoid CB1 receptor antagonist/inverse agonists appears largely to be secondary to response competition. In contrast, studies with low-dose combinations of naloxone and CB1 receptor antagonist/inverse agonists have very recently confirmed the potential of drug polytherapies not only in appetite suppression but also in attenuating/eliminating unwanted side-effects. In sum, as BSS analysis offers a reliable means of differentiating the wheat (primary anorectics) from the chaff (secondary anorectics), it should form an integral part of early phase testing in any anti-obesity drug screening programme.

PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

[Parathyroid gland carcinoma with postoperative encephalopathy]. / Nebenschilddrüsencarcinom in Zusammenhang mit einem postoperativen Durchgangssyndrom.

We present a 78-year-old patient who suffered from symptomatic transitory psychotic syndrome after laparotomy. Persisting somnolence appeared with cardiopulmonary decompensation and gastrointestinal atony. Due to prolonged hypercalcemia primary hyperparathyreoidism was diagnosed. Resection of a large carcinoma of the parathyroids led to continuous clinical improvement.

Volume, staging and grading of gastro-intestinal carcinoma--a population-based study.

All cases of the Regional Cancer Registry, North Baden who developed a gastro-intestinal cancer during the period 1975-1980 were re-examined according to the following parameters: tumor volume, pT stage, pN stage, grading. In the period considered, 8424 cases out of 14,061 cases with histologically proven gastrointestinal cancer could be grouped according to the pT stage. Most of the cases were operated at the pT2 or pT3 stage. Remarkable differences in the different tumor localizations were obtained. Stomach carcinoma had the highest percentage of the pT4 stage (36.2%), rectum carcinoma the lowest (7%). In all primaries a close coherence of tumor volume and pT stage was noted. Carcinoma at the pT1 stage measured 20 cm3 on average, those at the pT4 stage 170 cm3. No coherence of staging and age of the patients could be obtained. Younger patients showed a higher percentage of undifferentiated carcinoma than older patients. Survival data could not be obtained due to the data protection law.

[Population based data in North Baden on malignant tumors of the gastrointestinal tract]. / Bevölkerungsbezogene Daten in Nordbaden über bösartige Geschwülste des Magen-Darm-Traktes.

Population-based data of malignomas of the gastro-intestinal tract were evaluated from the regional cancer registry North-Baden for the period of 1971-1980. The age standardized incidence of oesophagus carcinomas shows a steady level of 4.5/100,000 (males) and 0.5/100,000 (females); the age standardized incidence of stomach carcinomas increased from 1971 to 1974, then shows a decline for both males and females, where the colon carcinomas show an increase of 80% for the same time period, also the cancer of the small intestines and of the rectum, increased slightly. Compared to data of other cancer registries the world standardized incidence of rectum carcinomas is of the same level as the data from the cancer registry of Bas-Rhin and is with an incidence of 25.8/100,000 males; 16.2/100,000 females above the incidence of all other cancer registries. The post-operative TNM-stage differs for the different primary topographies. Especially patients with colon carcinomas were operated when the carcinoma was in an advanced stage, patients with rectum carcinomas were operated at a less advanced stage. Male patients with an oesophagus carcinoma showed in a significant percentage an advanced smoking and alcohol consumption, compared to patients suffering from stomach, colon or rectum carcinomas. The specialized organisation of the cancer registry shows a high efficiency due to the requirements of the public health system, and is very useful in the evaluation of descriptive and analytic population-based cancer data.