Impact of Recent Acute Kidney Injury on Creatinine Clearance Estimation in Critically Ill Patients Undergoing Cardiac Surgery.

Acute kidney injury (AKI), often present in critically ill patients and patients with cardiac dysfunction, may alter estimates of renal function. The impact of recent AKI on the accuracy of the Cockcroft-Gault creatinine clearance equation (CG-CrCl) before cardiac surgery is unknown. This single-center, retrospective study included patients who underwent cardiac surgery from 1 January 2006 through 30 June 2012 and whose 24-hour urine creatinine clearance (24hr-CrCl) was measured in the intensive care unit before surgery. We evaluated CG-CrCl accuracy by calculating absolute differences between 24hr-CrCl and CG-CrCl estimates. Clinical impact was signified by discrepancies in United States Food and Drug Administration (FDA) renal impairment stage indicated by 24hr-CrCl versus CG-CrCl estimates. Acute kidney injury was evaluated by using Kidney Disease: Improving Global Outcomes criteria. Of 161 patients, 93 (58%) had recent AKI: stage 1, 31 (33%); stage 2, 39 (42%); and stage 3, 23 (25%). In mL/min, the CG-CrCl overestimated 24hr-CrCl (absolute difference: total, -10 ± 25; no AKI, -7 ± 26; stage 1, -8 ± 17; stage 2, -16 ± 28; and stage 3, -10 ± 26; P=0.29). Renal impairment stages assigned by CG-CrCl did not match 24hr-CrCl in 70 (43%) of the 161 patients, especially those with recent AKI: no AKI, 24/68 (35%); stage 1, 13/31 (42%); stage 2, 23/39 (59%); and stage 3, 10/23 (43%). The CG-CrCl consistently overestimated 24hr-CrCl in critically ill patients before cardiac surgery. Clinicians should use the CG-CrCl cautiously when estimating renal function and medication dosages in this population.

FACTORS ASSOCIATED WITH SWITCHING FROM INJECTABLE TO ORAL DISEASE MODIFYING AGENTS AMONG PATIENTS WITH MULTIPLE SCLEROSIS.

BACKGROUND: Since the introduction of oral disease-modifying agents (DMA) in 2010, the treatment options for multiple sclerosis (MS) have changed significantly. There is limited information regarding the factors associated with switching to oral DMA among prevalent injectable DMA users. OBJECTIVE: This study evaluated the factors associated with switching to oral DMAs among prevalent injectable DMA users with MS. METHODS: A retrospective observational cohort study using the TriNetX electronic medical records (EMR) data was conducted among patients with MS. The study included prevalent injectable DMA users with at least two injectable DMA (interferon beta-1a, interferon beta-1b, peginterferon beta-1a, or glatiramer acetate) prescription records within 6 months between September 2010 and May 2018. The second injectable DMA prescription date was considered as the index date. Switching was defined as any oral DMA prescription record (fingolimod, dimethyl fumarate, or teriflunomide) within 12 months after the index date. Patients with any infusion DMA prescription after the first injectable DMA prescription, and those less than 18 years of age were excluded from the study. The Andersen Behavioral Model was used as the conceptual framework to identify predisposing, enabling, and need factors measured during the 1-year baseline period before the index date. A multivariable logistic regression model was used to examine the predisposing (age, sex, race, and ethnicity), enabling (time-period), and need factors (comorbidities, MS symptoms, MS-related medication, and healthcare utilization) associated with switching from injectable to oral DMAs. RESULTS: Among 2,943 prevalent injectable users included in this study, 8.09% (n=238) patients switched to oral DMAs. Patients who switched to oral DMAs were primarily younger adults aged 18-44 years (64.29%), females (82.77%), had sensory and visual symptoms, and had corticosteroid utilization during the one-year look-back period compared to non-switchers. Results from multivariable logistic regression model revealed that middle-aged adults (45-64 years, adjusted odds ratio [aOR]: 0.43, 95% Confidence Interval [CI]: 0.32-0.58), old adults (≥65 years, aOR: 0.30, 95% CI: 0.13-0.66) and men (aOR: 0.67, 95% CI: 0.47-0.96) were associated with decreased odds of switching to oral DMAs. Presence of MS-related sensory symptoms (aOR: 1.52, 95% CI: 1.07-2.16), visual symptoms (aOR: 1.59, 95% CI: 1.10-2.31), and corticosteroids usage (aOR: 1.44, 95% CI: 1.04-1.98) were associated with increased odds of switching to oral DMAs. CONCLUSION: The study found that about one in twelve prevalent injectable DMA users switched to oral DMA. Both demographic and clinical factors were associated with switching to oral DMAs. Further research is needed to evaluate the outcomes of switching to inform treatment decisions for MS management.

