Benjamin F. Banahan

Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes

BACKGROUND The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. METHODS We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. RESULTS Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). CONCLUSIONS Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (Funded by the National Institutes of Health and others.).

Potency Trends of Δ9-THC and Other Cannabinoids in Confiscated Marijuana from 1980–1997

The analysis of 35,312 cannabis preparations confiscated in the USA over a period of 18 years for delta-9-tetrahydrocannabinol (delta9-THC) and other major cannabinoids is reported. Samples were identified as cannabis, hashish, or hash oil. Cannabis samples were further subdivided into marijuana (loose material, kilobricks and buds), sinsemilla, Thai sticks and ditchweed. The data showed that more than 82% of all confiscated samples were in the marijuana category for every year except 1980 (61%) and 1981 (75%). The potency (concentration of delta9-THC) of marijuana samples rose from less than 1.5% in 1980 to approximately 3.3% in 1983 and 1984, then fluctuated around 3% till 1992. Since 1992, the potency of confiscated marijuana samples has continuously risen, going from 3.1% in 1992 to 4.2% in 1997. The average concentration of delta9-THC in all cannabis samples showed a gradual rise from 3% in 1991 to 4.47% in 1997. Hashish and hash oil, on the other hand, showed no specific potency trends. Other major cannabinoids [cannabidiol (CBD), cannabinol (CBN), and cannabichromene (CBC)] showed no significant change in their concentration over the years.

Predictors of Medication Nonadherence Among Patients With Diabetes in Medicare Part D Programs: A Retrospective Cohort Study

OBJECTIVES This study examined the prevalence of nonadherence with oral hypoglycemic agents, antihypertensive drugs (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARBs]), and statin medications among Medicare Part D enrollees with diabetes and analyzed the potential demographic and clinical factors that predict medication nonadherence. METHODS This was a retrospective cohort study of Medicare Part D enrollees with diabetes from 6 states (Alabama, California, Florida, Mississippi, New York, and Ohio). Adherence was calculated as the proportion of days covered (PDC; number of days with medication on hand/number of days in the specified time interval). A PDC was derived for each of the 3 categories of medications for patients who had at least 1 claim for the same class of medication. A comorbidity measure was created for each beneficiary using the Deyo-adapted Charlson Comorbidity Index (CCI). Associations between nonadherence and patient characteristics including age, sex, race/ethnicity, and Deyo-adapted CCI were examined. Logistic regression models were constructed to identify predictors of nonadherence. RESULTS The study included 1,888,682 patients with diabetes. The mean (SD) age was 71.6 (11.6) years, and 59.5% (1,123,220/1,888,682) were female. A total of 66.4% (1,254,538/1,888,682) were white, 16.3% (308,158/1,888,682) were black, and 7.8% (147,498/1,888,682) were Hispanic. Estimated rates of non-adherence for oral hypoglycemic agents, ACEIs/ARBs, and statins were 35.1% (386,666/1,101,533), 41.8% (449,561/1,075,285), and 46.4% (447,106/962,877), respectively. In unadjusted analyses, patients aged <65 years, women, black or Hispanic patients, and patients with higher Deyo-adapted CCI were more likely to be nonadherent to all 3 classes of medications. The results were consistent in multivariate analyses, and all results were statistically significant at P < 0.001. CONCLUSIONS In this study of Medicare Part D enrollees with diabetes, patients aged <65 years, women, black or Hispanic patients, and those with higher comorbidity scores were more likely to be nonadherent to medications. Interventions should be developed to improve medication adherence among these subgroups so that patients can achieve the full benefits of prescribed pharmacologic therapies.

Do statins improve outcomes in patients with asthma on inhaled corticosteroid therapy? A retrospective cohort analysis

Objectives Animal studies and clinical trials have examined the potential benefits of statins in asthma management with contradictory results. The objective of this study was to determine if asthma patients on concurrent statins are less likely to have asthma-related hospitalisations. Design A retrospective cohort study using Mississippi Medicaid data for 2002–2004. Participants Asthma patients ≥18 years were identified using the ICD9 code 493.xx from 1 July 2002 through 31 December 2003. The index date for an exposed subject was any date within the identification period, 180 days prior to which the subject had at least one inhaled corticosteroid prescription and at least an 80% adherence rate to statins. Asthma patients on inhaled corticosteroids, but not on statins, were selected as the unexposed population. The two groups were matched and followed for 1 year beginning the index date. Main outcomes measures Patient outcomes in terms of hospitalisations and ER visits were compared using conditional logistic regression. Results After matching, there were 479 exposed subjects and 958 corresponding unexposed subjects. The odds of asthma-related hospitalisation and/or emergency room (ER) visits for asthma patients on concurrent statins were almost half the odds for patients not on statins (OR=0.55; 95% CI (0.37 to 0.84); p=0.0059). Similarly, the odds of asthma-related ER visits were significantly lower for patients on statins (OR=0.48; 95% CI (0.28 to 0.82); p=0.0069). Conclusion The findings suggest beneficial effects of statins in asthma management. Further prospective investigations are required to provide more conclusive evidence.

