Off-label drug use in oncology: a systematic review of literature.

WHAT IS KNOWN AND OBJECTIVE: The off-label use of medicines is widespread in several diseases. This type of prescribing practice is particularly more acute in oncology. However, the suitability of anticancer medications for off-label use remains an issue of controversy, due to uncertainty around the clinical benefits and potential toxicities, limited evidence to support clinical decision-making, increased out-of-pocket costs for patients and ethical concerns around the lack of informed consent. Currently, data pertaining to the global prevalence of off-label use in cancer therapy are lacking. The aim of this review was to provide an overview of off-label drug use prevalence in oncology. METHODS: A systematic literature search was performed in PubMed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from 1975 to 2016. Studies assessing the prevalence of off-label use of anticancer drugs were included. DATA SYNTHESIS: Of the 199 eligible papers retrieved, 23 studies were included in this systematic literature review. Off-label drug use in inpatients ranged from 18% to 41%. Among adult patients with cancer, 13%-71% received a minimum of one off-label chemotherapy. The main reasons for off-label drug use were 'drug unapproved for specific tumour' and 'modified drug applications'. Among adults, metastatic cancers and palliative care patients received the most off-label drugs. The off-label drug use unsupported by standard treatment guidelines or drug compendia was in the range of 7%-31%. CONCLUSION: Off-label drug use in cancer therapy is commonly practised but outcomes could vary significantly. Hence, greater scrutiny and robust clinical guidance is needed to establish the favourable benefit-risk ratio for patients at the time of prescribing at each level of oncology care to facilitate rational off-label prescribing.

Studies on monitoring and tracking genetic resources: an executive summary.

The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information.

Late-life depression: current issues and new challenges.

INTRODUCTION: Depression is a common psychiatric disorder in older people but tends to be underrecognised and undertreated, leading to impaired functioning, increased morbidity and mortality including suicide, and greater service utilisation. METHODS: A Medline search of journal articles on depression in older people, which highlighted specific and pertinent issues of prevalence, classification, screening instruments, elderly suicide and various treatment modalities, was done. RESULTS: Late-life depression represents a heterogenous group of mood disturbances that may present with atypical features and occur in a complex medical psychosocial context. Appropriate screening and assessment procedures and holistic, multidisciplinary treatment approaches are discussed. Future challenges lie in areas of early detection and intervention, advances in treatment strategies, training and service developments and effective prevention programmes. CONCLUSION: By raising awareness and understanding of depression among primary healthcare and other healthcare practitioners, more depressed elderly with comorbid medical problems can be successfully identified and helped.

Validation and comparison of three brief depression scales in an elderly Chinese population.

The study aimed to establish the diagnostic accuracy of the Geriatric Depression Scale (GDS), the Even Briefer Assessment Scale for Depression (EBAS DEP), and the single question test for depression in our elderly Chinese population, and to determine if any one instrument was to be preferred. Ninety-eight community-living, socially active and non-depressed elderly and 75 patients diagnosed with depression were administered the three depression scales. Receiver operating characteristics (ROC) were employed to determine the optimal cut-off scores for the GDS and EBAS DEP, and the diagnostic performance of all three instruments were then compared. ROC analysis indicated an optimal cut-off score of 4 and above for the 15-item GDS, with a sensitivity of 84.0% and a specificity of 85.7%, while the EBAS DEP had 77.3% sensitivity and 89.8% specificity at the optimal cut-off score of 3 and above. The sensitivity and specificity of the single question were 64.0% and 94.9%, respectively. The non-parametric test of the areas-under-the-curve showed no significant difference between the diagnostic performances of the GDS and the EBAS DEP; visually, however, the ROC plot of the GDS was superior. The GDS, the EBAS DEP, and the single question were all valid screening tools for depression in the elderly Chinese population. For busy physicians, there is rationale to first use the single-question test, supplemented where necessary with either the GDS or the EBAS DEP, as an efficient diagnostic strategy for identifying depression amongst older Chinese patients.

An alternative approach to the management dilemma of the mildly dyskaryotic smear based on audit of outcome.

We describe a study which takes an alternative approach to the management dilemma of the mildly dyskaryotic cervical smear. Two hundred and fifty women with a smear showing mild dyskaryosis were studied by auditing the clinical outcome as well as the cost. The cost of providing the colposcopy services during the index year was approximately pounds sterling 70000 for an average size district general Hospital. The proportion of women managed by the current guidelines and avoiding colposcopy after a first mildly dyskaryotic smear was only 30%. The majority of patients will eventually have colposcopy despite a policy of cytological surveillance. The alternative approach, to offer colposcopy immediately after the first mildly dyskaryotic smear, would result in a small increase in cost for our unit, equivalent to one extra colposcopy patient per week.

A comparison of endoscopic and capsule small intestinal biopsy techniques in children with upper gastrointestinal disorders.

OBJECTIVE: To compare the adequacy for histological diagnosis and morphometric analysis of small intestinal biopsies obtained by either endoscopic forceps or a capsule technique. METHODOLOGY: Small intestinal biopsies from 176 children were reviewed, 92 obtained by endoscopy and 84 by capsule. RESULTS: The adequacy for making a histological diagnosis was 96 and 81% for endoscopic and capsule biopsies, respectively, and for morphometric analysis it was 86 and 71%. There were more tissue specimens from children who had endoscopic compared with capsule biopsies (2.3 vs 1.8 specimens per patient). CONCLUSIONS: Endoscopic biopsies provide better specimens for histological diagnosis and endoscopy has the advantage of allowing macroscopic assessment of the upper gastrointestinal tract which can be of value in recognizing unexpected pathology and in identifying patchy mucosal changes.

