Bacteriophage Administration Reduces the Concentration of Listeria monocytogenes in the Gastrointestinal Tract and Its Translocation to Spleen and Liver in Experimentally Infected Mice

To investigate the efficacy of phage supplementation in reducing pathogen numbers, mice were treated via oral gavage with a Listeria monocytogenes phage preparation (designated ListShield) before being orally infected with L. monocytogenes. The concentrations of L. monocytogenes in the liver, spleen, and intestines were significantly lower (P < .05) in the phage-treated than in the control mice. Phage and antibiotic treatments were similarly effective in reducing the levels of L. monocytogenes in the internal organs of the infected mice. However, the significant weight loss detected in the control and antibiotic-treated groups was not observed in the infected, ListShield-treated mice. Long-term (90 days), biweekly treatment of uninfected mice with ListShield did not elicit detectable changes in the microbiota of their large intestines or deleterious changes in their health. Our data support the potential feasibility of using bacteriophages to control proliferation of L. monocytogenes in mice without affecting commensal microbiota composition

Gut Microbiota Composition and Diversity Before, During, and Two Months After Rifamycin-Based Tuberculosis Preventive Therapy

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention

Chronic Overlapping Pain Conditions and Long-Term Opioid Treatment

OBJECTIVES: One in 5 people in the United States lives with chronic pain. Many patients with chronic pain experience a subset of specific co-occurring pain conditions that may share a common pain mechanism and that have been designated as chronic overlapping pain conditions (COPCs). Little is known about chronic opioid prescribing patterns among patients with COPCs in primary care settings, especially among socioeconomically vulnerable patients. This study aims to evaluate opioid prescribing among patients with COPCs in US community health centers and to identify individual COPCs and their combinations that are associated with long-term opioid treatment (LOT). STUDY DESIGN: Retrospective cohort study. METHODS: We conducted analyses of more than 1 million patients 18 years and older based on electronic health record data from 449 US community health centers across 17 states between January 1, 2009, and December 31, 2018. Logistic regression models were used to assess the relationship between COPCs and LOT. RESULTS: Individuals with COPCs were prescribed LOT 4 times more often than individuals without a COPC (16.9% vs 4.0%). The presence of chronic low back pain, migraine headache, fibromyalgia, or irritable bowel syndrome combined with any of the other COPCs increased the odds of LOT prescribing compared with the presence of a single COPC. CONCLUSIONS: Although LOT prescribing has declined over time, it remains relatively high among patients with certain COPCs and for those with multiple COPCs. These study findings suggest target populations for future interventions to manage chronic pain among socioeconomically vulnerable patients

Prevalent Multimorbidity Combinations Among Middle-Aged and Older Adults Seen in Community Health Centers

BACKGROUND: Multimorbidity (≥ 2 chronic diseases) is associated with greater disability and higher treatment burden, as well as difficulty coordinating self-management tasks for adults with complex multimorbidity patterns. Comparatively little work has focused on assessing multimorbidity patterns among patients seeking care in community health centers (CHCs). OBJECTIVE: To identify and characterize prevalent multimorbidity patterns in a multi-state network of CHCs over a 5-year period. DESIGN: A cohort study of the 2014-2019 ADVANCE multi-state CHC clinical data network. We identified the most prevalent multimorbidity combination patterns and assessed the frequency of patterns throughout a 5-year period as well as the demographic characteristics of patient panels by prevalent patterns. PARTICIPANTS: The study included data from 838,642 patients aged ≥ 45 years who were seen in 337 CHCs across 22 states between 2014 and 2019. MAIN MEASURES: Prevalent multimorbidity patterns of somatic, mental health, and mental-somatic combinations of 22 chronic diseases based on the U.S. Department of Health and Human Services Multiple Chronic Conditions framework: anxiety, arthritis, asthma, autism, cancer, cardiac arrhythmia, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), congestive heart failure, coronary artery disease, dementia, depression, diabetes, hepatitis, human immunodeficiency virus (HIV), hyperlipidemia, hypertension, osteoporosis, post-traumatic stress disorder (PTSD), schizophrenia, substance use disorder, and stroke. KEY RESULTS: Multimorbidity is common among middle-aged and older patients seen in CHCs: 40% have somatic, 6% have mental health, and 24% have mental-somatic multimorbidity patterns. The most frequently occurring pattern across all years is hyperlipidemia-hypertension. The three most frequent patterns are various iterations of hyperlipidemia, hypertension, and diabetes and are consistent in rank of occurrence across all years. CKD-hyperlipidemia-hypertension and anxiety-depression are both more frequent in later study years. CONCLUSIONS: CHCs are increasingly seeing more complex multimorbidity patterns over time; these most often involve mental health morbidity and advanced cardiometabolic-renal morbidity

Curated and Harmonized Gut Microbiome 16S rRNA Amplicon Data From Dietary Fiber Intervention Studies in Humans

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies

Curated and harmonized gut microbiome 16S rRNA amplicon data from dietary fiber intervention studies in humans

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies

Efficacy and safety of levosalbutamol in patients with mild to moderate asthma compared with racemic salbutamol: results of a crossover placebo-controlled study