Prescribing of disease modifying agents in older adults with multiple sclerosis.

BACKGROUND: The use of disease-modifying agents (DMAs) to treat Multiple Sclerosis (MS) in older adults is debated as the disease activity decreases with aging. However, limited data exist regarding prescribing patterns of DMAs among older adults with MS. OBJECTIVE: To examine prescribing patterns of DMAs and the factors associated with DMA prescribing practices among older adults with MS using electronic medical records (EMR) data. METHODS: A retrospective longitudinal cohort study was conducted using the TriNetX, a federated EMR network from the US, data from 2016 to 2019. The study included older adults (≥60 years) with MS diagnosis and at least one prescription record during the study period. Patients with DMA prescriptions were identified and further classified into injectable, oral, or infusion users based on their last DMA prescription. A multivariable logistic regression model was used to evaluate the factors associated with prescribing of DMAs. A multinomial logistic regression model was also used to determine the factors associated with prescribing a particular dosage form of DMA. RESULTS: The study cohort consisted of 12,922 older adults with MS, with 2,455 (18.99%) receiving DMA prescriptions. The commonly prescribed DMAs were injectables (10.46%), followed by orals (6.06%) and infusions (2.40%). Multivariable logistic regression revealed that older adults between 60- to 64 years (Adjusted Odds Ratio [aOR]= 2.38) and 65-69 years (aOR=1.60) had higher odds of receiving DMA compared to older adults of 70 years and above. African Americans (aOR=1.71) had higher odds of receiving DMA prescriptions compared to Caucasians. The presence of symptoms (pain, fatigue, speech, walking difficulty) and use of symptomatic medication (anti-fatigue medication, bladder dysfunction medication, antispasmodics, antidepressants, and relapse medication) increased the odds of being prescribed DMAs. Multinomial logistic regression found that patients 60-64 years of age had higher odds of being prescribed infusion (aOR, 95% Confidence Interval [CI] =2.06, 1.35-3.15) and oral (65-69 years: aOR=1.60, 1.24-2.07) over injectable DMAs compared to the older adults aged 70 years and above.Older males (aOR=1.68, 95% CI: 1.23-2.30) were associated with increased odds of being prescribed infusion DMA over injectable DMA compared to females. The presence of comorbidities such as coagulopathy and peripheral vascular disorders decreased the odds of being prescribed oral DMA over injectable DMA. Patients with cerebellar symptoms had an increased likelihood of being prescribed with an infusion DMA over injectable DMA. Patients using drugs for treating relapses had higher odds of being prescribed an infusion DMA over an injectable DMA. In terms of healthcare utilization, older adults with outpatient visits had higher odds of being prescribed an infusion DMA over an injectable DMA, while older adults with inpatient visits had lower odds of being prescribed an infusion DMA over an injectable DMA. CONCLUSION: Nearly one in five older adults with MS are prescribed DMAs, with a majority receiving injectable DMAs. Several demographic and clinical factors were associated with DMA prescribing . This study fills the data gap regarding the utilization of DMAs in older adults with MS.

