Unfilled Prescriptions of Medicare Beneficiaries: Prevalence, Reasons, and Types of Medicines Prescribed.

BACKGROUND: Despite the proven efficacy of prescription regimens in reducing disease symptoms and preventing or minimizing complications, poor medication adherence remains a significant public health problem. Medicare beneficiaries have high rates of chronic illness and prescription medication use, making this population particularly vulnerable to nonadherence. Failure to fill prescribed medication is a key component of nonadherence. OBJECTIVES: To (1) determine the rates of self-reported failure to fill at least 1 prescription among a sample of Medicare beneficiaries in 2004, (2) identify the reasons for not filling prescribed medication, (3) examine the characteristics of Medicare beneficiaries who failed to fill their prescription(s), and (4) identify the types of medications that were not obtained. METHODS: The study is a secondary analysis of the 2004 Medicare Current Beneficiary Survey (MCBS), an ongoing national panel survey conducted by the Centers for Medicare & Medicaid Services (CMS). Medicare beneficiaries living in the community (N = 14,464) were asked: "During the current year [2004], were there any medicines prescribed for you that you did not get (please include refills of earlier prescriptions as well as prescriptions that were written or phoned in by a doctor)?" Those who responded "yes" to this question (n = 664) were asked to identify the specific medication(s) not obtained. Rates of failure to fill were compared by demographic and income categories and for respondents with versus without self-reported chronic conditions, identified by asking respondents if they had ever been told by a doctor that they had the condition. Weighted population estimates for nonadherence were calculated using Professional Software for SUrvey DAta ANalysis for Multi-stage Sample Designs (SUDAAN) to account for the MCBS multistage stratified cluster sampling process. Unweighted counts of the prescriptions not filled by therapeutic class were calculated using Statistical Analysis Software (SAS). RESULTS: In 2004, an estimated 1.6 million Medicare beneficiaries (4.4%) failed to fill or refill 1 or more prescriptions. The most common reasons cited for failure to fill were: "thought it would cost too much" (55.5%), followed by "medicine not covered by insurance" (20.2%), "didn't think medicine was necessary for the condition" (18.0%), and "was afraid of medicine reactions/contraindications" (11.8%). Rates of failure to fill were significantly higher among Medicare beneficiaries aged 18 to 64 years eligible through Social Security Disability Insurance (10.4%) than among beneficiaries aged 65 years or older (3.3%, P < 0.001). Rates were slightly higher for women than for men (5.0 vs. 3.6%, P = 0.001), for nonwhite than for white respondents (5.5% vs. 4.2%, P = 0.010), and for dually eligible Medicaid beneficiaries than for those who did not have Medicaid coverage (6.3% vs. 4.0% P = 0.001). Failure-to-fill rates were significantly higher among beneficiaries with psychiatric conditions (8.0%, P < 0.001); arthritis (5.2%, P < 0.001); cardiovascular disease (5.2%, P = 0.003); and emphysema, asthma, or chronic obstructive pulmonary disease (6.6%, P < 0.001) than among respondents who did not report those conditions, and the rate for respondents who reported no chronic conditions was 2.5%. Rates were higher for those with more self-reported chronic conditions (3.2%, 4.0%, 4.3%, and 5.9% for those with 1, 2, 3, and 4 or more conditions, respectively, P < 0.001). Among the prescriptions not filled (993 prescriptions indentified by 664 respondents), central nervous system agents, including nonsteroidal anti-inflammatory drugs, were most frequently identified (23.6%, n = 234), followed by cardiovascular agents (18.3%, n = 182) and endocrine/metabolic agents (6.5%, n = 65). Of the reported unfilled prescriptions, 8.1% were for antihyperlipidemic agents, 5.4% were for antidepressant drugs, 4.6% were for antibiotics, and 29.9% were for unidentified therapy classes. CONCLUSION: Most Medicare beneficiaries fill their prescriptions, but some subpopulations are at significantly higher risk for nonadherence associated with unfilled prescriptions, including working-age beneficiaries, dual-eligible beneficiaries, and beneficiaries with multiple chronic conditions. Self-reported unfilled prescriptions included critical medications for treatment of acute and chronic disease, including antihyperlipidemic agents, antidepressants, and antibiotics. DISCLOSURES: This study was funded by the U.S. Department of Education's National Institute on Disability and Rehabilitation Research, Field Initiated Research Grant H133G070055. However, the analysis and the interpretation of these findings do not necessarily represent the policy of the Department of Education and are not endorsed by the federal government. All authors contributed approximately equally to the study concept and design. Tuleu performed the majority of the data collection, with assistance from Kennedy. Kennedy interpreted the data, with assistance from Tuleu and Mackay. Kennedy and Mackay wrote the majority of the manuscript, with assistance from Tuleu. Kennedy made the majority of the changes in revision of the manuscript.

