Purpose
The aim of this study was to generate evidence supporting the development and content validity of a new PRO instrument, the Small Intestinal Bacterial Overgrowth (SIBO) Symptom Measure (SSM) ...daily diary. The SSM assesses symptom severity in SIBO patients, with the ultimate goal of providing a fit for purpose PRO for endpoint measurement.
Methods
Qualitative research included 35 SIBO patients in three study stages, using a hybrid concept elicitation (CE)/cognitive interview (CI) method with US patients, ≥ 18 years. Stage 1 included a literature review, clinician interviews, and initial CE interviews with SIBO patients to identify symptoms important to patients for inclusion in the SSM. Stage 2 included hybrid CE/CI to learn more about patients’ SIBO experience and test the draft SSM. Finally, stage 3 used CIs to refine the instrument and test its content validity.
Results
In stage 1 (
n
= 8), 15 relevant concepts were identified, with items drafted based on the literature review/clinician interviews and elicitation work. Within stage 2 (
n
= 15), the SSM was refined to include 11 items; with wording revised for three items. Stage 3 (
n
= 12) confirmed the comprehensiveness of the SSM, as well as appropriateness of the item wording, recall period, and response scale. The resulting 11-item SSM assesses the severity of bloating, abdominal distention, abdominal discomfort, abdominal pain, flatulence, physical tiredness, nausea, diarrhea, constipation, appetite loss, and belching.
Conclusions
This study provides evidence supporting the content validity of the new PRO. Comprehensive patient input ensures that the SSM is a well-defined measure of SIBO, ready for psychometric validation studies.
Oral oncolytic therapies have improved survival in hematologic cancers, such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and multiple myeloma (MM), which are now being ...managed like chronic conditions. However, compared with other cancers, there is a lack of studies assessing adherence, health care resource utilization, and costs in patients with these cancers.
To assess factors associated with adherence to oral oncolytic therapies, health care utilization, and costs in patients with CLL/SLL or MM.
A retrospective database study was conducted using the IBM MarketScan Commercial Claims and Medicare Supplement databases. Adults (aged ≥ 18 years) diagnosed with and prescribed an oral oncolytic for CLL/SLL (ibrutinib or idelalisib) or MM (thalidomide, lenalidomide, or pomalidomide) between 2013 and 2016 and with continuous eligibility 6 months before and 12 months after oral oncolytic initiation were identified. Adherence to oral oncolytics was measured using the proportion of days covered (PDC) metric. Multiple linear regression and multivariable logistic regression were used to identify adherence predictors. Count models assessed the relationship between adherence and resource utilization, and generalized linear models assessed the relationship between adherence and health care costs.
A total of 701 and 2,385 patients were identified with CLL/SLL or MM, respectively. Mean PDC (SD) for CLL/SLL and MM patients was 75.3 (22.5) and 57.6 (26.5), respectively. For CLL/SLL patients, those aged ≥ 65 years (beta B = -4.00) had lower medication use. Among MM patients, multiple predictors of higher medication use emerged: aged ≥ 65 years (B = 3.44), higher than average outpatient resource utilization (B = 3.53), insurance plan other than preferred provider organization (PPO; B = -2.58), previous cancer therapy (B = -2.81), higher number of concurrent unique therapeutic classes (B = -0.35), and higher comorbidity burden (B = -2.55). Patients with CLL/SLL and enrolled in plans other than a PPO were more likely to be adherent (OR = 1.41, 95% CI = 1.01-1.98), whereas patients who were aged ≥ 65 years, were residents of the southern United States, and had visited the emergency department in the baseline period were less likely to be adherent. For MM patients, those aged ≥ 65 years (OR = 1.68, 95% CI = 1.38-2.04) and with higher than average outpatient services utilization (OR = 1.24, 95% CI = 1.01-1.52) were more likely to be adherent, whereas those enrolled in plans other than a PPO, previously treated with cancer therapy, and with higher comorbidity burden were less likely to be adherent. In both cohorts, adherent patients had significantly lower odds of health care utilization and incurred lower medical costs, but higher prescription costs, following oncolytic initiation; however, total costs were not significantly lower in those adherent.
Factors were identified that influenced adherence at the patient, treatment, and health system levels. These factors can be used to identify patients requiring interventions for improving medication-taking behavior and associated health care burden.