Tricyclic antidepressant overdose: Conservative management in a community hospital with cost-saving implications

Reports of late-onset cardiovascular complications following tricyclic antidepressant (TCA) overdose have led to a very conservative approach to these patients. Many patients have been hospitalized for continuous cardiac monitoring, regardless of the clinical presentation. Management algorithms based on clinical predictors of outcome have recently been proposed. We used the algorithm developed by Tokarski and Young to retrospectively evaluate the care of 33 TCA overdose patients admitted to our hospital over a 3-year period. We then identified 11 patients who could have been treated on an outpatient basis had the algorithm been employed. Ten were admitted to a monitored unit and spent a mean of 31.6 +/- 15.64 hours on the unit. None of the 11 patients developed complications during their hospital stay. Use of the algorithm would have resulted in an estimated cost savings of 13 hospital days and

Hypertension and stress: A preventive approach

14,000.

Medication Adherence Among Recipients with Chronic Diseases Enrolled in a State Medicaid Program

Abstract The most common approach to hypertension treatment is medication. Medical treatment, however, has been plagued with serious problems regarding detecting cases and maintaining compliance. By definition, the high proportion of cases diagnosed as ‘essential hypertension’ points to our inability to identify the causes of hypertension. This suggests that a psychosocial rather than a medical approach is needed if prevention is to be obtained. Such a preventive approach, based on decreasing the effects of stress, is presented. The first step—identifying individuals over-reactive to stress—was tested using Spielbergers state-trait anxiety model. Employees in five industries were screened for high blood pressure. A systematic sample and all hypertensives (SBP ≥ 160 and/or DBP ≥ 95 mm Hg) completed the State-Trait Anxiety Inventory (STAI). A-Trait as a measure of individual reactiveness to stress showed a weak relationship to hypertension. A-State, a measure of situation specific anxiety, showed a strong relationship to blood pressure. Multiple regression analyses identified obesity and A-State as the two most important modifiable risk factors for inclusion in a preventive program.

Herbal Supplement Information and the Consumer

Limited information is currently available about medication adherence for common chronic conditions among the Medicaid population. The primary objective of this study was to assess medication adherence among Medicaid recipients with depression, diabetes, epilepsy, hypercholesterolemia, and hypertension. Factors influencing adherence were determined. The authors also assessed whether adherence influences the utilization of acute care services. The target population included nonelderly adult recipients (ages 21-64 years) who were continuously enrolled in the Mississippi (MS) Medicaid fee-for-service program from January 1, 2006 to December 31, 2007. Recipients were identified who had a medical services claim with a diagnosis of depression, diabetes, epilepsy, hypercholesterolemia, or hypertension in calendar year 2006. Within each chronic disease sample, medication adherence was determined using calendar year 2007 data for recipients who met inclusion and exclusion criteria. Recipients with adherence ≥80% were classified as adherent. Logistic regression analyses were used to determine the factors that predict medication adherence and the effect of adherence on concurrent all-cause acute care service (ie, hospitalization, emergency room visit) utilization. Approximately 24% of recipients with depression, 35.9% with diabetes, 53.6% with epilepsy, 32% with hypercholesterolemia, and 42.2% with hypertension were adherent. Within each chronic disease sample, males and whites had higher adherence than females and blacks. After controlling for demographic and disease-related covariates, recipients who were adherent had lower concurrent acute care service utilization than nonadherent recipients. Given the inverse relationship between adherence and acute care service utilization, policy makers should consider implementing educational interventions aimed at improving adherence in this underprivileged population.

Making MTM implementable and sustainable in community pharmacy: Is it time for a different game plan?

The purpose of this study was to investigate the consumers search for information in the context of self-care decisions involving herbal supplements, and the preferences for types of information in that context. The nationwide self-administered survey included a series of mock label profiles for use in conjoint analysis, as well as attitudinal items regarding information sources and the perceived gaps in available information regarding herbal supplements. The most frequently mentioned source of information was “friends and relatives” (45%). While few respondents (10% to 20%) actually had utilized conventional health practitioners as a source of information, nearly 70% said that they might use them. The attribute considered in the conjoint analysis that was most often rated as most important was professional recommendation. A majority (73%) of respondents identified “gaps” in the information that is available to them regarding herbal supplements. Implications of the results identify potential areas for policy consideration and future research.

Antecedents and consequences of pharmacy loyalty behavior

Although the literature has demonstrated positive patient outcomes from medication therapy management (MTM), implementing it in community pharmacy continues to be met with significant barriers. To make MTM implementation more attainable, scalable, and sustainable in community pharmacies, this paper puts out a call for the need to identify the proportion of patients who clinically qualify for various levels of intensity of MTM services. This paper presents three proposed levels of MTM: adherence management (lowest level of MTM intensity), interventions on drug-related problems (mid-level MTM intensity), and disease state management (highest level of intensity). It is hypothesized that the lowest levels of MTM intensity would be sufficient to address medication problems in the vast majority of patients and require fewer MTM skills and resources, while the highest levels of MTM intensity (requiring the most skills and resources) would address medication problems in the smallest number of patients whose medication problems could not resolved with lower-intensity MTM. Future research in this area will involve testing previously designed instruments to determine why patients are not adhering to their medication regimen, following patients who have already had their adherence managed with medication synchronization, and tracking patients who will require higher levels of pharmacy services.