Aim. Effectiveness and safety of levosalbutamol metered dose inhaler (MDI) in comparison with placebo and salbutamol. Materials and methods. In this multicenter, randomized, placebo-controlled, 3-period crossover study, all asthma patients (n=91) received levosalbutamol (90 mcg), salbutamol (180 mcg), and placebo using standard MDI. Pulmonary function testing – forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) – was performed 45 and 15 minutes before and 5, 10, 15, 30, 60, 90, 120, 180, 240, 300 and 360 minutes after dosing. The primary efficacy endpoint was the baseline-corrected area under FEV1 curve from 0 to 6 hours (AUC(0–6h)). Secondary endpoints were the baseline adjusted FEV1 and FVC peak values, as well as the onset of drug action. Results. The FEV1 AUC0–6 hours analysis confirmed similar bronchodilatory levosalbutamol and salbutamol effect (p=0.595), significantly improved compared with placebo (p0.001). The peak values of FEV1 and FVC after levosalbutamol or salbutamol dosing were similar (p=0.643) and significantly higher compared with placebo group (p0.001). The active therapy effect was observed 5 minutes after dosing and throughout the entire observation period up to 6 hours, however, there was some tendency towards a longer duration of action of levosalbutamol compared to salbutamol. Levosalbutamol was well tolerated by patients; after levosalbutamol dosing twiсе fewer adverse reactions were observed compared to salbutamol. Conclusion. Levosalbutamol at a 90-mcg dose showed efficacy similar to that of salbutamol at a dose of 180 mcg, assosiated with a good safety profile

Fecal Microbiota in Premature Infants Prior to Necrotizing Enterocolitis

Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis (NEC), a common disease in preterm infants. Microbiota development, a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota, can now be studied in preterm infants using powerful molecular tools. Starting with the first stool and continuing until discharge, weekly stool specimens were collected prospectively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g. High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls. After removal of short and low quality reads we retained a total of 110,021 sequences. Microbiota composition differed in the matched samples collected 1 week but not <72 hours prior to NEC diagnosis. We detected a bloom (34% increase) of Proteobacteria and a decrease (32%) in Firmicutes in NEC cases between the 1 week and <72 hour samples. No significant change was identified in the controls. At both time points, molecular signatures were identified that were increased in NEC cases. One of the bacterial signatures detected more frequently in NEC cases (p<0.01) matched closest to γ-Proteobacteria. Although this sequence grouped to the well-studied Enterobacteriaceae family, it did not match any sequence in Genbank by more than 97%. Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC

Advancing cross-national planning and partnership: proceedings from the International Multimorbidity Symposium 2019

The International Multimorbidity Symposium was held in November 2019 at Western University to achieve three main objectives: to discuss progress and findings from various jurisdictions; to facilitate collaboration through group discussion to identify strategies to move multimorbidity research forward; and to create concrete plans to ensure advances in multimorbidity research and knowledge can be achieved through cross-national partnership. This event included keynote presentations, elevator pitch presentations and breakout sessions and there was a total of 35 attendees from eight countries, representing diverse disciplines and training levels. The overall themes arising from the event were: the importance of integrating the study and management of multimorbidity from both the primary care and public health perspectives; meaningful engagement and collaboration with patients and caregivers to understand key dimensions of multimorbidity; the considerable benefit of collaborative international partnerships; and the need to spread and scale innovations for health care systems that can better respond to the complex needs of patients and caregivers who are living with multimorbidity. Finally, it was well-acknowledged among the attendees that expanding the collaboration and discussion among international colleagues via in-person and virtual events will be important to move multimorbidity research forward

High Prevalence of Cefotaxime Resistant Bacteria in Grazing Beef Cattle: A Cross Sectional Study

Although the over-use of antibiotics during food animal production is a potential driver of antimicrobial resistant microorganisms (ARMs), a high prevalence of cefotaxime resistant bacteria (CRB) has been observed in grazing animals raised without antibiotic supplementation. In this cross-sectional study, the prevalence and concentration of CRB in beef cattle on grazing farms were investigated. Fecal samples from the recto-anal junction of cattle (n = 840) and environmental samples (n = 258) were collected from 17 farms in North and Central Florida in the United States, and a survey of farm characteristics, animal husbandry practices, and antibiotic usage was conducted. CRB were detected in fecal samples from 47.4% of all cattle, with the prevalence ranging from 21.1 to 87.5% on farms, and significantly higher (P &lt; 0.001) in calves compared to adult cows (54.1 vs. 41.8%). Environmental samples had a higher prevalence than fecal samples (P &lt; 0.001), with CRB detected in 88.6% of water, 98.7% of soil, and 95.7% of forage samples. Compared to the concentration (log CFU/g) of CRB in fecal samples (2.95, 95% CI: 2.89, 3.02), the concentration of CRB was higher (P &lt; 0.001) in soil and forage samples (5.37, 95% CI: 5.16, 5.57) and lower (P &lt; 0.001) in water samples (1.08, 95% CI: 0.82, 1.36). Soil microbiota from farms with high prevalence of CRB clustered closer together and the proportion of Phylum Proteobacteria was higher on farms with high prevalence of CRB resistance. Large farming operations were associated with a 58% higher likelihood of CRB detection in fecal samples. Regular cleaning of drinking troughs and the addition of ionophores to feed were associated with CRB reduction in fecal samples. Taken together, the widespread of CRB into both cattle seldom treated with cephalosporin antibiotics and the surrounding environment suggests the environment is a natural source of antimicrobial resistance in beef cattle