Efficacy and Safety of Dual Blockade of the Renin-Angiotensin-Aldosterone System in Diabetic Kidney Disease: A Meta-Analysis.

INTRODUCTION: Current guidelines recommend renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of diabetic kidney disease (DKD). However, evidence suggests that the combined use of RAAS blockers may be associated with increased rates of adverse events. OBJECTIVES: Our objective was to examine the efficacy and safety of dual blockade of the RAAS in patients with DKD. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) published between January 1990 and January 2018 sourced via the PubMed, EMBASE, and Cochrane Library databases. RCTs were included if they investigated the efficacy and safety of dual blockade therapy compared with monotherapy in patients with DKD. Random effects models were used in meta-analysis to account for heterogeneities in effect sizes across the reviewed studies. Analyses were stratified by blood pressure and albuminuria. We further conducted subgroup analyses by considering various combinations of RAAS inhibitors. RESULTS: Based on 42 RCTs with 14,576 patients, dual RAAS blockade therapy was associated with significant decreases in blood pressure, albuminuria, and proteinuria. However, dual therapy was not superior to monotherapy in terms of reductions in all-cause mortality, cardiovascular mortality, or progression to end-stage renal disease (ESRD). Significant increases in serum potassium and rates of hyperkalemia and hypotension were more common in patients treated with dual therapy. However, glomerular filtration rates (GFR) did not decrease significantly with dual therapy. In subgroup analysis, an angiotensin-converting enzyme inhibitor (ACEI) plus an angiotensin-receptor blocker (ARB) or a direct renin inhibitor (DRI) plus an ACEI/ARB did not significantly increase the risk of hyperkalemia, hypotension, and adverse events, and the risk of hypotension increased significantly within the normotensive subgroup but not within the hypertensive subgroup. The risk of hyperkalemia increased significantly in patients with DKD with macroalbuminuria but not in those with microalbuminuria. CONCLUSION: Dual inhibition therapy is superior to monotherapy for blood pressure control and urine protein reduction, though such superiority does not translate into improvements in longer-term outcomes, such as reduced progression to ESRD, all-cause mortality, and cardiovascular mortality. An ACEI plus an ARB or a DRI plus an ACEI/ARB may be a safe and effective therapy for patients with DKD, and combination therapy may be suitable for patients with DKD and hypertension and microalbuminuria.

A qualitative comparison of DSM depression criteria to language used by older church-going African-Americans.

OBJECTIVE: Depression in late life is associated with substantial suffering, disability, suicide risk, and decreased health-related quality of life. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), a depression diagnosis is derived from a constellation of symptoms that may be described differently by different people. For example, the DSM language may be inadequate in capturing these symptoms in certain populations such as African-Americans, whose rates of depression misdiagnosis is high. METHODS: This study reports the findings from a church-based, qualitative study with older African-Americans (n = 50) regarding the language they use when discussing depression and depression treatment, and how this compares to the DSM-IV depression criteria. Content analyses of the in-depth discussions with African-American male and female focus group participants resulted in a deeper understanding of the language they used to describe depression. This language was then mapped onto the DSM-IV depression criteria. RESULTS: While some words used by the focus group participants mapped well onto the DSM-IV criteria, some of the language did not map well, such as language describing irritability, negative thought processes, hopelessness, loneliness, loss of control, helplessness, and social isolation. CONCLUSIONS: The focus group setting provided insight to the language used by older, church-going African-Americans to describe depression. Implications include the advantages of using qualitative data to help inform clinical encounters with older African-Americans.

With a little help from my friends?: racial and gender differences in the role of social support in later-life depression medication adherence.

BACKGROUND: Social support has been shown to be an important factor in improving depression symptom outcomes, yet less is known regarding its impact on antidepressant medication adherence. This study sought to evaluate the role of perceived social support on adherence to new antidepressant medication prescriptions in later-life depression. METHODS: Data from two prospective observational studies of participants ≥60 years old, diagnosed with depression, and recently prescribed a new antidepressant (N = 452). Perceived social support was measured using a subscale of the Duke Social Support Index and medication adherence was assessed using a validated self-report measure. RESULTS: At four-month follow up, 68% of patients reported that they were adherent to antidepressant medication. Examining the overall sample, logistic regression analysis demonstrated no significant relationship between perceived social support and medication adherence. However, when stratifying the sample by social support, race, and gender, adherence significantly differed by race and gender in those with inadequate social support: Among those with low social support, African-American females were significantly less likely to adhere to depression treatment than white females (OR = 4.82, 95% CI = 1.14-20.28, p = 0.032) and white males (OR = 3.50, 95% CI = 1.03-11.92, p = 0.045). CONCLUSIONS: There is a significant difference in antidepressant medication adherence by race and gender in those with inadequate social support. Tailored treatment interventions for low social support should be sensitive to racial and gender differences.