Comparative treatment effectiveness of oral fingolimod and conventional injectable disease-modifying agents in multiple sclerosis.

STUDY OBJECTIVE: To compare the effectiveness of oral fingolimod and conventional injectable disease-modifying agents (DMAs) using the composite endpoint of relapse or DMA treatment switch in patients with multiple sclerosis (MS). DESIGN: A retrospective longitudinal cohort study. DATA SOURCE: IBM MarketScan Commercial Claims and Encounters Database from 2010-2012. PATIENTS: Adults (≥18 years) with MS diagnosis (ICD-9-CM:340) who newly initiated DMAs. INTERVENTION: Oral fingolimod and conventional injectable DMAs (interferon beta and glatiramer acetate). MEASUREMENTS: Composite endpoint of time to relapse or DMA treatment switch. MAIN RESULTS: The incident study cohort consisted of 1997 MS patients who initiated oral fingolimod (15.6%) or injectable (84.4%) DMAs. The proportion of patients who had a composite endpoint (relapse/DMA treatment switch) in oral fingolimod and injectable DMA users was found to be 16.72% and 27.16%, respectively. The Cox PH regression model with stabilized IPTW revealed that fingolimod is equally effective as conventional injectable DMAs in reducing the risk of experiencing the composite endpoint of relapse or DMA switch (adjusted hazard ratio [aHR]: 0.67, 95% CI: 0.43-1.03). Additional analysis among patients who were adherent also found no significant difference in the composite endpoint (aHR: 0.70, 95% CI 0.49-1.15) between oral fingolimod and injectable DMA users. CONCLUSIONS: Oral fingolimod has similar effectiveness as conventional injectable DMAs in reducing the risk of experiencing the composite endpoint (relapse or DMA treatment switch). In addition, when assessed independently, oral fingolimod showed no difference in reducing the time to relapse or DMA treatment switch compared to injectable DMAs.

Comparative Adherence Trajectories of Oral Fingolimod and Injectable Disease Modifying Agents in Multiple Sclerosis.

BACKGROUND: Oral fingolimod is convenient to use than injectable disease modifying agents (DMAs) in patients with multiple sclerosis (MS). However, the existing literature regarding the comparative adherence trajectories between oral fingolimod and injectable DMAs is limited. OBJECTIVE: To compare the adherence trajectories between oral DMA, fingolimod, and injectable DMAs in patients with MS. METHODS: A retrospective longitudinal study was conducted using adults (≥18 years) with MS (ICD-9-CM: 340 and a DMA prescription) from the IBM MarketScan Commercial Claims and Encounters Database between 2010 and 2012. Patients were grouped into oral fingolimod or injectable DMA users based on the index DMA among patients with MS. The annual DMA adherence trajectories, based on the proportion of days covered (PDC), were examined using group-based trajectory modeling (GBTM) during the one-year follow-up period after treatment initiation. Multivariable multinomial logistic regression using stabilized inverse probability treatment weights (IPTW) was performed to assess the association between the DMA route of administration (Oral vs Injectable) and the adherence trajectory groups. The balance of covariates between oral and injectable DMAs before and after IPTW was checked against a standardized difference threshold of 0.25. RESULTS: The study cohort consisted of 1,700 MS patients who were initiated with oral (15.8%) or injectable (84.2%) DMAs between 2010 and 2012. The adherence rates (PDC≥0.8) in oral fingolimod and injectable DMA users were found to be 64.7% and 50.8%, respectively. The GBTM grouped individuals in the study cohort into three adherence trajectories - rapid discontinuers (23.5%), complete adherers (49.9%), and slow decliners (26.6%). The multinomial logistic regression model with stabilized IPTW revealed that oral fingolimod users had higher odds to be a complete adherer (adjusted odds ratio [AOR]: 2.78, 95% CI: 1.85-4.16) or a slow discontinuer (AOR: 2.62, 95% CI: 1.70-4.05) than injectable DMA users. CONCLUSIONS: Oral DMA fingolimod was associated with better adherence than injectable DMAs across group-based trajectories. Further research is warranted to evaluate the adherence trajectories with newer oral DMAs introduced in the last decade for MS.

