Background Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches. Methods We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as firstline or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR. Findings We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0•42; 95% credible interval [CrI] 0•25-0•70), ribociclib plus letrozole (0•43; 0•24-0•77), abemaciclib plus anastrozole or letrozole (0•42; 0•23-0•76), palbociclib plus fulvestrant (0•37; 0•23-0•59), ribociclib plus fulvestrant (0•48; 0•31-0•74), abemaciclib plus fulvestrant (0•44; 0•28-0•70), everolimus plus exemestane (0•42; 0•28-0•67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0•39; 0•22-0•66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8•95; 95% CrI 1•03-76•92). Interpretation In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free surv...

OBJECTIVE. The relationship between metformin accumulation and lactate increase is still debated. This observational case series aims to evaluate the correlation of metformin plasma levels with the pH, lactate and creatinine levels, and with the mortality rate in selected patients with metformin accumulation confirmed through metformin plasma concentration detection at hospital admission. MATERIAL AND METHODS. All cases of lactic acidosis (pH, ≤ 7.35; arterial lactate, ≥ 5 mmol/L) related to metformin accumulation (plasma level ≥ 4 mcg/mL) from 2007 to 2011 were retrospectively reviewed. Erroneous ingestion and voluntary overdoses were excluded. Epidemiological, medical history, clinical and laboratory data were evaluated in all cases. RESULTS. Sixty-six patients were included. Thirty-one patients (47%) had contraindication to therapy with metformin. All patients showed severe lactic acidosis (pH, 6.91 ± 0.18; lactate, 14.36 ± 4.90 mmol/L) and acute renal failure (creatinine, 7.24 ± 3.29 mg/dL). The mean metformin plasma concentration was 40.68 ± 27.70 mcg/mL. Metformin plasma concentrations showed a correlation, statistically significant even if not strong, with creatinine (p = 0.002, R = 0.37), pH (p < 0.0001, R = - 0.43) and plasma lactate levels (p = 0.001, R = 0.41). Sixty-two (94%) underwent dialysis. Early mortality (before discharge from ICU) was 26% (17 cases). Lactate and metformin concentrations had mean levels not statistically different in surviving and deceased patients. CONCLUSIONS. Patients on chronic therapy with metformin may develop a mitochondrial-related toxicity that should be considered when patients present with lactic acidosis, renal failure, and frequently, a medical history of gastrointestinal manifestations during the days preceding the hospital admission. The correlation between metformin plasma concentrations and creatinine, pH, and lactate levels seems to be related to the mechanism of action (inhibition of complex I of the mitochondrial respiratory chain) and to the kinetic properties (high distribution volume and low protein binding) of the drug. The relevant early mortality seems not correlated with the levels of metformin or lactates: this could be due to the possible role of concurrent illness even if, such as for the relationships with lactate and creatinine, a more proper toxicological evaluation could be obtained by assessing metformin erythrocyte concentrations instead of the plasmatic ones.

BackgroundIron deficiency is very common in a number of medical conditions. Ferric carboxymaltose is a new stable iron preparation that can be administered in single infusions over short periods of time. The aim of this study was to conduct a systematic review of randomised controlled trials (RCTs) regarding the efficacy and safety of the novel complex compared with other iron formulations. In addition, the feasibility of a network meta-analysis for indirect comparisons was investigated.MethodsA systematic literature review was performed for published RCTs on the use of ferric carboxymaltose in iron deficiency between July and October 2014. Indirect comparisons were also addressed using terms referring to competing iron formulations. We further supported the qualitative results of the systematic review by a network meta-analysis that allows pooling the evidence around different intervention outcomes in the absence of trials involving a direct comparison.ResultsThe initial search yielded 1027 citations, which was decreased to 21 studies eligible for inclusion in the review. Studies were heterogeneous in the number of patients randomised, iron deficiency-related conditions addressed, trial inclusion criteria, time horizon, treatment dosage and outcomes assessed. Six studies with the same time horizon (i.e. 6 weeks) were included in the network meta-analysis. Considering the differences between final and initial outcome values for each iron formulation, the mean difference of these differences (delta) was estimated for each couple of treatments involving ferric carboxymaltose. Significant improvements in serum ferritin (µg/l) were obtained with ferric carboxymaltose compared to oral iron (delta 172.8; 95 % CI 66.7–234.4) and in haemoglobin (g/dl) with respect to ferric gluconate (delta 0.6; 95 % CI 0.2–0.9), oral iron (delta 0.8; 95 % CI 0.6–0.9) and placebo (delta 2.1; 95 % CI 1.2–3.0).ConclusionsAll currently available intravenous iron preparations appear to be safe and effective, but ferric carboxymaltose seems to provide a better and quicker correction of haemoglobin and serum ferritin levels in iron-deficient patients.

