Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development.

Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.

Real-world healthcare resource utilization related to migraine treatment failure: a panel-based chart review in France, Germany, Italy, and Spain.

Aims: This retrospective chart review examined the six-month migraine-related healthcare resource use (HRU) among European patients who had ≥4 migraine days per month and previously failed at least two prophylactic migraine treatments. Methods: Neurologists, headache specialists, and pain specialists in France, Germany, Italy, and Spain who treated ≥10 patients with migraine in 2017 were recruited (April-June 2018) to extract anonymized patient-level data. Eligible physicians randomly selected charts of up to five adult patients with clinically-confirmed migraine, ≥4 migraine days in the month prior to the index date, and had previously failed at least two prophylactic migraine treatments. Treatment failure was defined as discontinuation due to lack of efficacy and/or tolerability. Demographic and disease characteristics as of the index date, and migraine-related HRU incurred during the 6-month study period, were recorded. Results: A total of 104 physicians contributed 168 charts for patients (63% female). On average, patients were 38 years old and failed 2.3 prophylactic treatments as of the index date. During the study period, 83% of patients had ≥1 outpatient visit for migraine in the physician's office, and 27% went to the ER/A&E. Approximately 5% of patients were hospitalized for migraine, with an average of one hospitalization and an average length of stay of 3 days. Approximately 39% of patients had ≥1 blood test, 22% had ≥1 magnetic resonance imaging, 17% had ≥1 electroencephalogram, and 13% had ≥1 computerized tomography scan. Visits to other healthcare providers were common. Limitations: This study is subject to the limitations of chart review studies, such as errors in data entry. Conclusions: Across four European countries, the HRU burden of migraine among patients who previously failed at least two prophylactic treatments was high, indicating a need for more effective prophylactic treatments to appropriately manage migraine and reduce the HRU burden attributable to this common disorder.

Migraine-related healthcare resource use in the emergency department setting: a panel-based chart review in France, Germany, Italy, and Spain.

Objective: Migraine is a common, disabling condition typically characterized by severe headache, nausea, and/or light and sound sensitivity. This study assessed migraine-related health resource utilization (HRU) occurring in the emergency room/accident & emergency department (ER/A&E) setting among European patients with 4 or more migraine days per month. Methods: Patient-level clinical and HRU data were collected via chart extraction by ER/A&E physicians in France, Germany, Italy, and Spain. Eligible patients had 4 or more migraine days in the month prior to a migraine-related ER/A&E visit and a history of migraine, among other criteria. The index date for each patient was defined as the date of an ER/A&E visit for migraine on or after January 1, 2013. Physician and ER/A&E characteristics, patient and disease characteristics, treatment history, migraine-medication used, and migraine-related HRU (i.e. procedures) during the ER/A&E visit were assessed. Descriptive analyses were conducted in the pooled population, and a sensitivity analysis was performed by country. Results: A total of 467 eligible patient's charts (120 in France, 120 in Germany, 107 in Italy, and 120 in Spain) were provided by 136 physicians (36 in France, 36 in Germany, 28 in Italy, and 36 in Spain). On average, patients spent nearly 8 hours in the ER/A&E. Approximately 82% of patients received a blood test, 62% received an electrocardiography, and 46% received a cranial computerized tomography scan. Despite the majority of patients already using acute or prophylactic treatment upon visiting the ER/A&E, almost all patients were administered or prescribed migraine treatment during the visit. Approximately 21% of patients were admitted to the hospital, and over half of patients were referred to a neurologist or headache specialist. Conclusions: European patients who had four or more migraine days in the month prior to a migraine-related ER/A&E visit had high HRU associated with the visit.