Predictors of Antidepressant Nonadherence Among Older Veterans With Depression.

OBJECTIVE: Most depression among older adults is treated in primary care, and many patients do not adhere to medication treatment. The U.S. Department of Veterans Affairs (VA) has recently introduced initiatives to address such treatment gaps. This study examined patient-reported antidepressant nonadherence during the acute treatment period (first four months after a prescription) and identified predictors of nonadherence in a sample of older veterans. METHODS: This was a prospective, observational study of 311 participants ages 60 and older who received care at three VA medical centers and who had a diagnosis of clinically significant depression and were given a new outpatient antidepressant prescription. Participants completed an initial interview and a follow-up interview at four months after treatment recommendation. Antidepressant adherence was measured with a well-validated self-report measure. RESULTS: At four months, 29% of participants reported nonadherence to their antidepressant medication. In unadjusted analyses, nonadherence was significantly associated with being African American, having no spouse or significant other, having greater general medical comorbidity, and receiving the prescription in a primary care setting (versus a specialty mental health setting). In logistic regression models controlling for several variables (demographic, illness, and functional status variables; type of antidepressant; contact with a therapist; medical setting; and site of recruitment), two predictors remained significantly associated with nonadherence: African-American race (odds ratio [OR]=4.23, p<.001) and general medical comorbidity (OR=1.33, p=.002). CONCLUSIONS: The two main predictors of nonadherence among older adults with depression were African-American race and general medical comorbidity. Results suggest that significant needs remain for important patient subgroups to improve antidepressant adherence.

The Association Between Benzodiazepine Use and Depression Outcomes in Older Veterans.

Benzodiazepines (BZDs) are commonly prescribed to older adults with depression, but it is unknown whether they improve antidepressant (AD) adherence or depressive symptoms. We followed 297 older veterans diagnosed with depression and provided a new AD medication prospectively for 4 months. Data include validated self-report measures and VA pharmacy records. At initial assessment, 20.5% of participants were prescribed a BZD. Those with a BZD prescription at baseline were significantly more likely than those without to have a personality disorder, schizophrenia spectrum disorder, or other anxiety disorder, and higher depressive symptom and anxiety symptom scale scores on average. In adjusted regressions, BZD use was not significantly associated with AD adherence, any improvement in depressive symptoms, or a 50% reduction in depressive symptoms. Our results suggest BZD use concurrent with AD treatment does not significantly improve depressive outcomes in older veterans.

Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm.

IMPORTANCE: Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear. OBJECTIVE: To determine the absolute mortality risk increase and number needed to harm (NNH) (ie, number of patients who receive treatment that would be associated with 1 death) of antipsychotic, valproic acid and its derivatives, and antidepressant use in patients with dementia relative to either no treatment or antidepressant treatment. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case-control study was conducted in the Veterans Health Administration from October 1, 1998, through September 30, 2009. Participants included 90,786 patients 65 years or older with a diagnosis of dementia. Final analyses were conducted in August 2014. EXPOSURES: A new prescription for an antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant (46,008 medication users). MAIN OUTCOMES AND MEASURES: Absolute change in mortality risk and NNH over 180 days of follow-up in medication users compared with nonmedication users matched on several risk factors. Among patients in whom a treatment with medication was initiated, mortality risk associated with each agent was also compared using the antidepressant group as the reference, adjusting for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics. Secondary analyses compared dose-adjusted absolute change in mortality risk for olanzapine, quetiapine, and risperidone. RESULTS: Compared with respective matched nonusers, individuals receiving haloperidol had an increased mortality risk of 3.8% (95% CI, 1.0%-6.6%; P < .01) with an NNH of 26 (95% CI, 15-99); followed by risperidone, 3.7% (95% CI, 2.2%-5.3%; P < .01) with an NNH of 27 (95% CI, 19-46); olanzapine, 2.5% (95% CI, 0.3%-4.7%; P = .02) with an NNH of 40 (95% CI, 21-312); and quetiapine, 2.0% (95% CI, 0.7%-3.3%; P < .01) with an NNH of 50 (95% CI, 30-150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%-16.0%; P < .01) with an NNH of 8 (95% CI, 6-12) for haloperidol users to 3.2% (95% CI, 1.6%-4.9%; P < .01) with an NNH of 31 (95% CI, 21-62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%-6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%-2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%-3.0%; P = .047). CONCLUSIONS AND RELEVANCE: The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose.

Mindfulness-based cognitive therapy with older adults: an exploratory study.

