[Cannabinoids in palliative care: Systematic review and meta-analysis of efficacy, tolerability and safety]. / Cannabinoide in der palliativen Versorgung : Systematische Übersicht und Metaanalyse der Wirksamkeit, Verträglichkeit und Sicherheit.

BACKGROUND: Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted. MATERIALS AND METHODS: An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of ≥ 2 weeks and ≥ 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated. RESULTS: Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 × 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD: 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD: - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD: 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD: 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD: 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD: 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD: 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer-associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found. CONCLUSION: Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long-term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point.

Outbreak of influenza in highly vaccinated crew of U.S. Navy ship.

An outbreak of influenza A (H3N2) occurred aboard a U.S. Navy ship in February 1996, despite 95% of the crew's having been appropriately vaccinated. Virus isolated from ill crew members was antigenically distinct from the vaccination strain. With an attack rate of 42%, this outbreak demonstrates the potential for rapid spread of influenza in a confined population and the impact subsequent illness may have upon the workplace.

The TRANSFAC system on gene expression regulation.

The TRANSFAC database on transcription factors and their DNA-binding sites and profiles (http://www.gene-regulation.de/) has been quantitatively extended and supplemented by a number of modules. These modules give information about pathologically relevant mutations in regulatory regions and transcription factor genes (PathoDB), scaffold/matrix attached regions (S/MARt DB), signal transduction (TRANSPATH) and gene expression sources (CYTOMER). Altogether, these distinct database modules constitute the TRANSFAC system. They are accompanied by a number of program routines for identifying potential transcription factor binding sites or for localizing individual components in the regulatory network of a cell.

TRANSFAC: an integrated system for gene expression regulation.

TRANSFAC is a database on transcription factors, their genomic binding sites and DNA-binding profiles (http://transfac.gbf.de/TRANSFAC/). Its content has been enhanced, in particular by information about training sequences used for the construction of nucleotide matrices as well as by data on plant sites and factors. Moreover, TRANSFAC has been extended by two new modules: PathoDB provides data on pathologically relevant mutations in regulatory regions and transcription factor genes, whereas S/MARt DB compiles features of scaffold/matrix attached regions (S/MARs) and the proteins binding to them. Additionally, the databases TRANSPATH, about signal transduction, and CYTOMER, about organs and cell types, have been extended and are increasingly integrated with the TRANSFAC data sources.

Metabolic drug pointing and information processing.

Computer supported drug design is based on the biochemical information for the prediction of alternative bio-chemical pathways. Molecular information on genes, proteins, biochemical reactions, mutations, inborn errors and metabolic diseases are available via internet. Based on this information we developed an information retrieval and processing concept combining knowledge about metabolic diseases and biochemical effects.

Genetic studies in Medzev, an isolate in south-eastern Slovakia. 2. Distribution of blood group genetic markers.

Phenotype and gene frequencies of three blood group, four serum protein and seven red cell enzyme polymorphisms were examined in 105 individuals from the population of Medzev, South-Eastern Slovakia. Locus and allele specific tests of homogeneity were calculated in order to obtain the pattern of variation. The results indicate considerable genetic differences between this population and another local population of this region (Chmelnica) as well as between the Medzev population and the total population of Slovakia. The possible reasons of the genetic heterogeneity within Slovakia are discussed.

Prophylactic efficacy of 3-acetyl-4''-isovaleryl tylosin in a Mycoplasma gallisepticum-induced airsacculitis infection.

Formulations of 3-acetyl-4''-isovaleryl tylosin (AIV) were evaluated for oral efficacy in a Mycoplasma gallisepticum (MG) airsacculitis infection. AIV administered by gavage, feed, or water was more effective than tylosin in preventing airsacculitis. An AIV tartrate formulation administered in drinking water to chickens infected with a macrolide-sensitive or macrolide-resistant strain of MG resulted in no detection of mycoplasma in the air sacs and in MG-negative sera.