This study received no outside funding. Dashputre was recently employed by Novartis; K. Gatwood has received speaker fees from Jazz Pharmaceuticals; and J. Gatwood has received research funding from Merck & Co. and GlaxoSmithKline, unrelated to this study..
Abstract
Background
Constipation is highly prevalent in patients with chronic kidney disease (CKD), particularly among those with end-stage renal disease (ESRD), partly due to their dietary ...restrictions, comorbidities and medications. Laxatives are typically used for constipation management; however, little is known about laxative use and its associated factors in patients with advanced CKD transitioning to ESRD.
Methods
In a retrospective cohort of 102 477 US veterans transitioning to dialysis between October 2007 and March 2015, we examined the proportion of patients who filled a prescription for any type of laxative within each 6-month period over 36 months pre- and post-transition to ESRD. Factors associated with laxative use during the last 1-year pre-ESRD period were identified by multivariable logistic regression.
Results
The proportion of patients prescribed laxatives increased as patients progressed to ESRD, peaking at 37.1% in the 6 months immediately following ESRD transition, then remaining fairly stable throughout the post-ESRD transition period. Among laxative users, stool softeners were the most commonly prescribed (∼30%), followed by hyperosmotics (∼20%), stimulants (∼10%), bulk formers (∼3%), chloride channel activator (<1%) and several combinations of these. The use of anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics were among the factors independently associated with pre-ESRD laxative use.
Conclusion
The use of laxatives increased considerably as patients neared transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD.
Patients with advanced CKD experience increased intestinal potassium excretion. This compensatory mechanism may be enhanced by laxative use; however, little is known about the association of laxative ...use with risk of dyskalemia in advanced CKD.
Our study population encompassed 36,116 United States veterans transitioning to ESKD from 2007 to 2015 with greater than or equal to one plasma potassium measurement during the last 1-year period before ESKD transition. Using generalized estimating equations with adjustment for potential confounders, we examined the association of time-varying laxative use with risk of dyskalemia (
., hypokalemia potassium <3.5 mEq/L or hyperkalemia >5.5 mEq/L) versus normokalemia (3.5-5.5 mEq/L) over the 1-year pre-ESKD period. To avoid potential overestimation of dyskalemia risk, potassium measurements within 7 days following a dyskalemia event were disregarded in the analyses.
Over the last 1-year pre-ESKD period, there were 319,219 repeated potassium measurements in the cohort. Of these, 12,787 (4.0%) represented hypokalemia, and 15,842 (5.0%) represented hyperkalemia; the time-averaged potassium measurement was 4.5 mEq/L. After multivariable adjustment, time-varying laxative use (compared with nonuse) was significantly associated with lower risk of hyperkalemia (adjusted odds ratio aOR, 0.79; 95% confidence interval 95% CI, 0.76 to 0.84) but was not associated with risk of hypokalemia (aOR, 1.01; 95% CI, 0.95 to 1.07). The results were robust to several sensitivity analyses.
Laxative use was independently associated with lower risk of hyperkalemia during the last 1-year pre-ESKD period. Our findings support a putative role of constipation in potassium disarrays and also support (with a careful consideration for the risk-benefit profiles) the therapeutic potential of laxatives in hyperkalemia management in advanced CKD.
Patiromer is a potassium binder approved for the long-term management of hyperkalemia. Although patiromer use among patients with advanced chronic kidney disease (CKD) has been shown to reduce the ...discontinuation of renin-angiotensin-aldosterone system inhibition therapy, it remains unclear whether patiromer can improve clinical outcomes. The aim of this study was to examine the association of long-term patiromer use with clinical outcomes among hyperkalemic patients with CKD.
This was a longitudinal observational study.
We evaluated a national cohort of 854,217 US Veterans who had at least 1 serum potassium measurement of ≥5.1 mEq/L and were treated at US Department of Veterans Affairs health care facilities between January 2016 and September 2019.
The exposure was long-term patiromer use.
The outcomes were as follows: (1) composite endpoint of kidney failure with replacement therapy (KFRT) or all-cause death and (2) all-cause death including the post-KFRT period.
Cox proportional Fine-Gray subdistribution hazard models were used in a propensity-matched cohort.