Thrombosed jugular vein presenting as a hard neck mass.

We report an unusual case of thrombosis of a dilated external jugular vein presenting as a hard neck mass of sudden onset. The lesion's presentation, investigation, treatment and pathology are discussed.

Colonic stricture in a boy with cystic fibrosis.

Many problems may arise within the gastrointestinal tract of patients with cystic fibrosis. We report a new cause of subacute intestinal obstruction due to a fibrotic stricture of the ascending colon in a child with cystic fibrosis. Treatment was with a right hemicolectomy. There has been no recurrence after nine months follow-up. Recent similar cases suggest that this new pathology is linked to the use of enteric-coated high-strength pancreatin microspheres.

A pilot study into the prevalence of ophthalmic disease in the Indian population of Southall.

A pilot study was carried out to determine the prevalence of ophthalmic disease in the Indian community of Southall and to ascertain the best methods applicable for a larger formal study. Three sites were chosen for the study, a Sikh gurdwara, a mosque and a Hindu temple. The subjects were volunteers aged 30 years and over who had visited the appropriate place of worship at least twice in the previous month. A total of 184 subjects were examined. The prevalence of blindness was 2.7% by the World Health Organization (WHO) criteria, while 9.8% had uniocular blindness. The prevalence of glaucoma and ocular hypertension was 2.7% and 7%, respectively. Of the 184 subjects examined, 58% had cataract and 3.8% had age-related maculopathy. The prevalence of visually disabling trachomatous eye disease was 9.7%. The prevalence of diabetes mellitus was 17.9%, and that of hypertension 22.8%. This small study suggests that people with origins from the Indian subcontinent have a higher prevalence of ophthalmic disease than the Caucasian population.

Sample mass determination using Compton- and total scattered excitation radiation for energy-dispersive x-ray fluorescent analysis of trace elements in soft tissue specimens.

Compton profiles and total scattered intensities have been measured to determine the total sample mass, analyzed by an x-ray probe energy-dispersive analyzer. Under photon excitation, fluorescent x rays are emitted from the trace elements in a biological matrix. From incident radiation, the number of photons which are Commpton and elastically scattered by low-atomic-number elements is directly proportional to the total specimen mass. Tissue specimen masses have been measured from Compton intensities using Zr Kalpha and Ma Kalpha excitation x rays and mass calibration standards based upon carbon scattering. This procedure has been extended to include lower-energy excitation radiation, such as Cu, where the resolution of an energy-dispersion system requires that the total scattered intensity be used to determine the sample mass. Trace element weight-fraction concentrations are determined from this scheme with precisions of 1% in 2%, relying only upon information contained in the energy-dispersive x-ray spectrum. By adjusting for the difference between tissue and corbon scattering the accuracy of the elemental weight-fraction concentrations is brought to within 10% of elemental concentrations measured by atomic absorption spectroscopy, for samples weighing up to 25 mg. In the case of heavier samples, absorption corrections are necessary to achieve this accuracy.

Line-focusing x-ray monochromator for the analysis of trace elements in biological specimens.

A line-focusing x-ray monochromator has been designed and developed to be used with an energy dispersive detection system for the quantitative analysis of trace elements in biological specimens. This instrument uses a cylindrically curved Johansson-type crystal to monochromatize and focus the excitation radiation into a line 0.5 mm wide and 40 mm long. The excitation radiation chosen for these experiments was Mo Kalpha and the total intensity of the line-focused beam was estimated to be 2 X 10(7) cps. Because of the narrow width and high power density of the excitation between beam, small tissue specimens 1 X 1 X 12 mm in size along with a single strand of hair were analyzed for trace elements from Al through Sr. For the transition elements, concentrations of a few parts per million were easily detected with this analyzer.

Production, purification and characterization of thermomycolase, the extracellular serine protease of the thermophilic fungus Malbranchea pulchella var. sulfurea.

The thermophilic fungus Malbranchea pulchella produces a single extracellular, alkaline, serine protease when grown at 45 degrees C, on 2% casein as sole carbon source. The growth-associated production of protease in submerged cultures was inhibited by addition of glucose, amino acids, or yeast extract. A simple four-step purification which yields homogeneous protease in 78% yield is described. The protease has an isoelectric point of 6.0, a pH optimum of 8.5, and is completely inhibited by serine protease inhibitors. A specificity study with small synthetic ester substrates indicated that the protease preferentially hydrolyzed bonds situated on the carboxyl side of aromatic or apolar amino acid residues which are not beta-branched, positively charged or of the D configuration. Peptidase substrates and others such as N-acetyl-L-tyrosine-ethyl ester were not hydrolyzed. The protease was stable over a broad range of pH (6.5-9.5 at 30 degrees C, 20 h), and was particularly thermostable (t1/2 = 110 min at 73 degrees C, pH 7.4) in the presence of Ca2+ (10 mM). Macromolecules and Ca2+ also provide protection against the significant autolysis which occurs at pure protease concentrations greater than 0.01 mg/mo, as well as against surface denaturation which is enhanced by the presence of a silicone antifoam agent. Hence the stability of protease in submerged cultures is rationalized.

A syndrome manifested by brittle hair with morphologic and biochemical abnormalities, developmental delay and normal stature.

We have presented 2 affected sibs-a male and female-with unaffected parents and sib from a small remote northern Mexican village. The syndrome includes mental deficit, brittle hair with decreased cuticular layer and an apparently collapsed cortex. The patients' hair contains decreased sulfur content and increased concentrations of trace elements as determined by x-ray fluorescent spectroscopy. Studies are underway to evaluate other apparently similarly affected children from the village where our family originated.