Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection.

INTRODUCTION: Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020. https://doi.org/10.1007/s10620-020-06185-7 ) present the clinical outcomes for different FMT methodologies. However, to understand, compare, and contextualize outcomes, this heterogeneity in methods and reporting must be understood. METHODS: We performed a literature review of randomized controlled trials (RCTs) of FMT for rCDI to evaluate heterogeneity among trials. A methodical search between January 2010 and May 2019 of Medline, Embase, and Cochrane was conducted for studies investigating FMT in adults with rCDI. RCTs were evaluated for a variety of methodological and reporting criteria. RESULTS: Eight RCTs were identified, wherein 14 different FMT preparations were considered (each with distinct protocols for processing, storage, administration, and dosing). Sample sizes were generally small, with only two studies performing FMT in more than 100 patients. Three studies used non-FMT controls (vancomycin), while the remaining compared FMT with differing routes of administration or formulations. Across the identified studies, there was no standardized manner for reporting the timing of the FMT procedure. All studies tracked adverse events; however, follow-up periods were limited. CONCLUSIONS: Considerable variability exists among RCTs, with marked differences in study design, control groups, and outcome assessment. Lack of a standard-of-care control in many trials may impact reproducibility of FMT trial outcomes in patients with rCDI. Widespread use of FMT for rCDI is still investigational; therefore, these foundational studies provide opportunities to optimize future trials.

Real-world experience with intravaginal culture using INVOCELL: an alternative model for infertility treatment.

OBJECTIVE: To describe the current practice indications, methodology, and outcomes from a real-world experience of intravaginal culture (IVC) using INVOCELL. DESIGN: A descriptive study outlining real-world experience with INVOCELL that addresses patient selection, ovarian stimulation, embryology laboratory practices, and outcomes. SETTING: Five fertility centers in Missouri, Texas, North Carolina, South Carolina, and Virginia. PATIENTS: Four hundred sixty-three patients undergoing 526 cycles. INTERVENTION: IVC using INVOCELL. MAIN OUTCOME MEASURES: Cumulative pregnancy rate and live births. Secondary outcomes of interest included percent good quality embryos. RESULTS: IVC with INVOCELL was primarily used in women <38 years with anti-Mullerian hormone level >0.8 ng/mL. The mean numbers of retrieved oocytes ranged from 9.2 to 16. Mean numbers of oocytes and sperm-injected oocytes loaded per INVOCELL ranged from a mean of 6.4-9.5 with a reported maximum of 34 oocytes loaded into the device. Most (95%) of the embryos were transferred on day 5. The mean blastocyst recovery per oocyte loaded into the device ranged from 19% to 34%; mean cumulative live birth plus ongoing pregnancy rates ranged from 29% to 53% per cycle start and 40% to 61% per transfer. CONCLUSIONS: This study of IVC using INVOCELL as an alternative model for infertility treatment confirms its utility as a viable alternative to standard incubator-based in vitro fertilization. The technology is compatible within the current framework of practice patterns and, when appropriately used, results in acceptable blastocyst recovery and live birth rates. Further use of INVOCELL in other clinical situations is warranted.

Insights from Real-World Analysis of Treatment Patterns in Patients with Newly Diagnosed Knee Osteoarthritis.

BACKGROUND: Several nonpharmacologic and pharmacologic treatments are available for the management of knee osteoarthritis (OA)-related pain and for improving functionality; however, clinical guideline recommendations vary on their use. OBJECTIVE: To compare the treatment patterns in a real-world setting versus the guideline recommendations for the treatment of newly diagnosed patients with knee OA. METHODS: This retrospective analysis used data from the electronic health records of the Geisinger Health System between January 1, 2010, and December 2018 to identify adults with newly diagnosed knee OA who had not received previous therapy with intra-articular corticosteroids, opioids, intra-articular hyaluronic acid, or prescription nonsteroidal anti-inflammatory drugs (NSAIDs). Eligible patients were evaluated for the mutually exclusive treatment categories after diagnosis, including prescription NSAIDs, intra-articular corticosteroids, intra-articular hyaluronic acid (specifically an intra-articular bioengineered hyaluronic acid), opioids, physical therapy, bracing, and total knee arthroplasty. These 7 treatment categories were evaluated for utilization patterns in the real-world setting. RESULTS: A total of 8776 patients with a new diagnosis of knee OA were identified; 88.2% of them received 1 of the 7 evaluated treatments. The most frequently prescribed first treatment was intra-articular corticosteroids (26%), followed by opioids (17.6%), and intra-articular bioengineered hyaluronic acid (14.9%). The most often prescribed second treatment was opioids (15.8%), followed by physical therapy (14%), NSAIDs (11.8%), and intra-articular bioengineered hyaluronic acid (9.6%). Of note, 22.9% of the patients received only 1 evaluated therapy during the study period and did not receive a second treatment. CONCLUSIONS: Real-world treatment patterns in patients with newly diagnosed knee OA indicate that prescribers are using the spectrum of the available therapies that, at times, are different from the current treatment guideline recommendations.

Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis.

OBJECTIVE: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. METHODS: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18-64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). RESULTS: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. CONCLUSIONS: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis.

Aims: This study aimed to evaluate all-cause economic outcomes, healthcare resource utilization (HRU), and costs in patients with Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) using commercial claims from a large database representing various healthcare settings.Materials and methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus database was conducted for patients aged 18-64 years with CDI episodes requiring inpatient stay with CDI diagnosis code or an outpatient medical claim for CDI plus a CDI treatment. Index CDI episodes occurred between 1 January 2010 and 30 June 2017, including only those where patients were observable 6 months before and 12 months after the index episode. Each CDI episode was followed by a 14-d claim-free period. rCDI was defined as another CDI episode within an 8-week window following the claim-free period. HRU, all-cause direct medical costs and time to rCDI were calculated over 12 months and stratified by number of rCDI episodes.Results: A total of 46,571 patients with index CDI were included. Mean time from one CDI episode to the next was approximately 1 month. In the 12-month follow-up period, those with no recurrence had 1.4 inpatient visits per person and those with 3 or more recurrences had 5.8. Most patients with 3 or more recurrences had 2 or more hospital admissions. The mean annual, total all-cause direct medical costs per patient were $71,980 for those with no recurrence and $207,733 for those with 3 or more recurrences.Limitations: The study included individuals 18-64 years only. A stringent definition of rCDI was used, which may have underestimated the incidence of rCDI.Conclusions: CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. Timing of recurrences can be predictable, providing a window of opportunity for interventions. Prevention of multiple rCDI appears essential to reduce healthcare costs.