Among 2,004 patients who ever used patiromer during the study period (0.2% of the cohort), 666 met the criteria for long-term patiromer use. We matched 308 long-term patiromer users to 308 nonusers based on propensity scores. The median estimated glomerular filtration rate was 23.5 mL/min/1.73m
, and the median potassium level was 5.2 mEq/L. Approximately 45% were on renin-angiotensin system inhibitor(s) at baseline. During follow-up, 93 patients developed KFRT, and 134 patients died. Long-term patiromer users, when compared to nonusers, experienced a 26% lower risk of the composite outcome (HR, 0.74; 95% CI, 0.53-1.01;
= 0.06) and a 41% lower risk of all-cause mortality (HR, 0.59; 95% CI, 0.41-0.84;
= 0.003).
The study cohort included mostly male veterans with relatively short follow-up periods.
Long-term patiromer use was associated with a lower risk of all-cause mortality among patients with CKD and hyperkalemia. Long-term potassium binder use for hyperkalemia may improve clinical outcomes in CKD.
Hyperkalemia is a common complication of chronic kidney disease (CKD) and can result in the discontinuation of renin-angiotensin-aldosterone system inhibition therapy, a cornerstone of CKD management. Patiromer is a new potassium binder approved for the long-term management of hyperkalemia, but it remains unclear whether patiromer can improve clinical outcomes. We examined a cohort of US Veterans with hyperkalemia between January 2016 and September 2019 and found that patiromer use was uncommon for treating hyperkalemia during this study period. We then matched 308 long-term patiromer users and 308 nonusers based on propensity scores. Long-term patiromer users, when compared to nonusers, experienced a 26% lower risk of the composite outcome and a 41% lower risk of all-cause mortality. These findings indicate that long-term potassium binder use for hyperkalemia may improve clinical outcomes in CKD.
Introduction
Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, ...and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA.
Methods
Adult patients (18–64 years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics
®
Plus database (10/01/2015–12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30 consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences.
Results
There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1 years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30 days (76.2% vs. 66.7%), ≥ 60 days (67.0% vs. 47.0%), ≥ 90 days (61.0% vs. 38.7%), ≥ 180 days (51.7% vs. 31.0%), and ≥ 240 days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30 days, mean TFI durations were 8.3 and 6.0 months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437;
p
= 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250;
p
< 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1 million per year or $0.18 per-member-per-month.
Conclusions
This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.
Purpose
Oral oncolytics have improved survival in hematological cancers like chronic myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and multiple myeloma; however, it is ...unclear of the extent to which initiating these treatments might impact adherence to oral therapies for pre-existing comorbid chronic conditions.
Methods
Adults diagnosed with and prescribed oral oncolytics for chronic myeloid leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, or multiple myeloma between 2013 and 2016 and with continuous eligibility six months before and after oral oncolytic initiation were identified from the Truven Health MarketScan databases. Among those identified, patients with pre-existing diabetes, hypertension, and/or hyperlipidemia with ≥1 fill for oral comorbid therapies were selected. Adherence to oral oncolytics and comorbid therapies was measured using the proportion of days covered metric. Wilcoxon signed-rank tests assessed changes in adherence for comorbid therapies after initiation of an oral oncolytic. Unadjusted difference-in-difference models assessed the impact of adherence to oral oncolytics on changes in adherence to comorbid therapies.
Results
Significant reductions in adherence after oncolytic initiation were observed across the comorbid therapies and were highest for patients taking lipid-lower agents (10.7–15.6%). Unadjusted difference-in-difference models revealed consistent and significantly lower reductions in adherence for those taking antihypertensives (chronic myeloid leukemia: p = 0.03; chronic lymphocytic leukemia/small lymphocytic lymphoma: p = 0.007; multiple myeloma: p = 0.09) and adherent to oral oncolytics.
Conclusion
Initiation of oral oncolytics may negatively impact adherence to oral therapies for chronic comorbid conditions, necessitating the need for medication management strategies to help patients adhere to their entire medication regimen.
