Kidney transplantation in patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single-center data suggests that 5%-15% of adult TSC patients are kidney transplant recipients. METHODS: This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC-associated kidney failure. We utilized descriptive statistics to characterize the frequency of first-time kidney transplant waitlisting and transplantation among persons with TSC and the Fine-Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist. RESULTS: We identified 200 TSC-associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two-thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96-0.99]). 91.8% of kidney transplant recipients survived 1-year post-transplant with a functioning allograft. CONCLUSIONS: The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1-year post transplant patient and allograft survival.

Subsequent kidney transplant after pediatric heart transplant: Prevalence and risk factors.

Pediatric heart failure and transplantation carry associated risks for kidney failure and potential need for kidney transplant following pediatric heart transplantation (KT/pHT). This retrospective, United Network of Organ Sharing study of 10,030 pediatric heart transplants (pHTs) from 1987 to 2020 aimed to determine the incidence of waitlisting for and completion of KT/pHT, risk factors for KT/pHT, and risk factors for nonreceipt of a KT/pHT. Among pHT recipients, 3.4% were waitlisted for KT/pHT (median time of 14 years after pHT). Among those waitlisted, 70% received a KT/pHT, and 18% died on the waitlist at a median time of 0.8 years from KT/pHT waitlisting (median age of 20 years). Moderate-high sensitization at KT/pHT waitlisting (calculated panel reactive antibody, ≥ 20%) was associated with a lower likelihood of KT/pHT (adjusted hazard ratio, 0.67; 95% confidence interval, 0.47-0.95). Waitlisting for heart transplantation simultaneously with kidney transplant (adjusted hazard ratio, 3.73; 95% confidence interval, 2.01-6.92) was associated with increased risk of death on the KT/pHT waitlist. While the prevalence of KT/pHT is low, there is substantial mortality among those waitlisted for KT/pHT. These findings suggest a need to consider novel risk factors for nonreceipt of KT/pHT and death on the waitlist in prioritizing criteria/guidelines for simultaneous heart-kidney transplantation.

Urinary Tract Infection Frequency and Prescription Prophylaxis in Females and Males with Recurrent Urinary Tract Infection.

Females and males with recurrent urinary tract infections may receive prescription prophylaxis to reduce the infection frequency. Little is known about how prescription prophylaxis differs between patients meeting and exceeding the minimum threshold for recurrent urinary tract infections. The objectives of this study were to estimate the association between infection frequency and receipt of prescription prophylaxis and describe the type of prescription prophylaxis initiated. This observational study used de-identified fully-insured commercial insurance data from the Midwest from 2003-2016 to identify females and males under age 64 with recurrent urinary tract infections. The patients were categorized as having three or more urinary tract infections in twelve months or only two infections in six months. Multiple logistic regression models were used to determine the association between the infection frequency and receipt of prophylaxis. The frequency of the type of prophylaxis initiated was measured. The odds of receiving prophylaxis were greater in the females and males with three or more infections compared to the patients with only two infections. Estrogen prophylaxis was initiated at a higher rate in females aged 45-63 with two infections than the females with three or more infections. Prescription prophylaxis in females and males with recurrent urinary tract infections differs between those meeting and exceeding the minimum frequency threshold.

Kidney Imaging Surveillance in Commercially Insured Patients With Tuberous Sclerosis Complex.

BACKGROUND: Kidney disease has historically been the primary source of early mortality in adults with tuberous sclerosis complex (TSC). Kidney imaging surveillance promotes early detection of lesions requiring intervention. We describe kidney imaging frequency in relationship to patient-level characteristics for commercially insured patients with TSC in the United States. METHODS: This retrospective observational study used 2003 to 2016 enrollment and claims data from a de-identified fully insured commercial health insurer. Patients with TSC less than 65 years were included. The patient-level kidney imaging rate was calculated as the number of kidney imaging procedures divided by length of continuous enrollment. A multiple linear regression model was used to determine the relationship between imaging rate and progression of TSC-associated kidney disease, number of specialists seen, and nephrologist care. RESULTS: At least half of the 70 patients with TSC included in the study were aged 16 years or younger. Over a follow-up period of up to 14 years, the median kidney imaging rate was 0.13 procedures per year with 43% (N = 30) of patients lacking evidence of kidney imaging during the observation period. Imaging frequency increased with progression of TSC-associated kidney disease, more specialists, and nephrologist care (P < 0.05 for all three in regression model). CONCLUSIONS: A substantial percentage of patients with TSC in the United States are at risk for delayed detection of kidney manifestations due to infrequent kidney imaging surveillance. Multispecialty care, including neurologists, may positively affect kidney surveillance rates.

