Clinical burden of recurrent Clostridioides difficile infection in the medicare population: A real-world claims analysis.

Objective: To describe 12-month outcomes for beneficiaries in the 100% Medicare Fee-for-Service (FFS) population with primary and recurrent Clostridioides difficile infection (CDI). Design: A retrospective, descriptive, cohort study of CDI claims from the 100% Medicare FFS population, with a first CDI diagnosis between January 1, 2010, and December 31, 2016. Setting: Any US-based provider that submitted inpatient or outpatient CDI diagnosis claims to Medicare FFS. Patients: The study included patients aged ≥65 years with continuous enrollment in Medicare Parts A, B, and D during 12 months before and 12 months after the index period. Methods: The number of CDI and recurrent (rCDI) episodes, healthcare resource utilization, treatments, complications, and procedures were calculated for pre-index and follow-up periods. The data were stratified by number of rCDI episodes (ie, no rCDI, 1 rCDI, 2 rCDI, and ≥3 rCDI). Results: Of 268,762 patients with an index CDI, 34.7% had at least 1 recurrence. Of those who had 1 recurrence, 59.1% had a second recurrence and of those who had 2 recurrences, 58.4% had ≥3 recurrences. Incident psychiatric conditions occurred in 11.3%-18.2% of each rCDI cohort; 6.0% of patients with rCDI underwent subtotal colectomy, and 1.1% of patients underwent diverting loop ileostomy. After each CDI episode, ∼1 in 5 patients had a documented sepsis event. Over the 12-month follow-up, 30% of patients experienced sepsis, and sepsis occurred in 27.0% of the cohort with no rCDI, compared to 35.5% of patients in the rCDI cohorts. Conclusions: Elderly patients with CDI and rCDI experienced a significant clinical burden and complications.

Mortality, healthcare resource utilization, and cost among Medicare beneficiaries with Clostridioides difficile infection with and without sepsis.

Objective: To describe mortality, healthcare resource utilization (HRU), and costs among Medicare beneficiaries with primary Clostridioides difficile infection (pCDI) or recurrent CDI (rCDI), with and without sepsis. Methods: We conducted a retrospective observational study of 100% Medicare Fee-for-Service claims from adults aged ⩾ 65 years with ⩾1 CDI episode between 1 January 2009 and 31 December 2017. Patients were continuously enrolled in Medicare Parts A/B/D 12 months before and up to 12 months after pCDI. ICD-9/10 codes defined CDI using ⩾1 inpatient claim, or ⩾1 outpatient claim plus ⩾1 claim for CDI treatment. The pCDI episode ended after 14 days without a CDI claim. rCDI episodes started within 8 weeks from the end of a previous CDI episode. ICD-9/10 codes identified all-cause sepsis over 12 month follow-up. Results: Of 497,489 CDI patients, 41.0% (N = 203,888) had sepsis; 57.7% with sepsis died versus 32.4% without sepsis. Among patients with pCDI only (N = 345,893) or ⩾1 rCDI (N = 151,596), 39.2% and 45.1% suffered sepsis, respectively. All-cause hospitalizations were frequent for all cohorts (range: 81-99%). Among patients who died, those with sepsis versus without had more-frequent intensive care unit (ICU) use (pCDI: 29% versus 15%; rCDI: 65% versus 34%), longer hospital stays (pCDI: 12 versus 10 days; rCDI: 12 versus 9 days), and higher per-patient-per-month costs (pCDI: $34,841 versus $22,753; rCDI: $42,269 versus $25,047). In both cohorts, sepsis patients who survived had higher total costs and all-cause HRU than those without sepsis. All p < 0.001 above. Conclusions: Sepsis was common among Medicare beneficiaries with CDI. CDI patients with sepsis, especially after an rCDI, experienced higher mortality, HRU, and costs compared with those without sepsis.

Mortality, Health Care Use, and Costs of Clostridioides difficile Infections in Older Adults.