Antimuscarinic Discontinuation in Patients with Overactive Bladder in Nursing Homes: A Retrospective Study of Medicare Beneficiaries.

INTRODUCTION: Although antimuscarinics form the first-line therapy in overactive bladder (OAB), little is known regarding antimuscarinic discontinuation among OAB patients in nursing homes. This study examined treatment patterns and predictors of antimuscarinic discontinuation among long-term nursing home (LTNH) residents with OAB. METHODS: The study cohort included LTNH residents (defined as residents staying ≥ 101 consecutive days) from the Minimum Data Set linked 2013-2015 Medicare claims data. Patients with OAB were defined by OAB-related claims and medication codes. Treatment patterns and discontinuation (medication gap ≥ 30 days) were characterized by examining OAB-specific antimuscarinics prescribed during LTNH stays. The Andersen Behavioral Model was used to identify predisposing, enabling and need factors that predict discontinuation. Kaplan-Meier curves and multivariable Cox proportional hazards regression model were used to assess the unadjusted and adjusted times to discontinuation, respectively, among different antimuscarinics. RESULTS: The mean age of the study cohort (n = 11,012) was 81.6 years (± 8.5), 74.6% were female, and 89.8% were non-Hispanic White. The mean duration of nursing home stay was 530.1 (± 268.4) days. The most commonly prescribed OAB-specific antimuscarinic was oxybutynin (69.8%). Overall, 66.5% of the study cohort discontinued the index antimuscarinic. Multivariable Cox PH regression analysis revealed that compared to LTNH residents who initiated treatment with oxybutynin, treatment discontinuation was lower with solifenacin or fesoterodin and discontinuation was more frequent when treatment was initiated with tolterodine, darifenacin or trospium compared with oxybutynin. In addition, several need factors (comorbidities, medication use and anticholinergic burden, etc.) were associated with antimuscarinic discontinuation. CONCLUSION: About  two-thirds of LTNH residents with OAB discontinued their index antimuscarinic during their nursing home stay. There was significant variation in discontinuation based on the index antimuscarinic agent with lowest risk of discontiuation with solifenacin and fesoterodin. Concerted efforts to optimize antimuscarinic use are needed to improve the management of OAB in nursing homes.

Factors Associated with Prescribing Oral Disease Modifying Agents in Multiple Sclerosis: a Real-world Analysis of Electronic Medical Records.