Medication-Related Problems Identified Through Continuous Medication Monitoring.

Community pharmacists performing Continuous Medication Monitoring (CoMM) systematically monitor each new prescription and refill dispensed for medication-related problems. The objectives for this study were to describe medication-related problems identified through CoMM and drug classes involved in problems. This 12-month pilot study used dispensing and clinical records from a single independent U.S. community pharmacy. Clinical records contain medication-related problems documented by the pharmacists. Problems identified for patients filling at least one prescription at the pharmacy and having at least one medication-related problem during the study period were included. A total of 8439 medication-related problems were identified for 1566 patients, an average of 5.4 problems per patient. Over 63% of problems were nonadherence. The drug class most often involved in problems was the central nervous system and analgesic class. Community pharmacists performing CoMM identified medication-related problems that might otherwise have gone undetected.

Geographic variation in inhaled corticosteroid use for children with persistent asthma in Medicaid.

OBJECTIVE: Geographic variation in the rates of inhaled corticosteroid (ICS) use for children with persistent asthma in Medicaid has been reported, but the source of this variation is unknown. The objective of this study was to quantify the geographic variation in ICS use for children with persistent asthma in Medicaid that remains after adjusting for the characteristics of children in an area. METHODS: Data from the 2005-2007 Medicaid Analytic eXtract files were used. Frequent fills of short-acting beta2-agonist (SABA) were used to identify children 5-18 years of age with persistent asthma across the United States. A child was considered to have used an ICS if the child initially filled an ICS following frequent SABA use. Areas were determined using published methods, and the unadjusted ICS rate and the area treatment ratio for ICS, which adjusted for demographic and clinical characteristics, were calculated for each area. RESULTS: Of 15,917 children, 13% used an ICS. The median unadjusted ICS rate for all areas was 10% but ranged from 0% to 64%. ICS use was less than expected for more than half of the areas based on the characteristics of the children in the area, but use was nearly five times what was expected in some areas. Areas with higher than expected ICS use were found contiguous to areas with lower than expected use. CONCLUSIONS: Geographic variation in ICS not attributable to the demographic and clinical characteristics of the children in an area exists and could prove useful in the struggle to reduce asthma exacerbation rates.

Continuous Medication Monitoring (CoMM): A foundational model to support the clinical work of community pharmacists.

BACKGROUND: Under the Continuous Medication Monitoring (CoMM) approach, community pharmacists prevent, identify, resolve, and document drug therapy problems during the dispensing process. OBJECTIVE: To describe the patients receiving CoMM interventions and the pattern of delivery of CoMM interventions. METHODS: Pharmacy dispensing and clinical records were reviewed for patients filling at least one prescription and receiving at least one continuous medication monitoring intervention at a community pharmacy from April 2014 through March 2015. The proportion of patients receiving an intervention type and the number of interventions per patient were computed. RESULTS: Nearly 2500 patients received 16,986 continuous medication monitoring interventions over the year. The average age of the patients receiving the interventions was 59.1 years, and they filled an average of 8.0 unique medications. An average of 6.8 interventions was delivered to each patient. About half (49.7%) of interventions addressed drug therapy problems. The pharmacists delivered 3.0 patient counseling and education and 3.4 drug therapy problem interventions per patient on average. CONCLUSION: There are many opportunities to improve patients' medication use that can be identified and addressed under a Continuous Medication Monitoring model. Movement to this model of practice is desirable, but changes are needed to facilitate the shift.

Cost-utility analysis of physician-pharmacist collaborative intervention for treating hypertension compared with usual care.

OBJECTIVE: To estimate long-term costs and outcomes attributable to a physician-pharmacist collaborative intervention compared with physician management alone for treating essential hypertension. METHODS: A Markov model cohort simulation with a 6-month cycle length to predict acute coronary syndrome, stroke, and heart failure throughout lifetime was performed. A cohort of 399 patients was obtained from two prospective, cluster randomized controlled clinical trials implementing physician-pharmacist collaborative interventions in community-based medical offices in the Midwest, USA. Framingham risk equations and other algorithms were used to predict the vascular diseases. SBP reduction due to the interventions deteriorated until 5 years. Direct medical costs using a payer perspective were adjusted to 2015 dollar value, and the main outcome was quality-adjusted life years (QALYs); both were discounted at 3%. The intervention costs were estimated from the trials, whereas the remaining parameters were from published studies. A series of sensitivity analyses including changing patient risks of vascular diseases, probabilistic sensitivity analysis, and a cost-effectiveness acceptability curve were performed. RESULTS: The lifetime incremental costs were $26 807.83 per QALY (QALYs gained = 0.14). The intervention provided the greatest benefit for the high-risk patients, moderate benefit for the trial patients, and the lowest benefit for the low-risk patients. If a payer is willing to pay $50 000 per QALY gained, in 48.6% of the time the intervention would be cost-effective. CONCLUSION: Team-based care such as a physician-pharmacist collaboration appears to be a cost-effective strategy for treating hypertension. The intervention is most cost-effective for high-risk patients.