OBJECTIVES: Estimate mortality, cost, and health care resource utilization for Medicare beneficiaries aged ≥65 years who suffered a primary Clostridioides difficile infection (CDI) episode only or any recurrent CDI, and understand how outcomes covary with death. DESIGN: Retrospective observational claims analysis. SETTING AND PARTICIPANTS: Patients aged ≥65 years who had an inpatient or outpatient CDI diagnosis claim to Medicare and continuous enrollment in Medicare parts A, B, and D during the 12-month pre- and post-index periods. METHODS: Using 100% Medicare Fee-for-Service claims data for 2009-2017, primary (pCDI, n = 345,893) and recurrent (rCDI: n = 151,596) CDI episodes were identified. Demographic and clinical characteristics, mortality, health care resource utilization, and costs (per patient per month) were summarized for 12 months before and up to 12 months after episode start. Regression models were estimated for hospitalization risk, hospital length of stay (LOS), and cost to adjust for comorbidities. RESULTS: CDI-associated deaths were almost 10 times higher after recurrent CDI (25.4%) than primary CDI (2.7%). Compared with survivors, decedents were older, had higher Charlson Comorbidity Index scores, and were more likely Black. Adjusting for comorbidities, during follow-up, decedents had higher hospitalization rates [pCDI: odds ratio (OR) = 1.83, P < .001; rCDI: OR = 2.58, P < .001], and recurrent CDI decedents had more intensive care unit use (OR = 2.34, P < .001) compared with survivors. Decedents also had a longer length of stay (pCDI: +3.2 days, P < .001; rCDI: +2.6 days, P < .001), and higher total cost (pCDI: +303%, P < .001; rCDI: +297%, P < .001). CONCLUSIONS AND IMPLICATIONS: CDI is an important contributing diagnosis to all-cause mortality, particularly for recurrences. Prior to death, older Medicare beneficiaries who experienced CDI received longer, more intensive, and more costly care compared with survivors. Clinicians should be particularly attentive to prevention, identification, and appropriate treatment of CDI in older adults. Better treatments to reduce primary C difficile infection and recurrences in this vulnerable population can lower both mortality and economic burden.

Safety and efficacy of sodium picosulfate, magnesium oxide, and citric acid bowel preparation in patients with baseline renal impairment or diabetes: subanalysis of a randomized, controlled trial.

BACKGROUND: Selecting a bowel preparation for patients with renal impairment or diabetes requires special consideration. We aimed to describe the effect of baseline renal impairment or diabetes on the safety, efficacy, and tolerability of low-volume sodium picosulfate, magnesium oxide, and citric acid (SPMC) ready-to-drink oral solution bowel preparation. METHODS: A post hoc secondary analysis was performed from a randomized, assessor-blinded study of SPMC oral solution bowel preparation in participants with mild or moderate baseline renal impairment or diabetes. Primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of ascending colon cleansing from the Boston Bowel Preparation Scale (BBPS), and selected results from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs), adenoma detection, and laboratory evaluations. RESULTS: Similar overall colon cleansing was demonstrated in the subgroups, with >85% of participants in any subgroup rated as responders by the AS, and >92% of participant responders by the BBPS. Most participants reported a tolerable bowel preparation, regardless of baseline renal impairment or diabetes history. Safety of SPMC oral solution was similar between all subgroups and the overall cohort. For the mild renal impairment, moderate renal impairment, and diabetes subgroups, respectively, commonly reported, drug-related AEs were nausea (2.6%, 5.3%, 1.4%) and headache (2.2%, 2.6%, 4.3%). CONCLUSIONS: Ready-to-drink SPMC oral solution demonstrated efficacious colon cleansing in patients with baseline mild/moderate renal impairment or diabetes, with a tolerable bowel preparation reported by most. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03017235.

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.

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation in overweight and obese adults: subanalysis by body mass index from a phase III, assessor-blinded study.

