Subject(s)
Appendicitis/chemically induced , Gelatin Sponge, Absorbable/adverse effects , Gynecologic Surgical Procedures/adverse effects , Hemostatics/adverse effects , Ovarian Cysts/surgery , Postoperative Hemorrhage/therapy , Appendectomy/methods , Appendicitis/diagnosis , Appendicitis/surgery , Appendix/diagnostic imaging , Appendix/drug effects , Appendix/surgery , Child , Female , Humans , Laparoscopy , Reoperation , UltrasonographyABSTRACT
A 53-year-old man with metastatic melanoma, in remission, presented with an 8-week history of melena and anemia. Initial investigations including upper and lower gastrointestinal endoscopy, capsule endoscopy, and Tc-labeled red blood cell scan did not reveal a source of bleeding. Given the concern over melanoma recurrence, F-FDG PET/CT was performed that demonstrated a focus of intense uptake in the small bowel. Uncomplicated surgical resection of the segment of jejunum containing the lesion was performed, after which the patient reported no further gastrointestinal bleeding. Histopathological assessment of the lesion was consistent with pyogenic granuloma.
Subject(s)
Granuloma, Pyogenic/diagnostic imaging , Jejunum/diagnostic imaging , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Fluorodeoxyglucose F18 , Granuloma, Pyogenic/pathology , Humans , Jejunum/pathology , Male , Middle Aged , RadiopharmaceuticalsSubject(s)
Blood Chemical Analysis , Pathology , Specimen Handling , Toxicokinetics , Toxicology , Cooperative Behavior , WorkforceABSTRACT
Toxicokinetic analysis is an essential part of nonclinical drug development. Advances in bioanalytical techniques have opened up the potential to use smaller sample volumes (microsamples) to assess drug exposure in blood, plasma and/or serum. Microsampling can increase the amount of nonclinical safety information available, improve its validity by linking toxic effects to drug exposure in individual animals and represents the most significant opportunity to reduce animal use in toxicology studies in the short term. In May 2013, a workshop was held with 80 delegates from 33 companies with the aim of sharing information and knowledge on microsampling technologies. This article covers the discussions at the workshop, current practice in the industry, regulatory experiences and the future direction of microsampling across drug development.
Subject(s)
Drug Discovery/legislation & jurisprudence , Drug Evaluation, Preclinical , Drug-Related Side Effects and Adverse Reactions/blood , Models, Animal , Animals , Drug Discovery/methods , Drug Evaluation, Preclinical/methods , Drug-Related Side Effects and Adverse Reactions/diagnosis , HumansABSTRACT
AIMS: Separation of sebaceous adenoma, sebaceoma and well differentiated sebaceous carcinoma is a clinically important distinction which relies on a number of subjective criteria. In routine practice we had noted significant interobserver variability in the classification of these lesions. This study sought to determine the degree of interobserver variability between general surgical pathologists and dermatopathologists in the diagnosis of well differentiated cutaneous sebaceous neoplasms. METHODS: We circulated 61 examples of well circumscribed cutaneous sebaceous neoplasms to nine pathologists, including dermatopathologists and general surgical pathologists who were asked to submit a diagnosis for each case. Fleiss' kappa statistic was used for assessment of interobserver agreement. RESULTS: We found that only seven cases (11%) had consensus agreement across all nine pathologists. Many cases had multiple diagnoses suggested, with three or more submitted diagnoses in 26 cases (43%), while 38 cases (62%) were diagnosed as sebaceous carcinoma by at least one pathologist. There was marked variability amongst the individual pathologists in the proportion of cases diagnosed as carcinoma, ranging from 5% to 57% of cases. Fleiss' kappa statistic for all pathologists across all diagnostic categories was 0.44, amounting to only fair to moderate agreement. CONCLUSIONS: These data indicate that there is substantial interobserver variability in the diagnosis of well circumscribed sebaceous neoplasms. This was seen in both the separation of benign and malignant lesions, as well as in the classification of the benign entities. This interobserver variability is likely to have significant clinical implications in terms of potential for over- or under-treatment, as well as in selection of cases for mismatch repair protein evaluation.
Subject(s)
Adenocarcinoma, Sebaceous/diagnosis , Skin Neoplasms/diagnosis , Adenocarcinoma, Sebaceous/classification , Aged , Aged, 80 and over , Dermatology/standards , Female , Humans , Male , Middle Aged , Observer Variation , Pathology/standards , Skin Neoplasms/classificationABSTRACT
It is common for children and adolescents on growth hormone (GH) treatment to miss one or more injections per week, thereby compromising their linear growth outcome. Among factors likely to affect treatment concordance are patient education and support in the selection of the most appropriate GH injection device. The authors discovered inconsistencies in the process of starting patients on GH therapy throughout the UK, and found that there were no clinical recommendations to support health professionals starting patients on treatment. This article describes the issues involved and the development of practical recommendations for use when starting paediatric patients on long-term GH therapy.
Subject(s)
Growth Disorders/drug therapy , Growth Disorders/nursing , Human Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Patient Education as Topic/standards , Practice Guidelines as Topic/standards , Adolescent , Child , Humans , Patient Compliance , Patient Education as Topic/methods , Pediatric Nursing/standards , Pediatrics/standardsABSTRACT
Toxicity studies in animals are carried out to identify the intrinsic hazard of a substance to support risk assessment for humans. In order to identify opportunities to minimise animal use in regulatory toxicology studies, a review of current study designs was carried out. Pharmaceutical companies and contract research organisations in the UK shared data and experience of standard toxicology studies (ranging from one to nine months duration) in rodents and non-rodents; and carcinogenicity studies in the rat and mouse. The data show that variation in study designs was primarily due to (i) the number of animals used in the main study groups, (ii) the use of animals in toxicokinetic (TK) satellite groups, and (iii) the use of animals in off-treatment recovery groups. The information has been used to propose a series of experimental designs where small adjustments could reduce animal use in practice, while maintaining the scientific objectives.
Subject(s)
Animal Experimentation , Animal Use Alternatives/methods , Toxicity Tests/methods , Animals , Drug Industry , Humans , Research Design , Risk Assessment/methodsABSTRACT
A working party, comprising two animal welfare organisations and some 12 pharmaceutical companies in Europe, was established to minimise the use of the dog in safety testing. As first step, the participants defined the major objectives of preliminary dose-range finding/MTD toxicity studies in non-rodents, defined the principles and requirements for this study type and agreed on a proposal for an optimised study design, based on collective experience of conducting such studies in industry, involving an evaluation of 100 individual study data sets. The suggested study design is explained and described, and reflects current best practice in the pharmaceutical industry in Europe. The implementation of such an optimised design is believed to result in a reduction in the overall numbers of animals used for this purpose, without jeopardising the scientific rationale and usefulness of the studies for informing the conduct of later regulatory studies.