Application of a framework for determining number of drugs.

BACKGROUND: There are many different methodologies used in the literature for determining the number of drugs used by a patient, and many are incompletely described. This may be attributable to the lack of a framework to help investigators choose and describe their methods and the lack of evidence on the implications of the choice. The purpose of the study was to propose a framework and illustrate how that framework can be used to create and succinctly describe various approaches to counting the number of drugs used by patients and to examine the impact of varying individual components of the framework on the resulting drug count. METHODS: The three component framework requires specification of scope, uniqueness, and timeframe. The framework was applied to Medicare beneficiaries admitted for acute myocardial infarction in 2008. Drug use was ascertained by Part D prescription drug event files. A default measure for drug count was established, and fourteen additional measures were created by separately altering individual components of the default to illustrate the application of the framework and understand how these changes impacted drug count. Median drug counts and the frequency distributions of beneficiaries experiencing a change in count from default were produced for each measure. RESULTS: The median drug count for the default measure was 4. Alteration of the timeframe component had the largest impact on drug counts, with a look-back period of 180 days producing a median count of 8 and changing the count by at least two for 73 % of patients. Variations of the other components had less impact. CONCLUSION: Our framework is intended to be used by investigators to select an approach to counting number of drugs in their studies. Extending the timeframe over which fills from a pharmacy refill database could be counted toward the drug count produced the greatest changes in the number of drugs.

Development of a medication monitoring attitude measure using a mixed methods item development process.

OBJECTIVES: Medication monitoring is important for safe and effective medication use; however, no attitudinal measure exists for a health care provider's medication monitoring attitude. The objectives of this study were to (1) create a measure of a community pharmacist medication monitoring attitude; (2) test concurrent validity using a validated measure of medication monitoring behaviours; and (3) report community pharmacist attitudes towards medication monitoring. METHODS: A mixed methods item development process was employed to generate Likert-type items from qualitative interviews. Following item review and piloting, a four-contact survey, including 20 6-point Likert-type items and the four-item Behavioral Pharmaceutical Care Scale monitoring domain, was mailed to 599 randomly sampled US community pharmacists from the state of Iowa. Exploratory factor analysis, Pearson's correlation and descriptive statistics were used to address study objectives. KEY FINDINGS: There were 254 (42.4%) returned and usable surveys. Factor analysis yielded two domains, a seven-item, positively worded internal (α = 0.819) and an eight-item, negatively worded external domain (α = 0.811). Both domains were positively correlated with the monitoring domain of the Behavioral Pharmaceutical Care Scale supporting convergent validity. Overall, respondents had a positive internal monitoring attitude with a mean of 4.62 (0.68), although many practiced in an environment less conducive to monitoring, as evident by a mean of 3.13 (0.88). Pharmacists were more oriented towards medication side effect and effectiveness monitoring than nonadherence monitoring. CONCLUSIONS: The mixed methods item development process created a reliable and valid measure of a pharmacist's medication monitoring attitude. While pharmacists had an overall positive medication monitoring attitude, improvements are needed to bolster adherence monitoring and make pharmacy environments more conducive to monitoring.

Provider Visits for Asthma: Potential Barriers for Insured Children.

OBJECTIVE: The barriers to provider visits for asthma in insured children are not well understood. Our objective was to examine the relationship between parent, family, and child attributes and asthma visits in insured children. METHODS: This retrospective, cross-sectional analysis of 2007 Medical Expenditure Panel Survey-Household Component data included insured children 0-17 years old reported to have active asthma. We summed the number of provider visits during which asthma was treated or diagnosed to represent the frequency of asthma visits during the year. Probit models were used to estimate the relationship between parent, family, and child attributes and asthma visits. RESULTS: Seventy percent of the 542 children did not have an asthma visit during the year. Children with parents employed full time were 16 percentage points less likely to have an asthma visit than children whose parents were not working (P=.01). CONCLUSION: Many insured children go more than a year without seeing a provider for their asthma, signaling that insurance is not sufficient to guarantee children will receive asthma monitoring. The attributes related to asthma visits suggest potential barriers that providers might want to consider to increase participation in asthma visits.