BACKGROUND: We performed a post hoc secondary analysis for the effect of body mass index (BMI) on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation. METHODS: A phase III, randomized, assessor-blinded, multicenter, noninferiority study was conducted comparing split-dose, low-volume SPMC oral solution with a powder formulation for oral solution. A post hoc secondary analysis assessed efficacy, safety, and tolerability of SPMC oral solution stratified by BMI. BMI was classified by Centers for Disease Control and Prevention definitions (underweight and normal weight: BMI < 25 kg/m2; overweight: BMI 25-29.9 kg/m2; class I obesity: BMI 30-34.9 kg/m2; class II obesity: BMI 35-39.9 kg/m2; class III/severe obesity: BMI ⩾40 kg/m2). Prespecified primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation 'easy' or 'acceptable' to ingest, and the majority (>58%) rated SPMC oral solution as 'better' than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%). CONCLUSIONS: Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups. CLINICALTRIALSGOV REGISTRATION: NCT03017235.

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation: subanalysis by age from a phase III, assessor-blinded study.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) increase with age and, therefore, it is recommended that adults undergo regular CRC screening, ideally by colonoscopy, with some new guidelines recommending screening begin at 45 years. Effective bowel preparation is a critical step to a successful colonoscopy. Of concern is that older adults may have poorer quality of bowel preparation or reduced tolerability for the bowel preparation. Here, we performed a post hoc secondary analysis for the effect of age on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation. METHODS: A phase III, randomized, assessor-blinded, multicenter, non-inferiority study was conducted comparing split-dose, low-volume SPMC oral solution with split-dose, low-volume sodium picosulfate, magnesium oxide, and citric acid powder for oral solution. A post hoc secondary analysis was performed to assess efficacy, safety, and tolerability of SPMC oral solution by age group (<50 years, 50-64 years, ⩾65 years). The prespecified primary efficacy endpoint ('responders') was the proportion of participants with 'excellent' or 'good' ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations. RESULTS: Within age groups, at least 83.9% of participants were responders by the AS, and at least 91.1% of participants were responders by the BBPS in the right colon. On both scales, responder rates were highest in the youngest age group and decreased with increasing age. Greater than 88% of participants in any age group found the preparation 'easy' or 'acceptable' to ingest, with rates of 'easy' being highest in the oldest age group. No new safety signals were seen in any age group. The most commonly reported drug-related, treatment-emergent AEs were, by ascending age group, nausea (7.0%, 3.2%, 0.8%), headache (4.2%, 2.8%, 1.6%) and vomiting (2.8%, 1.2%, 0.8%). CONCLUSION: Ready-to-drink SPMC oral solution showed good efficacy of overall colon cleansing and tolerability in adults across different age groups, including those ⩾65 years.ClinicalTrials.gov identifier: NCT03017235.

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.

Real-world comparison of the effectiveness and safety of different bowel preparation agents.

BACKGROUND AND AIMS: Proper bowel cleansing is necessary prior to colonoscopy, but poor tolerability to bowel preparation agents may increase the odds of poor cleansing and incomplete screenings. The aim of this study was to evaluate the real-world effectiveness and safety of bowel preparation agents. METHODS: Claims data were extracted for individuals who had a screening colonoscopy from July 1, 2012, to June 30, 2015, were ≥18 years of age, and who could be observed ≥6 months before and ≥3 months after the screening. Data were stratified by agent class, including over-the-counter (OTC), low-volume (LV), and high-volume (HV) agents. Rates of incomplete screenings, repeat screenings, and hospitalizations were reported. Multivariate logistic regression was conducted to compare outcomes for sodium picosulfate, magnesium oxide, and citric acid (P/MC) vs other agents. RESULTS: Of 2.8 million individuals, 71.5% were average risk and 28.5% were high risk for colorectal cancer. Rates of use were 2.8% for P/MC, 30.1% for other LV agents, 9.4% for HV agents, and 56.6% for OTC agents. All individuals who used P/MC had significantly lower odds of incomplete screenings compared to those who used other LV agents or HV agents (P<0.05). In average-risk patients, rates of 30- and 90-day repeat screenings were highest for the P/MC group (16.7% and 23.0%, respectively) compared to other agents. Across all patient analysis groups, the rates of hospitalizations for hyponatremia or dehydration were much higher for those who used an OTC bowel preparation agent compared to those who used LV or HV agents, or P/MC. CONCLUSION: P/MC was associated with lower rates of incomplete colonoscopy and higher rates of repeat screenings, suggesting it was better tolerated than other agents. OTC agents were associated with higher rates of hospitalizations.

