Intestinal microbiota plays an important role in human health, and its composition is determined by several factors, such as diet and host genotype. However, thus far it has remained unknown which host genes are determinants for the microbiota composition. We studied the diversity and abundance of dominant bacteria and bifidobacteria from the faecal samples of 71 healthy individuals. In this cohort, 14 were non-secretor individuals and the remainders were secretors. The secretor status is defined by the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucus and other secretions. It is determined by fucosyltransferase 2 enzyme, encoded by the FUT2 gene. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. PCR-DGGE and qPCR methods were applied for the intestinal microbiota analysis. Principal component analysis of bifidobacterial DGGE profiles showed that the samples of non-secretor individuals formed a separate cluster within the secretor samples. Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals. The non-secretor individuals lacked, or were rarely colonized by, several genotypes related to B. bifidum, B. adolescentis and B. catenulatum/pseudocatenulatum. In contrast to bifidobacteria, several bacterial genotypes were more common and the richness (p<0.04) of dominant bacteria as detected by PCR-DGGE was higher in the non-secretor individuals than in the secretor individuals. We showed that the diversity and composition of the human bifidobacterial population is strongly associated with the histo-blood group ABH secretor/non-secretor status, which consequently appears to be one of the host genetic determinants for the composition of the intestinal microbiota. This association can be explained by the difference between the secretor and non-secretor individuals in their expression of ABH and Lewis glycan epitopes in the mucosa.

An International Consensus Conference (ICC) on PBM was held in 2018 to develop evidence‐based clinical and research recommendations for preoperative anaemia, red blood cell (RBC) transfusion thresholds for adults and implementation of PBM programmes. An international scientific committee (SC) defined 17 Population‐Intervention‐Comparison‐Outcome (PICO) questions for the three topics preoperative anaemia, red blood cell (RBC) transfusion thresholds for adults and PBM implementation. Based on these questions, an extensive literature search was conducted in four biomedical databases. The GRADE framework (= grading of recommendations, assessment, development and evaluation) was used to develop a systematic approach to the presentation of evidence summaries and for making clinical recommendations. Three expert panels (EP) consisting of clinicians, scientists, nurses, patient representatives and methodologists were established and used these methods to develop recommendations driven by published evidence. Out of more than 17 500 literature citations, data from 145 studies were incorporated. The expert panel for preoperative anaemia developed 4 clinical and 3 research recommendations. A strong recommendation advices early detection and management of preoperative anaemia before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations have been formulated. Two strong clinical recommendations for RBC transfusion thresholds comprise a haemoglobin concentration of <7 g/dl for critically ill, but clinical stable adult intensive care patients independent of septic shock and <7·5 g/dl for adults undergoing cardiac surgery. For the implementation of PBM programmes, 2 clinical and 3 research recommendations were developed. Research recommendations were formulated as encouragement of new studies to answer open questions. Due to the relative paucity of strong evidence‐based answers in current publications to the 17 PICO questions, additional research, an international consensus for accepted definitions and Hb thresholds as well as clinically meaningful end‐points for clinical studies are necessary. The 2018 PBM ICC defined the current status of PBM evidence and established 10 clinical and 12 research recommendations for preoperative anaemia, RBC transfusion thresholds for adults and implementation of PBM programmes.

IMPORTANCE Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. OBJECTIVE To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. EVIDENCE REVIEWThe scientific committee developed 17 Population/Intervention/ Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018.FINDINGS From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization. CONCLUSIONS AND RELEVANCEThe 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

Phenothiazines have repeatedly been found to be associated with cases of sudden death, but the issue of causality has remained controversial. A survey of medicolegal autopsies performed in Finland over a 3-year period revealed that sudden unexpected deaths of 31 women (mean age 44 years, range 25-69) and 18 men (mean age 40 years, range 26-62) were associated with either the use of antipsychotic or antidepressant drugs. Therapeutic use of phenothiazines was documented in all but 3 of these 49 cases and thioridazine was involved in over half of them. Thus, whereas thioridazine was the only antipsychotic drug associated with 15 cases, only 5 cases were associated with any of the other antipsychotic or antidepressant drugs. The differences between the subgroups of psychotropic drugs remained clear after adjustment according to the respective data on drug use in the population. Although there are several uncontrolled confounding factors, the overrepresentation of phenothiazines, especially thioridazine, among psychiatric patients who died suddenly is striking and, taken together with their well-established arrhythmogenic effects, warrants further attention.

Interaction between erythromycin and midazolam was investigated in two double-blind, randomized, crossover studies. In the first study, 12 healthy volunteers were given 500 mg erythromycin three times a day or placebo for 1 week. On the sixth day, the subjects ingested 15 mg midazolam. In the second study, midazolam (0.05 mg/kg) was given intravenously to six of the same subjects, after similar pretreatments. Plasma samples were collected, and psychomotor performance was measured. Erythromycin increased the area under the midazolam concentration-time curve after oral intake more than four times (p < 0.001) and reduced clearance of intravenously administered midazolam by 54% (p < 0.05). In psychomotor tests (e.g., saccadic eye movements), the interaction between erythromycin and orally administered midazolam was statistically significant (p < 0.05) from 15 minutes to 6 hours. Metabolism of both erythromycin and midazolam by the same cytochrome P450IIIA isozyme may explain the observed pharmacokinetic interaction. Prescription of midazolam for patients receiving erythromycin should be avoided or the dose of midazolam should be reduced by 50% to 75%.