Spine Tango registry data collection in a conservative spinal service: a feasibility study.

PURPOSE: The study reports the feasibility of implementing routine registry data collection and sustaining a high rate of data capture within a secondary care spinal osteopathy service, using the Spine Tango Conservative registry data collection tool (STC) with multiple patient-reported outcome measures (PROMs): Oswestry Disability Index (ODI), Neck Disability Index (NDI), COMI Low Back Conservative, COMI Neck Conservative and EQ-5D-3L. METHODS: Data collection rates were studied during the implementation of a registry data collection project from October 2011 to June 2015. The primary outcome was completion rate of PROMs and the STC, measured as a percentage of total expected data collection. Descriptive statistics were used to illustrate completion rates by year, age group, sex, region of spinal complaint, baseline ODI or NDI score and number of PROMs required to complete the data set. RESULTS: Data were collected on 349 patients. Overall data collection rates increased from 54.8 % in January-June 2012 to 90.4 % in January-June 2015. The percentage of fully completed data sets was lower in the patient group required to complete 4-5 PROMs at each data collection point (15.4 %) than it was in the patient group required to complete 2-3 PROMs (37.4 %). Other comparisons showed no clear patterns. CONCLUSIONS: Our analysis shows that a high rate of data capture can be sustained in a clinical setting using the STC and multiple PROMs. However, increasing the burden of data collection on patients and practitioners was associated with increased data loss. We describe measures taken to reduce data loss in the future and to increase the efficiency of the data collection project.

Novel, non-colonizing, single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo.

BACKGROUND: The Centers for Disease Control and Prevention estimate that Clostridioides difficile (C. difficile) causes half a million infections (CDI) annually and is a major cause of total infectious disease death in the United States, causing inflammation of the colon and potentially deadly diarrhea. We recently reported the isolation of ADS024, a Bacillus velezensis (B. velezensis) strain, which demonstrated direct in vitro bactericidal activity against C. difficile, with minimal collateral impact on other members of the gut microbiota. In this study, we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models. AIM: To investigate the in vivo efficacy of B. velezensis ADS024 in protecting against CDI challenge in mouse models. METHODS: To mimic disruption of the gut microbiota, the mice were exposed to vancomycin prior to dosing with ADS024. For the mouse single-dose study, the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h, 8 h, and 24 h after a single oral dose of 5 × 108 colony-forming units (CFU)/mouse of freshly grown ADS024. The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024, and a group that was not pre-dosed with vancomycin and received a single dose of ADS024. The ADS024 colonies [assessed by quantitative polymerase chain reaction (qPCR) using ADS024-specific primers] were counted on agar plates. For the 28-d miniature swine study, qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5 × 109 CFU for 28 consecutive days, followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota. Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI: Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice, and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024. C. difficile challenge was performed 24 h after the start of ADS024 exposure. To model the human distal colon, an anerobic fecal fermentation system was used. MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment. To assess the potential of ADS024 to be a source of antibiotic resistance, its susceptibility to 18 different antibiotics was tested. RESULTS: In a mouse model of CDI challenge, single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C. difficile pathogen-induced disease. ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine. In a 28-d repeat-dose study in miniature swine, ADS024 was not detected in fecal samples using plating and qPCR methods. Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota, similarly to the in vivo studies performed in miniature swine. Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested, while in silico testing revealed a low potential for off-target activity or virulence and antibiotic-resistance mechanisms. CONCLUSION: Our findings, demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models, support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.

Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities.

Clostridioides difficile infection (CDI) remains a significant health threat worldwide. C. difficile is an opportunistic, toxigenic pathogen that takes advantage of a disrupted gut microbiome to grow and produce signs and symptoms ranging from diarrhea to pseudomembranous colitis. Antibiotics used to treat C. difficile infection are usually broad spectrum and can further disrupt the commensal gut microbiota, leaving patients susceptible to recurrent C. difficile infection. There is a growing need for therapeutic options that can continue to inhibit the outgrowth of C. difficile after antibiotic treatment is completed. Treatments that degrade C. difficile toxins while having minimal collateral impact on gut bacteria are also needed to prevent recurrence. Therapeutic bacteria capable of producing a range of antimicrobial compounds, proteases, and other bioactive metabolites represent a potentially powerful tool for preventing CDI recurrence following resolution of symptoms. Here, we describe the identification and initial characterization of ADS024 (formerly ART24), a novel therapeutic bacterium that can kill C. difficile in vitro with limited impact on other commensal bacteria. In addition to directly killing C. difficile, ADS024 also produces proteases capable of degrading C. difficile toxins, the drivers of symptoms associated with most cases of CDI. ADS024 is in clinical development for the prevention of CDI recurrence as a single-strain live biotherapeutic product, and this initial data set supports further studies aimed at evaluating ADS024 in future human clinical trials.

First evidence of production of the lantibiotic nisin P.

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of two Streptococcus species, albeit with no confirmed evidence of production. Here we describe Streptococcus agalactiae DPC7040, a human faecal isolate, which exhibits antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both the fully modified peptide and a variant without rings B and E being identified. Additionally, we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that of nisin A and its antimicrobial effect in a faecal fermentation in comparison with nisin A and H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose a link between this reduced activity and the peptide structure.

Bacteriocin production: a relatively unharnessed probiotic trait?