No abstract

Purpose Antimicrobial resistance (AMR) is one of the major threats to human health, and the high frequency of resistant pathogens in the hospital environment can contribute to the transmission of difficult-to-treat health care-associated infections (HAIs). We recently reported that, compared with conventional chemical cleaning, the use of a microbial-based sanitation strategy (Probiotic Cleaning Hygiene System [PCHS]) was associated with remodulation of hospital microbiota and reduction of HAI incidence. Here, we aimed to analyze the impact of PCHS on AMR and related effects, such as HAI-associated antimicrobial drug consumption and costs. Patients and methods Five Italian hospitals, enrolled in a multicenter study where conventional sanitation methods were replaced with PCHS, were included in the analysis. The study period included a 6-month observation for each sanitation type. Surface microbiota AMR was analyzed using microarray, nested PCR, antibiogram, and microdilution tests. Drug consumption data and related costs were obtained from the medical records of all hospitalized patients affected by HAIs. Results PCHS use was associated with up to 99% decrease of the AMR genes harbored by surface hospital microbiota, independently of the resistance types originally present in each individual setting ( P c <0.01). Functional assays confirmed the molecular data, demonstrating a 33%–100% decrease of resistant strains depending on the antibiotic type. Antimicrobial drug consumption associated with HAI onset showed a global 60.3% decrease, with a 75.4% decrease of the associated costs. Conclusion The spread of AMR in the hospital environment can be limited by the use of sanitation methods to remodulate the hospital microbiota, leading to lower antimicrobial consumption and costs. This approach might be considered as part of broader infection prevention and control strategies.

From an Italian health care service perspective, TARE could be a cost-effective strategy in comparison with sorafenib for patients with intermediate or advanced HCC. The results from forthcoming randomized controlled trials comparing TARE with sorafenib will be able to confirm or reject the validity of this preliminary evaluation. In the meantime, decision makers can use these results to control and coordinate the diffusion of the technology.

Fresenius/Neovii Biotech.

BackgroundIntermittent catheterisation is the method of choice for the management of bladder dysfunctions. Different urinary catheters are available, but there is conflicting evidence on which type of catheter is best. The present study provides an objective evaluation of the clinical effectiveness of different subsets of urinary catheters.MethodsA systematic literature review was performed for published RCTs regarding hydrophilic coated and PVC (standard) catheters for intermittent catheterisation. Separate meta-analyses were conducted to combine data on frequencies of urinary tract infections (UTIs) and haematuria. Two separate analyses were performed, including or excluding reused standard catheters.ResultsSeven studies were eligible for inclusion in the review. The meta-analyses exploring UTI frequencies showed a lower risk ratio associated with hydrophilic catheters in comparison to standard ones (RR = 0.84; 95% CI, 0.75–0.94; p = 0.003). Results for the “reuse” scenario were consistent with the ones related to “single-use” scenario in terms of frequency of UTIs. The meta-analyses exploring haematuria were not able to demonstrate any statistically significant difference between hydrophilic catheters in comparison to standard ones.ConclusionsThe findings confirm previously reported benefits of hydrophilic catheters but a broader evaluation that takes into account also patient preferences, compliance of therapy, quality of life and costs would be needed to assess the economic sustainability of these advanced devices.Electronic supplementary materialThe online version of this article (doi:10.1186/s12894-016-0191-1) contains supplementary material, which is available to authorized users.