BACKGROUND AIMS: Glutamine supplementation has been associated with reduced mortality, infections and hospital length of stay in critically ill patients and patients undergoing major surgery. We carried out a meta-analysis to examine randomized clinical trial (RCT)-based evidence of these effects. METHODS: Based on a systematic database search, RCTs published since 1990 were included if they evaluated the effect of parenteral glutamine supplementation against a background of parenteral nutrition. Enteral (tube) feeding in a proportion of patients was allowable. Information on RCT methodology, quality and outcomes was extracted. Random effects meta-analysis followed the DerSimonian-Laird approach. RESULTS: Forty RCTs were eligible for meta-analysis. Parenteral glutamine supplementation was associated with a non-significant 11% reduction in short-term mortality (RR = 0.89; 95% CI, 0.77-1.04). Infections were significantly reduced (RR = 0.83; 95% CI, 0.72-0.95) and length of stay was 2.35 days shorter (95% CI, -3.68 to -1.02) in the glutamine arms. Meta-analysis results were strongly influenced by one recent trial. An element of publication bias could not be excluded. CONCLUSION: Parenteral glutamine supplementation in severely ill patients may reduce infections, length of stay and mortality, but substantial uncertainty remains. Unlike previous meta-analyses, we could not demonstrate a significant reduction in mortality.

Anthracycline-induced cardiotoxicity (ACT) is a well-known serious adverse drug reaction leading to substantial morbidity. The purpose of this study was to assess ACT occurrence and clinical and genetic risk factors in early breast cancer patients. In 6 genes of interest (ABCC1, ABCC2, CYBA, NCF4, RAC2, SLC28A3), 10 single nucleotide polymorphisms (SNPs) involved in ACT were selected based on a literature search. Eight hundred and seventy-seven patients treated between 2000 and 2010 with 3-6 cycles of (neo) adjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC) were genotyped for these SNPs using Sequenom MassARRAY. Main outcome measures were asymptomatic decrease of left ventricular ejection fraction (LVEF) > 10 % and cardiac failure grade 3-5 (CTCAE 4.0). To evaluate the impact of these 10 SNPs as well as clinical factors (age, relative dose intensity of epirubicin, left-sided radiotherapy, occurrence of febrile neutropenia, and planned and received cycles of epirubicin) on decrease of LVEF and cardiac failure, we performed uni- and multivariable logistic regression analysis. Additionally, exploratory analyses including 11 additional SNPs related to the metabolism of anthracyclines were performed. After a median follow-up of 3.62 years (range 0.40-9.60), a LVEF decline of > 10 % occurred in 153 patients (17.5 %) and cardiac failure in 16 patients (1.8 %). In multivariable analysis, six cycles of FEC compared to three cycles received and heterozygous carriers of the rs246221 T-allele in ABCC1 relative to homozygous carriers of the T-allele were significantly associated with LVEF decline of > 10 % (OR 1.3, 95 % CI 1.1-1.4, p < 0.001 and OR 1.6, 95 % CI 1.1-2.3, p = 0.02). Radiotherapy for left-sided breast cancer was associated with cardiac failure (OR 3.7, 95 % CI 1.2-11.5, p 0.026). The other 9 SNPs and clinical factors tested were not significantly associated. In our exploratory analysis, no other SNPs related to anthracycline metabolism were retained in the multivariate model for prediction of LVEF decline. ACT in breast cancer patients is related to number of received cycles of epirubicin and left-sided radiotherapy. Additional studies should be performed to independently confirm the potential association between rs246221 in ABCC1 and LVEF.

In clinical trials, sofosbuvir showed high antiviral activity in patients infected with hepatitis C virus (HCV) across all genotypes. We aimed to determine the cost-effectiveness of sofosbuvir-based treatment compared to current standard treatment in mono-infected patients with chronic hepatitis C (CHC) genotypes 1–4 in Switzerland. Cost-effectiveness was modelled from the perspective of the Swiss health care system using a lifetime Markov model. Incremental cost-effectiveness ratios (ICERs) used an endpoint of cost per quality-adjusted life year (QALY) gained. Treatment characteristics, quality of life, and transition probabilities were obtained from published literature. Country-specific model inputs such as patient characteristics, mortality and costs were obtained from Swiss sources. We performed extensive sensitivity analyses. Costs and effects were discounted at 3% (range: 0–5%) per year. Sofosbuvir-containing treatment in mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1–4 showed ICERs between CHF 10,337 and CHF 91,570 per QALY gained. In subgroup analyses, sofosbuvir dominated telaprevir- and boceprevir-containing treatment in treatment-naïve genotype 1 cirrhotic patients. ICERs of sofosbuvir were above CHF 100,000 per QALY in treatment-naïve, interferon eligible, non-cirrhotic patients infected with genotypes 2 or 3. In deterministic and probabilistic sensitivity analyses, results were generally robust. From a Swiss health care system perspective, treatment of mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1–4 with sofosbuvir-containing treatment versus standard treatment would be cost-effective if a threshold of CHF 100,000 per QALY was assumed.

Pegfilgrastim reduced the incidence of FN and CIN compared with no prophylaxis. Most studies showed better efficacy and effectiveness for pegfilgrastim than filgrastim. Efficacy and safety profiles of lipegfilgrastim and balugrastim were similar to pegfilgrastim.

Model input parameters such as age at vaccination, vaccine costs, HZ incidence, PHN length and duration of vaccine efficacy had a great impact on the estimated cost effectiveness of HZ vaccination. To compare the results of different cost-effectiveness studies of HZ vaccination, uniform methods should be used and the most important input parameters used for the different models should be critically assessed.