Comparison of claims data on hospitalization rates and repeat procedures in patients receiving a bowel preparation prior to colonoscopy.

OBJECTIVES: To evaluate outcomes of colorectal screening using sodium picosulfate and magnesium citrate compared with other prescription bowel-preparation agents. Primary endpoints were rates of procedure-associated hospitalizations, diagnosis at hospitalization, and rates of early repeat screenings. METHODS: This retrospective cohort study identified patients using the Truven Health Analytics MarketScan databases, which contain fully adjudicated, de-identified, medical- and prescription-drug claims, as well as demographic and enrollment information for individuals with commercial, Medicaid, and Medicare supplemental insurance coverage. Patients who had a colonoscopy or sigmoidoscopy over a 3-year period were identified using International Classification of Diseases Clinical Modification procedure codes, recorded on claims from physicians and facilities. First, screening colonoscopy was identified for each patient, and the study was limited to those patients who could be observed for ≥6 months before and 3 months after the screening procedure. Total number of hospitalizations and rates of early repeat screenings were evaluated for all patients who received sodium picosulfate and magnesium citrate and compared with those who received other bowel-preparation agents. Individual prescription medications that could affect the outcome of the cleansing agent were identified; further evaluations were made to establish whether patients had comorbid conditions, such as chronic kidney disease, cardiovascular disease, or psychiatric illness. Statistical methods included descriptive statistics, two-tailed t-tests, and multivariate logistic regression. RESULTS: A total of 566,628 procedures were identified in the MarketScan databases and included in the study. Sodium picosulfate and magnesium citrate performed well in terms of safety outcomes, with no hospitalizations due to diagnosis of hyponatremia, dehydration, or other fluid disorders in the 10 days after procedure. Early repeat rates among sodium picosulfate and magnesium citrate patients were comparable with rates observed for all other cleansing agents. CONCLUSION: Outcomes of colorectal screening using sodium picosulfate and magnesium citrate were not significantly different compared with other prescription bowel-preparation agents.

The potential role of follicle-stimulating hormone in the cardiovascular, metabolic, skeletal, and cognitive effects associated with androgen deprivation therapy.

PURPOSE: To explore how follicle-stimulating hormone (FSH) may contribute to cardiovascular, metabolic, skeletal, and cognitive events in men treated for prostate cancer, with various forms of androgen deprivation therapy (ADT). MATERIALS AND METHODS: A colloquium of prostate cancer experts was convened in May 2015, to discuss the role of FSH in the development of unwanted effects associated with ADT. Subsequently, a literature review (Medline, PubMed, and relevant congress abstract databases) was performed to further explore and evaluate the collected evidence. RESULTS: It has become evident that, in the setting of ADT, FSH can promote the development of atherosclerotic plaque formation, metabolic syndrome, and insulin resistance. Data also suggest that FSH is an important mediator of bone remodeling, particularly bone resorption, and thereby increases the risk for bone fracture. Additional evidence implicates a role for FSH in bone metastasis as well. The influence of FSH on ADT-induced cognitive deficits awaits further elucidation; however, the possibility that FSH may be involved therein cannot be ruled out. CONCLUSIONS: The widespread molecular and physiological consequences of FSH system activation in normal and pathological conditions are becoming better understood. Progress in this area has been achieved by the development of additional investigative and clinical measures to better evaluate specific adverse effects. More research is needed on FSH function in the development of cancer as well as its association with cardiovascular, metabolic, musculoskeletal, and cognitive effects in ADT.