BACKGROUND: Little is known about the factors associated with the selection of Disease Modifying Agents (DMA) for the management of Multiple Sclerosis (MS) since the introduction of oral DMAs in 2010. OBJECTIVES: To examine the factors associated with initiation of oral DMAs in patients with MS using data from electronic medical records (EMR). METHODS: A retrospective longitudinal study was conducted using TriNetX, a federated EMR network of over 38 million patients from the US, from 2009-2019. Adult (≥18 years) patients with MS from the United States were identified using a MS diagnosis (ICD-9-CM: 340 or ICD-10-CM: G35) and a newly prescribed DMA with a one-year baseline period. Patients with new DMA prescriptions were classified as oral or injectable users based on their index medication. A multivariable logistic regression model was used to determine the predisposing (age category, sex, race, and ethnicity), enabling (time-period), and need factors (comorbidities, MS symptoms, symptomatic medication, and healthcare utilization) associated with initiation of an oral versus injectable DMA. RESULTS: The study cohort consisted of 7,511 MS patients with a newly prescribed DMA, of whom most were 18-44 years old (48.33%), female (75.18%), and white (80.92%). About 42.32% of MS patients were diagnosed with at least one comorbidity (mean±SD: 0.86±1.37). Two thirds (66.32%) of the patients with MS started injectable DMAs, and the remaining one third (33.68%) started oral DMAs. Multivariable regression revealed that middle-aged (45-64 years; Adjusted Odds Ratio [aOR]=0.88; 95% Confidence Interval [CI]: 0.79-0.98) and older adults (≥65 years; aOR=0.67, 95% CI: 0.53-0.84) were associated with a decreased likelihood of receiving oral DMAs. The presence of general symptoms (aOR=1.26, 95% CI: 1.10-1.45) and cerebellar symptoms (aOR=1.56, 95% CI: 1.26-1.93) was associated with an increased likelihood of an oral DMA. However, the presence of sensory symptoms (aOR: 0.72, 95% CI: 0.59-0.88) was associated with a decreased likelihood of an oral DMA. Comorbidities such as renal failure (aOR=0.16, 95%% 0.04-0.62), obesity (aOR=0.60, 95% CI: 0.45-0.80), drug abuse (aOR=0.61, 95% CI: 0.38-0.99), and other neurological disorders (aOR=0.82, 95% CI: 0.69-0.96) were associated with a decreased likelihood of receiving an oral DMA prescription. While the use of analgesics (aOR=0.78, 95% CI: 0.69-0.88) was associated with decreased likelihood, the use of antispasmodics (aOR=1.14, 95% CI: 1.01-1.28) was associated with an increased likelihood of receiving an oral DMA. Relative to the time-period when first oral DMAs entered into the market (2010-11), with time, the likelihood of prescribing oral DMA increased by multiple folds (2012-13, aOR=4.30, 95% CI: 3.08-6.00; 2014-15, aOR=19.34, 95% CI: 14.10-26.54; 2016-17, aOR=17.63, 95% CI: 12.76-24.35; and 2018-19, aOR=20.73, 95% CI: 14.64-29.37). CONCLUSIONS: Oral DMA use steadily increased over the years, with one in three MS patients receiving oral agents. Both demographic and clinical factors were associated with the initiation of oral DMA over injectable DMA.

Use of disease modifying agents in patients with multiple sclerosis: Analysis of ten years of national data.

BACKGROUND: Disease modifying agents (DMAs) are used to reduce relapses and decrease disability progression in Multiple Sclerosis (MS) patients. However, limited national level data exists regarding the prescribing patterns for MS, especially after the introduction of oral DMAs. OBJECTIVE: This study examined the prescribing patterns and trends of DMAs using national level data and determined the factors associated with prescribing DMAs among MS patients in the United States. METHODS: This cross-sectional study utilized 2006-2015 National Ambulatory Medical Care Survey (NAMCS) data to examine office-based visits involving MS (ICD-9-CM code 340). Descriptive weighted analyses were performed to assess the prescribing patterns of DMAs. Multivariable logistic regression model within the conceptual framework of Andersen Behavioral Model was used to determine the factors associated with prescribing of DMAs among MS patients. RESULTS: An estimated 8.5 million (95% Confidence Interval [CI] 7.01-10.09 million) MS patient visits were identified from 2006 to 2015. During the ten-year study period, 3.84 million (45%) MS visits involved prescribing of DMAs. The majority of DMA prescriptions were injectables (78%), followed by infusions (11%) and orals (11%). Oral DMAs use increased (from 11% in 2010-2011 to 40% in 2014-2015), whereas the use of injectable DMAs decreased (from 96% in 2006-2007 to 52% in 2014-2015) during the study period. Multivariable analyses revealed that predisposing (age and region) and enabling (physician specialty) factors were significantly associated with prescribing of DMAs among MS patients. Visits to neurologists (Odds Ratio [OR] 6.61, 95% CI 3.66-11.93) were associated with higher odds of being prescribed with DMAs. CONCLUSION: During the ten-year study period, increasing use of oral DMAs and declining use of injectable DMAs was observed. Both predisposing and enabling factors influenced the prescribing of DMAs. With increasing availability of oral DMAs, the DMAs use is likely to increase among MS patients.