AIMTo assess the impact of rifaximin (± lactulose) use following discharge of an initial overt hepatic encephalopathy (OHE) hospitalization on OHE rehospitalizations and healthcare costs in a ...real-world setting.METHODSAdults (18-64 years) with an OHE hospitalization were identified from MarketScan® Commercial claims (Q4'15-Q2'20), classified into two mutually exclusive treatment cohorts (i.e. rifaximin and no rifaximin treatment), and further stratified into four subgroups based on decreasing quality of care (QoC; i.e. Type 1 - rifaximin without delay post-discharge; Type 2 - rifaximin with delay post-discharge; Type 3 - lactulose only post-discharge; Type 4 - no rifaximin/lactulose treatment post-discharge). The impact of rifaximin use on 30-day and annualized OHE hospitalizations and healthcare costs were assessed between cohorts and by the QoC subgroup.RESULTSCharacteristics were similar between the rifaximin (N = 1,452; Type 1: 1,138, Type 2: 314) and no rifaximin (N = 560; Type 3:337, Type 4: 223) treatment cohorts. The 30-day risk of OHE rehospitalization was lower for the rifaximin vs. no rifaximin treatment cohort (odds ratio 0.56, p < .01) and increased with decreasing QoC. The annual rate of OHE hospitalizations was 59% lower for the rifaximin treatment cohort (incidence rate ratio 0.41, p < .01) and increased with decreasing QoC. Compared to the no rifaximin treatment cohort, the rifaximin treatment cohort had higher pharmacy costs, lower medical costs, and no difference in total healthcare costs.LIMITATIONSThis was a claims-based study subject to common data limitations such as billing inaccuracies or omissions in coded claims. Total healthcare costs were reported from a payer's perspective, which do not capture indirect costs associated with patient burden.CONCLUSIONSInitiation of rifaximin after an OHE hospitalization was associated with reduced OHE hospitalizations both in the 30-days following and annually. Further, reduced medical costs offset increased pharmacy costs, and no annual cost differences were observed between cohorts.
Objectives
The prevalence and burdens of obesity‐associated chronic conditions (OCC) are rising nationwide, particularly in health professional shortage areas (HPSA). This study examined the impact ...of access to primary care on health care utilization for vulnerable populations with OCC in the South.
Methods
Adult patients with obesity (BMI ≥ 30 kg/m2), greater than or equal to one additional OCC, and self‐reported primary care access data were retrospectively identified from hospital and emergency department (ED) electronic medical records of a major health care system in the South. Multivariable logistic regression assessed factors associated with self‐reported access to primary care. Multivariable zero‐inflated negative binomial models assessed effect of HPSA residence on relationships between self‐reported access to primary care and health care utilization.
Results
A total of 29 674 patients were identified. Hypertension (76.1%), type 2 diabetes mellitus (34.1%), and hyperlipidemia (32.9%) were the most prevalent OCC. Males (odds ratio OR: 0.43; 95% confidence interval CI, 0.40‐0.47), unmarried (OR: 0.69; 95% CI, 0.63‐0.76), and uninsured (OR: 0.29; 95% CI, 0.27‐0.32) had lower odds of access to primary care. For patients living in HPSA (vs non‐HPSA), access to primary care was associated with higher incidence of overall ED use (relative risk RR: 1.38; 95% CI, 1.19‐1.61) and lower incidence of potentially preventable hospital use (RR: 0.59; 95% CI, 0.38‐0.92).
Conclusion
Paradoxically, access to primary care may increase ED use while reducing potentially preventable hospital utilization for patients with OCC in HPSA. Increasing access to primary care alone, without strengthening its capacity to serve the needs of vulnerable patients, may be insufficient to reduce hospital utilization.
Patients with end-stage renal disease (ESRD) display phenotypic features of premature biological aging, characterized by disproportionately high morbidity and mortality at a younger age. Nuclear ...factor erythroid 2-related factor 2 (Nrf2) activity, a master regulator of antioxidative responses, declines with age and is implicated in the pathogenesis of age-related disorders; however, little is known about the association between Nrf2 and premature biological aging in ESRD patients. In a cross-sectional pilot cohort of 34 ESRD patients receiving maintenance hemodialysis, we measured the expression of Nrf2 and cyclin-dependent kinase inhibitor 2A (CDKN2A, or p16
, a biomarker of biological aging) genes in whole blood and examined the association of Nrf2 with CDKN2A expression, using Spearman's rank correlation and multivariable linear regression models with adjustment for potential confounders. There was a significant negative correlation between Nrf2 and CDKN2A expression (rho=-0.51,
=0.002); while no significant correlation was found between Nrf2 expression and chronological age (rho=-0.02,
=0.91). After multivariable adjustment, Nrf2 expression remained significantly and negatively associated with CDKN2A expression (
coefficient=-1.51,
=0.01), independent of chronological age, gender, race, and diabetes status. These findings suggest a potential contribution of Nrf2 dysfunction to the development of premature biological aging and its related morbidities in ESRD patients.
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