Validation of a Patient Satisfaction Scale in Patients Undergoing Bowel Preparation Prior to Colonoscopy.

BACKGROUND: Colonoscopy is the most widely used test to screen for colorectal cancer but its use may be hindered by patients' inability to complete the bowel preparation. Patient-reported satisfaction with bowel-cleansing preparations has received little attention. We assessed the reliability and validity of a patient satisfaction survey used in two large, multicenter, randomized, assessor-blinded colonoscopy trials. METHODS: Datasets from two pivotal trials were combined. Patients in both trials included men and women aged 18-80 years who were scheduled for an elective outpatient colonoscopy. Questions relevant to satisfaction with bowel preparation prior to colonoscopy were identified from the literature and incorporated into a 7-item survey administered to patients on the day of colonoscopy. Domain 1 of the satisfaction measure assessed difficulty using bowel-cleansing preparations, ability to consume preparations, acceptability of taste, and overall experience; questions regarding acceptance or refusal of future use of the same bowel preparation were asked in Domain 2. Responses from each item of Domain 1 were transformed on a scale ranging from 0 to 100 and summed as total satisfaction scores. Cronbach's alpha was used to measure reliability; validity was assessed by evaluating relationship between total satisfaction (Domain 1) and willingness to use preparation in the future (Domain 2). RESULTS: Mean age of the 1211 trial participants was 56: 61 % female, 89.5 % Caucasian. Domain 1 had a Cronbach's alpha of 0.79, with higher satisfaction predicting higher future acceptability (p < 0.0001). CONCLUSION: The patient-reported satisfaction measure of bowel-cleansing preparations possesses good validity and reliability.

Serum magnesium concentrations in patients receiving sodium picosulfate and magnesium citrate bowel preparation: an assessment of renal function and electrocardiographic conduction.

BACKGROUND: We performed a post hoc analysis of two clinical trials to assess whether sodium picosulfate and magnesium (Mg(2+)) citrate (Prepopik(®) [P/MC]), a dual-action bowel preparation for colonoscopy, has an impact on serum Mg(2+) levels and cardiac electrophysiology. Although rare, hypermagnesemia has been reported in patients consuming Mg(2+)-containing cathartics, especially patients who are elderly and have renal impairment. METHODS: Data were analyzed from two prospective, Phase III, randomized, assessor-blinded, active-control, multicenter, pivotal studies that investigated split-dose/day-before P/MC. Serum Mg(2+) and creatinine clearance (CrCl) were measured at screening, on the day of colonoscopy, and 24-48 hours, 7 days, and 4 weeks after colonoscopy; electrocardiograms also were obtained at these time points. RESULTS: In total, 304 patients received split-dose P/MC and 294 patients received day-before P/MC. Only 10% of the patients had serum Mg(2+) above the upper limit of normal (1.05 mmol/L) on the day of colonoscopy. There was a slight inverse correlation between CrCl and Mg(2+) levels on the day of colonoscopy; however, even at the lowest CrCl, serum Mg(2+) remained below clinically significant levels of 2.0 mmol/L. Increases in serum Mg(2+) were transient, with levels returning to baseline within 24-48 hours, regardless of renal function. No patients with elevated Mg(2+) experienced a corrected QT (QTc) interval >500 milliseconds or a QTc interval increase of ≥60 milliseconds from baseline. P/MC had no impact on PR or QRS interval. CONCLUSION: P/MC produces little impact on serum Mg(2+) levels with no clinically significant effect on cardiac conduction in patients, including those with mild-to-moderate renal impairment.