Instrumental variable methods to assess quality of care the marginal effects of process-of-care on blood pressure change and treatment costs.

BACKGROUND: Hypertension is poorly controlled. Team-based care and changes in the process of care have been proposed to address these quality problems. However, assessing care processes is difficult because they are often confounded even in randomized behavioral studies by unmeasured confounders based on discretion of health care providers. OBJECTIVE: To evaluate the effects of process measures including number of counseling sessions about lifestyle modification and number of antihypertensive medications on blood pressure change and payer-perspective treatment costs. METHODS: Data were obtained from two prospective, cluster randomized controlled clinical trials (Trial A and B) implementing physician-pharmacist collaborative interventions compared with usual care over six months in community-based medical offices in the Midwest. Multivariate linear regression models with both instrumental variable methods and as-treated methods were utilized. Instruments were indicators for trial and study arms. Models of blood pressure change and costs included both process measures, demographic variables, and clinical variables. RESULTS: The analysis included 496 subjects. As-treated methods showed no significant associations between process and outcomes. The instruments used in the study were insufficient to simultaneously identify distinct process effects. However, the post-hoc instrumental variable models including one process measure at a time while controlling for the other process demonstrated significant associations between the processes and outcomes with estimates considerably larger than as-treated estimates. CONCLUSIONS: Instrumental variable methods with combined randomized behavioral studies may be useful to evaluate the effects of different care processes. However, substantial distinct process variation across studies is needed to fully capitalize on this approach. Instrumental variable methods focusing on individual processes provided larger and stronger outcome relationships than those found using as-treated methods which are subject to confounding.

Factors related to receipt of well-child visits in insured children.

Our objective was to identify factors related to receipt of the recommended number of well-child visits in insured children. We hypothesized parent insurance status would be related to receipt of well-child visits, with those with uninsured parents more likely to have fewer visits than recommended. Data for the study came from the 2007 Medical Expenditure Panel Survey-Household Component. The sample included children <18 years of age with full-year insurance coverage and parents who were insured or uninsured the entire year. The outcome variable indicated whether children had received fewer than the recommended number of well-child visits in physician offices or outpatient departments. Parent, family, and child characteristics were measured. Forty-eight percent of the 4,650 children included in the study had fewer well-child visits than recommended. Children whose parents did not visit a physician during the year and children whose parents had not completed high school were more likely to miss recommended visits. Parent insurance status did not affect well-child visits. We identified child, family, and parent factors influencing well-child visits in insured children, including the parent's own use of physician visits. Contrary to our hypothesis, well-child visits were not influenced by parent insurance status. Determining which insured children are at greater risk of missing recommended well-child visits aids policymakers in identifying those who may benefit from interventions to improve use of preventive care.

Effect of Medicare Part D and insurance type on Medicare beneficiary access to prescription medication and use of prescription cost-saving measures.

OBJECTIVES: To examine how prescription drug access and use of prescription cost-saving measures changed after Medicare Part D was implemented and to determine their predictors in Medicare beneficiaries with different insurance types. DESIGN: Repeated cross-sectional study. SETTING: United States in 2005 and 2007. PATIENTS: Medicare beneficiaries aged 65 years or older (n = 1,220 in 2005 and n = 1,024 in 2007). INTERVENTION: Web-based surveys using nonprobability samples. MAIN OUTCOME MEASURES: Access to prescription drugs and use of seven costsaving measures. RESULTS: Significantly fewer participants stopped taking a prescription because of cost, applied to an assistance program, received free prescription samples, and had limited prescription access in 2007 compared with 2005. Use of cost-saving measures by Medicare Part D patients was more comparable with that by uninsured participants than patients with employer-based drug coverage. One-third of all participants and almost one-half of Medicare Part D participants had requested a less expensive prescription. Among those participants, 70% received a less expensive prescription and most thought it worked about the same as the more expensive prescription. CONCLUSION: Prescription drug access and use of cost-saving measures improved somewhat following the implementation of Medicare Part D, but some access problems continued to exist for Part D participants. Requests for less expensive prescriptions were common and frequently resulted in satisfactory switches.

Impact of cost sharing on prescription drugs used by Medicare beneficiaries.