Implementation of a primary care physician-led Cavity Clinic using silver diamine fluoride.

OBJECTIVES: Early childhood caries (ECC) disproportionately affects lower socioeconomic status households. In this article, we describe a novel intervention utilizing physician-applied silver diamine fluoride (SDF) in a primary care "Cavity Clinic." METHODS: Building on literature review and expert consultation, Cavity Clinic using SDF for children without dentists was implemented in a family medicine residency setting. Process outcomes were evaluated through chart review and structured field notes. RESULTS: From December 2017 to December 2018, 30 patients have been treated. Their average age is 5.5 years (2-9), 82 percent are African American, and all are insured by Medicaid. Most have severe ECC. Thirty-eight percent have successfully established dental homes through participation. CONCLUSIONS: It is feasible and acceptable for physicians to treat ECC with SDF in a primary care setting. Partnership with an on-site hygienist is helpful but physician-only sessions were still beneficial. This strategy holds potential for addressing the epidemic of ECC.

Analysis of the Intrinsically Disordered N-Terminus of the DNA Junction-Resolving Enzyme T7 Endonuclease I: Identification of Structure Formed upon DNA Binding.

The four-way (Holliday) DNA junction of homologous recombination is processed by the symmetrical cleavage of two strands by a nuclease. These junction-resolving enzymes bind to four-way junctions in dimeric form, distorting the structure of the junction in the process. Crystal structures of T7 endonuclease I have been determined as free protein, and the complex with a DNA junction. In neither crystal structure was the N-terminal 16-amino acid peptide visible, yet deletion of this peptide has a marked effect on the resolution process. Here we have investigated the N-terminal peptide by inclusion of spin-label probes at unique sites within this region, studied by electron paramagnetic resonance. Continuous wave experiments show that these labels are mobile in the free protein but become constrained on binding a DNA junction, with the main interaction occurring for residues 7-10 and 12. Distance measurements between equivalent positions within the two peptides of a dimer using PELDOR showed that the intermonomeric distances for residues 2-12 are long and broadly distributed in the free protein but are significantly shortened and become more defined on binding to DNA. These results suggest that the N-terminal peptides become more organized on binding to the DNA junction and nestle into the minor grooves at the branchpoint, consistent with the biochemical data indicating an important role in the resolution process. This study demonstrates the presence of structure within a protein region that cannot be viewed by crystallography.

A software toolkit and interface for performing stable isotope labeling and top3 quantification using Progenesis LC-MS.

Numerous software packages exist to provide support for quantifying peptides and proteins from mass spectrometry (MS) data. However, many support only a subset of experimental methods or instrument types, meaning that laboratories often have to use multiple software packages. The Progenesis LC-MS software package from Nonlinear Dynamics is a software solution for label-free quantitation. However, many laboratories using Progenesis also wish to employ stable isotope-based methods that are not natively supported in Progenesis. We have developed a Java programming interface that can use the output files produced by Progenesis, allowing the basic MS features quantified across replicates to be used in a range of different experimental methods. We have developed post-processing software (the Progenesis Post-Processor) to embed Progenesis in the analysis of stable isotope labeling data and top3 pseudo-absolute quantitation. We have also created export ability to the new data standard, mzQuantML, produced by the Proteomics Standards Initiative to facilitate the development and standardization process. The software is provided to users with a simple graphical user interface for accessing the different features. The underlying programming interface may also be used by Java developers to develop other routines for analyzing data produced by Progenesis.

Residence in coal-mining areas and low-birth-weight outcomes.