Probiotics are "live microorganisms which, when consumed in adequate amounts, confer a health benefit to the host". A number of attributes are highly sought after among these microorganisms, including immunomodulation, epithelial barrier maintenance, competitive exclusion, production of short-chain fatty acids, and bile salt metabolism. Bacteriocin production is also generally regarded as a probiotic trait, but it can be argued that, in contrast to other traits, it is often considered a feature that is desirable, rather than a key probiotic trait. As such, the true potential of these antimicrobials has yet to be realised.

Cauda equina syndrome: factors affecting long-term functional and sphincteric outcome.

STUDY DESIGN: Retrospective cohort study with prospective clinical follow-up. OBJECTIVE: To determine the factors that influence outcome after surgery for cauda equina syndrome (CES). SUMMARY OF BACKGROUND DATA: CES is a rare but serious consequence of lumbar disc prolapse and can have devastating long-lasting neurologic consequences. The timing of surgical decompression remains controversial. METHODS: Fifty-six patients with evidence of a sphincteric disturbance who underwent urgent surgery were identified and invited to follow-up. The outcome measures comprised history and examination and several validated self-assessment questionnaires. RESULTS: Forty-two patients (78%) attended with a mean follow-up of 60 months (range, 25-114 months). Mean age at onset was 41 years (range, 24-67 years) with 23 males and 19 females. Twenty-six patients were operated on within 48 hours of onset of sphincteric symptoms; 5 of these were within 24 hours. Acute onset of sphincteric symptoms and the time to operation did not influence the outcomes. Leg weakness at onset persisted in a significant number of patients at follow-up (P < 0.005). Urinary disturbance at presentation did not affect the outcomes. At follow-up, significantly more females had urinary incontinence (P < 0.005). Bowel dysfunction at presentation was associated with sexual problems at follow-up (P < 0.005). The 13 patients who failed their post operative trial without catheter had worse outcomes. The SF-36 scores at follow-up were reduced compared with age-matched controls in the population. The mean ODI was 29, Low Back Outcome Score 42, and VAS 4.5. The time elapsed from operation to follow-up was not found to influence the outcomes. CONCLUSIONS: In our series, the symptom duration before operation and the speed of onset do not affect the outcome more than 2 years after surgery. Based on the SF-36, ODI, and Low Back Outcome Scores, patients who have had CES do not return to a normal status.

ISSLS prize winner: cost-effectiveness of two forms of circumferential lumbar fusion: a prospective randomized controlled trial.

STUDY DESIGN: Economic evaluation alongside a prospective, randomized controlled trial from a secondary care National Health Service (NHS) perspective. OBJECTIVE: To determine the cost-effectiveness of titanium cages (TC) compared with femoral ring allografts (FRA) in circumferential lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: A randomized controlled trial has shown the use of TC to be clinically inferior to the established practice of using FRA in circumferential lumbar fusion. Health economic evaluation is urgently needed to justify the continued use of TC, given that this treatment is less effective and, all things being equal, is assumed more costly than FRA. METHODS: Eighty-three patients were randomly allocated to receive either the TC or FRA as part of a circumferential lumbar fusion between 1998 and 2002. NHS costs related to the surgery and revision surgery needed during the trial period were monitored and adjusted to the base year (2005-2006 Pounds Sterling). The Short Form-6D (SF-6D) was administered before surgery and at 6, 12 and 24 months in order to elicit patient utility and subsequently Quality-Adjusted Life Years (QALYs) for the trial period. Return to paid employment was also monitored. Bootstrapped mean differences in discounted costs and benefits were generated in order to explore cost-effectiveness. RESULTS: A significant cost difference of pound 1950 (95% CI, pound 849 to pound 3145) in favor of FRA was found. Mean QALYs per patient over the 24-month trial period were 0.0522 (SD, 0.0326) in the TC group and 0.1914 (SD, 0.0398) in the FRA group, producing a significant difference of -0.1392 (95% CI, -0.2349 to -0.0436). With regard to employment, incremental productivity costs were estimated at pound 185,171 in favor of FRA. CONCLUSION: From an NHS perspective, the trial data show that TC is not cost-effective in circumferential lumbar fusion. The use of FRA was both cheaper and generated greater QALY gains. In addition, FRA patients reported a greater return to work rate.

Blood audit evidenced-based cross-match requesting for lumbar spine surgery.

STUDY DESIGN: Complete audit cycle. OBJECTIVE: Radical overhaul of the blood ordering practices made by the spinal surgery department, in order to maximize the efficient use of blood products. SUMMARY OF BACKGROUND DATA: Spinal surgeons request blood-based on historical practice and not evidence. Blood is a scarce resource. Provision relies on voluntary donations from the general population. However, the donor population has been reduced because of the risks of variant Creutzfeldt-Jakob disease. Hence, the responsibility rests with clinicians to optimize their management of blood. METHODS: The spinal surgery department database was accessed to identify all patients who underwent elective lumbar spine operations (excluding deformity) during 2002 to 2003. These records were then cross-referenced with the blood transfusion department database. From the results the cross-match to transfusion (C:T) ratios and transfusion indexes (TI) were calculated for the procedures. A new tariff was agreed between the surgeons, anesthetists, and transfusion department. This was then audited prospectively. RESULTS: There were 664 cross-match requests made during 2002 to 2003, and only 40 U was transfused. This gave a C:T ratio of 16.6:1. The prospective audit resulted in only 58 U being cross-matched and 5 were transfused. This reduced the C:T ratio to 11.5:1. CONCLUSION: Implementing evidence based cross-match protocols can make significant savings in time, manpower, and money.