BACKGROUND: Incentive-based prescription drug cost sharing can encourage seniors to use generic medications. Little information exists about prescription drug cost sharing and generic use in employer-sponsored plans after the implementation of Medicare Part D. OBJECTIVES: To compare prescription drug cost sharing across prescription insurance type for Medicare beneficiaries after Medicare Part D, to assess the impact of that cost sharing on the number of medications used, and to examine how generic utilization rates differ before and after Medicare Part D and across the type of insurance. METHODS: This longitudinal study of Medicare beneficiaries aged 65 years and older used Web-based surveys administered in 2005 and 2007 by Harris Interactive((R)) to collect information on prescription drug coverage and medication use. Co-payment plans were categorized as low, medium, or high co-payment plans. Multiple regression was used to assess the impact of co-payment rank on the number of prescription drugs. t-Tests and analysis of variance were used to compare generic use over time and between coverage types. RESULTS: One thousand two hundred twenty and 1024 respondents completed the baseline and follow-up surveys, respectively. Among 3-tier co-payment plans, brand drug co-payments were higher for Part D plans ($26 for preferred brand and $55 for nonpreferred brand) than employer-based plans ($20 for preferred brand and $39 for nonpreferred brand). Co-payment was not a significant predictor for the number of prescription drugs. Generic use was lowest among beneficiaries in employer plans both before and after Part D. In 2007, generic use among beneficiaries with Part D was not significantly different from the generic use for beneficiaries with no drug coverage. CONCLUSIONS: Medicare beneficiaries in Part D had higher cost sharing amounts than those with employer coverage, but higher cost sharing was not significantly linked to lower prescription use. Generic use for Part D beneficiaries was higher than that for beneficiaries with employer coverage but the same as that for beneficiaries without drug coverage.

Effect of cost sharing on prescription drug use by Medicare beneficiaries prior to the Medicare Drug Benefit and potential adverse selection in the benefit.

OBJECTIVE: To (1) describe prescription drug cost sharing and benefit structures faced by seniors before implementation of the Medicare drug benefit, (2) examine the relationship between prescription drug benefit structure and prescription drug use by seniors prior to Medicare drug benefit, and (3) examine factors predicting intention to enroll in the Medicare drug benefit. DESIGN: Cross-sectional study. SETTING: Internet-based survey administered on behalf of the researchers by Harris Interactive in October 2005. PARTICIPANTS: Harris Interactive maintains a panel of individuals who have opted to participate in online surveys. Individuals from this panel who were English speaking, 65 years of age or older, U.S. residents, and enrolled in Medicare were invited to participate. INTERVENTION: The survey collected information on prescription coverage, prescription use, intention to enroll in the Medicare drug benefit, health status, and demographics. MAIN OUTCOME MEASURES: Number of prescriptions used by a beneficiary in the month before the survey and the intention of the beneficiary to enroll in the Medicare drug benefit. RESULTS: Beneficiaries were enrolled in plans with a wide variety of benefit structures and cost-sharing amounts. Prescription drug use fell with higher copayment ranks and average coinsurance but not at the P < 0.05 level. Among poorer individuals, the relationship between copayment rank and use was significant. Individuals reporting worse health status and a higher number of prescriptions indicated greater intention to enroll in the Medicare drug benefit, suggesting possible adverse selection. CONCLUSION: Prescription use decreased as cost sharing increased with mixed significance. There was evidence of potential adverse selection in the Medicare drug benefit.

Once-daily abacavir in place of twice-daily administration.

OBJECTIVE: To review the safety and efficacy of a once-daily dosage regimen for abacavir, a nucleoside reverse transcriptase inhibitor. DATA SOURCES: English-language MEDLINE and Iowa Drug Information Service database reports were accessed from 1966 to March 2005. International Pharmaceutical Abstracts was searched from 1970 to March 2005. The key words used in all searches were abacavir and Ziagen. Article bibliographies were used to identify additional relevant articles. The Internet was searched to identify abstracts of poster and oral presentations that have not yet been published. The manufacturer was also contacted to obtain unpublished information. STUDY SELECTION AND DATA EXTRACTION: Publications were included that provided information related to the safety and efficacy of abacavir when used once daily. Preference was given to randomized, double-blind, controlled trials comparing once-daily abacavir regimens with other antiretroviral regimens. Abstracts from professional meetings were included for unpublished studies, and conference coverage reviews were included if the abstracts were not available. DATA SYNTHESIS: In trials directly comparing once- and twice-daily abacavir, little difference was shown in the efficacy of the 2 regimens. Despite similar adverse effect profiles, significantly more severe hypersensitivity reactions and severe diarrhea were seen with once-daily abacavir in one trial. CONCLUSIONS: Once-daily administration of abacavir has not been shown to be inferior to twice-daily dosing, but it may put patients at increased risk for severe hypersensitivity reactions and diarrhea. More data are needed to confirm this risk.