The objective of this study was to estimate the association between residence in coal mining environments and low birth weight. We conducted a cross-sectional, retrospective analysis of the association between low birth weight and mother's residence in coal mining areas in West Virginia. Birth data were obtained from the West Virginia Birthscore Dataset, 2005-2007 (n = 42,770). Data on coal mining were from the US Department of Energy. Covariates regarding mothers' demographics, behaviors, and insurance coverage were included. We used nested logistic regression (SUDAAN Proc Multilog) to conduct the study. Mothers who were older, unmarried, less educated, smoked, did not receive prenatal care, were on Medicaid, and had recorded medical risks had a greater risk of low birth weight. After controlling for covariates, residence in coal mining areas of West Virginia posed an independent risk of low birth weight. Odds ratios for both unadjusted and adjusted findings suggest a dose-response effect. Adjusted findings show that living in areas with high levels of coal mining elevates the odds of a low-birth-weight infant by 16%, and by 14% in areas with lower mining levels, relative to counties with no coal mining. After covariate adjustment, the persistence of a mining effect on low-birth-weight outcomes suggests an environmental effect resulting from pollution from mining activities. Air and water quality assessments have been largely missing from mining communities, but the need for them is indicated by these findings.

Prenatal diagnosis of monosomy 1p36: a focus on brain abnormalities and a review of the literature.

Monosomy 1p36 is an increasingly recognized chromosomal anomaly. We describe two patients with monosomy 1p36 who had brain abnormalities detected on prenatal ultrasound. The first patient was ascertained prenatally with ultrasound abnormalities, including ventriculomegaly, a single umbilical artery, a unilateral club foot, a ventricular septal defect, and intra-uterine growth retardation. Amniocentesis showed a normal karyotype. A postnatal MRI showed moderate to severe non-obstructive hydrocephalus, bilateral colpocephaly, and abnormal myelination of the anterior limb of the internal capsule. A postnatal karyotype demonstrated a deletion of 1p36.3 that was not detected prenatally due to low resolution. Molecular studies by array comparative genome hybridization (CGH) identified a terminal deletion of approximately 10 Mb. Our second patient was a fetus who had brain abnormalities suggestive of holoprosencephaly identified on prenatal ultrasound. Amniocentesis showed 46,XX,der(1)t(1;20)(p36.1;p12.2), that was found to be maternally inherited. Fetal autopsy demonstrated hydrocephalus, focal polymicrogyria, and cerebellar hypoplasia. However, holoprosencephaly was not confirmed. In addition to describing two patients with monosomy 1p36 who had abnormal brain anatomy on prenatal ultrasounds, we review the literature of other prenatally detected patients with monosomy 1p36 and review brain abnormalities seen both prenatally and postnatally.

Clinical and molecular cytogenetic characterization of four patients with unbalanced translocation der(1)t(1;22)(p36;q13).

Deletion of chromosome 1p36 is the most commonly observed terminal deletion in humans with a frequency of 1 in 5,000 in the general population. In contrast, 22q13 duplications are rare and only a few cases have been reported. Unbalanced translocations resulting in monosomy 1p36 and a trisomy of 22q13.3 are, thus far, unreported in the literature. Here we present the clinical data and the results of array CGH and FISH analysis of four patients with unbalanced translocations t(1;22)(p36;q13) inherited from unrelated balanced translocation carrier parents. The sizes of the imbalances ranged from 0.12 Mb to nearly 10 Mb. One balanced translocation carrier parent had disruption of the period homolog 3 (PER3) gene and reported sleep disturbances. Overall, patients tended to have more features consistent with deletion of 1p36 than duplication of 22q.

Unexpected complexity at breakpoint junctions in phenotypically normal individuals and mechanisms involved in generating balanced translocations t(1;22)(p36;q13).

Approximately one in 500 individuals carries a reciprocal translocation. Balanced translocations are usually associated with a normal phenotype unless the translocation breakpoints disrupt a gene(s) or cause a position effect. We investigated breakpoint junctions at the sequence level in phenotypically normal balanced translocation carriers. Eight breakpoint junctions derived from four nonrelated subjects with apparently balanced translocation t(1;22)(p36;q13) were examined. Additions of nucleotides, deletions, duplications, and a triplication identified at the breakpoints demonstrate high complexity at the breakpoint junctions and indicate involvement of multiple mechanisms in the DNA breakage and repair process during translocation formation. Possible detailed nonhomologous end-joining scenarios for t(1;22) cases are presented. We propose that cryptic imbalances in phenotypically normal, balanced translocation carriers may be more common than currently appreciated.

Unfilled prescriptions of medicare beneficiaries: prevalence, reasons, and types of medicines prescribed.

BACKGROUND: Despite the proven efficacy of prescription regimens in reducing disease symptoms and preventing or minimizing complications, poor medication adherence remains a significant public health problem. Medicare beneficiaries have high rates of chronic illness and prescription medication use, making this population particularly vulnerable to nonadherence. Failure to fill prescribed medication is a key component of nonadherence. OBJECTIVES: To (1) determine the rates of self-reported failure to fill at least 1 prescription among a sample of Medicare beneficiaries in 2004, (2) identify the reasons for not filling prescribed medication, (3) examine the characteristics of Medicare beneficiaries who failed to fill their prescription(s), and (4) identify the types of medications that were not obtained. METHODS: The study is a secondary analysis of the 2004 Medicare Current Beneficiary Survey (MCBS), an ongoing national panel survey conducted by the Centers for Medicare & Medicaid Services (CMS). Medicare beneficiaries living in the community (N = 14,464) were asked: "During the current year [2004], were there any medicines prescribed for you that you did not get (please include refills of earlier prescriptions as well as prescriptions that were written or phoned in by a doctor)?" Those who responded "yes" to this question (n = 664) were asked to identify the specific medication(s) not obtained. Rates of failure to fill were compared by demographic and income categories and for respondents with versus without self-reported chronic conditions, identified by asking respondents if they had ever been told by a doctor that they had the condition. Weighted population estimates for nonadherence were calculated using Professional Software for Survey Data Analysis for Multi-stage Sample Designs (SUDAAN) to account for the MCBS multistage stratified cluster sampling process. Unweighted counts of the prescriptions not filled by therapeutic class were calculated using Statistical Analysis Software (SAS). RESULTS: In 2004, an estimated 1.6 million Medicare beneficiaries (4.4%) failed to fill or refill 1 or more prescriptions. The most common reasons cited for failure to fill were: "thought it would cost too much" (55.5%), followed by "medicine not covered by insurance" (20.2%), "didn't think medicine was necessary for the condition" (18.0%), and "was afraid of medicine reactions/contraindications" (11.8%). Rates of failure to fill were significantly higher among Medicare beneficiaries aged 18 to 64 years eligible through Social Security Disability Insurance (10.4%) than among beneficiaries aged 65 years or older (3.3%, P < 0.001). Rates were slightly higher for women than for men (5.0 vs. 3.6%, P = 0.001), for nonwhite than for white respondents (5.5% vs. 4.2%, P = 0.010), and for dually eligible Medicaid beneficiaries than for those who did not have Medicaid coverage (6.3% vs. 4.0% P = 0.001). Failure-to-fill rates were significantly higher among beneficiaries with psychiatric conditions (8.0%, P < 0.001); arthritis (5.2%, P < 0.001); cardiovascular disease (5.2%, P = 0.003); and emphysema, asthma, or chronic obstructive pulmonary disease (6.6%, P < 0.001) than among respondents who did not report those conditions, and the rate for respondents who reported no chronic conditions was 2.5%. Rates were higher for those with more self-reported chronic conditions (3.2%, 4.0%, 4.3%, and 5.9% for those with 1, 2, 3, and 4 or more conditions, respectively, P < 0.001). Among the prescriptions not filled (993 prescriptions indentified by 664 respondents), central nervous system agents, including nonsteroidal anti-inflammatory drugs, were most frequently identified (23.6%, n = 234), followed by cardiovascular agents (18.3%, n = 182) and endocrine/metabolic agents (6.5%, n = 65). Of the reported unfilled prescriptions, 8.1% were for antihyperlipidemic agents, 5.4% were for antidepressant drugs, 4.6% were for antibiotics, and 29.9% were for unidentified therapy classes. CONCLUSION: Most Medicare beneficiaries fill their prescriptions, but some subpopulations are at significantly higher risk for nonadherence associated with unfilled prescriptions, including working-age beneficiaries, dual-eligible beneficiaries, and beneficiaries with multiple chronic conditions. Self-reported unfilled prescriptions included critical medications for treatment of acute and chronic disease, including antihyperlipidemic agents, antidepressants, and antibiotics.

Monosomy 1p36 deletion syndrome.

Monosomy 1p36 results from a heterozygous deletion of the most distal chromosomal band on the short arm of chromosome 1. Occurring in approximately 1 in 5,000 live births, monosomy 1p36 is the most common terminal deletion observed in humans. Monosomy 1p36 is associated with mental retardation, developmental delay, hearing impairment, seizures, growth impairment, hypotonia, and heart defects. The syndrome is also characterized by several distinct dysmorphic features, including large anterior fontanels, microcephaly, brachycephaly, deep-set eyes, flat nose and nasal bridge, and pointed chin. Several genes have been proposed as causative for individual features of the phenotype. In addition, based upon molecular characterization of subjects with monosomy 1p36, several mechanisms for the generation and stabilization of terminal deletions have been proposed.