An 8-week mindfulness-based cognitive therapy (MBCT) group for older adults with depression and/or anxiety is described. This article is based on an exploratory study of this therapeutic approach and changes in participants' symptoms associated with participation. Pre-post data from 5 MBCT groups showed significant improvements in reported anxiety, ruminative thoughts, and sleep problems and a reduction in depressive symptoms. Case examples are presented to illustrate these symptom changes. Findings showed that this nonpharmacological intervention is acceptable to older adults and is associated with positive changes. Suggestions are provided for both practitioners and researchers interested in using MBCT with older adults.

The association between race and gender, treatment attitudes, and antidepressant treatment adherence.

OBJECTIVES: We examined the associations between treatment attitudes and beliefs with race-gender differences in antidepressant adherence. METHODS: Subjects (n = 186) were African-American and White subjects aged ≥60 years, diagnosed with clinically significant depression, and had a new outpatient primary care recommendation for antidepressant treatment. Antidepressant adherence was assessed using the Brief Medication Questionnaire. Attitudes and beliefs were assessed using the Patients Attitudes Toward and Ratings of Care for Depression, two items rating perceived medication importance, and a modified version of the Stigma Scale for Receiving Psychological Help. RESULTS: African-American men and women had significantly greater concerns about antidepressants and significantly less understanding about treatment than White women. African-American men had significantly more negative attitudes toward healthcare providers than African-American and White women. African-American women were more likely than White men and women to endorse a medication other than their antidepressant as most important. Whereas some race-gender differences were found in personal spirituality, no group differences were found in perceived stigma. In a logistic regression model adjusted for key baseline variables, White women were significantly more adherent to antidepressants than African-American women (OR = 3.05, 95% CI = 1.06-8.81). Fewer concerns about antidepressants and indicating the antidepressant as the most important medication were both significantly associated with adherence. After including either of these two variables, the adherence difference between White women and African-American women was no longer significant (OR = 2.56, 95% CI = 0.84-7.80). CONCLUSIONS: Concerns about antidepressants and the importance of antidepressant medication are associated with adherence and are potentially modifiable through improved patient-provider communication, psycho-education, and therapeutic interventions.

The role of the occupational therapist in the management of neuropsychiatric symptoms of dementia in clinical settings.

Neuropsychiatric symptoms (NPS) of dementia include aggression, agitation, depression, anxiety, delusions, hallucinations, apathy, and disinhibition. NPS affect dementia patients nearly universally across dementia stages and etiologies. They are associated with poor patient and caregiver outcomes, including increased health care utilization, excess morbidity and mortality, and earlier nursing home placement, as well as caregiver stress, depression and reduced employment. There are no FDA-approved medications for NPS, but it is a common clinical practice to use psychotropic medications such as antipsychotics, to control symptoms; however, antipsychotics show only modest efficacy in improving NPS and have significant risks for patients, including side effects and mortality. Nonpharmacologic treatments are considered first-line by multiple medical bodies and expert consensus, as they show evidence for efficacy and have limited potential for adverse effects. Ideally, nonpharmacological management of NPS in clinical settings occurs in multidisciplinary teams, where occupational therapists play an important collaborative role in the care of the person with dementia. Our group has articulated an evidence-informed structured approach to the management of NPS that can be integrated into diverse practice settings and used by providers of various disciplines. The "DICE" (Describe, Investigate, Create, and Evaluate) approach is inherently patient- and caregiver-centered, as patient and caregiver concerns are integral to each step of the process. DICE offers a clinical reasoning approach through which providers can more efficiently and effectively choose optimal treatment plans. The purpose of this paper is to describe the role of the occupational therapy in using the DICE approach for NPS management.

Racial differences in adherence to antidepressant treatment in later life.

OBJECTIVE: Although antidepressants are an effective treatment for later-life depression, older patients often choose not to initiate or to discontinue medication treatment prematurely. Although racial differences in depression treatment preferences have been reported, little is known about racial differences in antidepressant medication adherence among older patients. DESIGN: Prospective, observational study comparing antidepressant adherence for older African American and white primary care patients. PARTICIPANTS: A total of 188 subjects age 60 and older, diagnosed with clinically significant depression with a new recommendation for antidepressant treatment by their primary care physician. MEASUREMENT: Study participants were assessed at study entry and at the 4-month follow-up (encompassing the acute treatment phase). Depression medication adherence was based on a well-validated self-report measure. RESULTS: At the 4-month follow-up, 61.2% of subjects reported that they were adherent to their antidepressant medication. In unadjusted and two of the three adjusted analyses, African American subjects (n = 82) had significantly lower rates of 4-month antidepressant adherence than white subjects (n = 106). African American women had the lowest adherence rates (44.4%) followed by African American men (56.8%), white men (65.3%), and white women (73.7%). In logistic regression models controlling for demographic, illness, and functional status variables, significant differences persisted between African American women and white women in reported 4-month antidepressant adherence (OR: 3.58, 95% CI: 1.27-10.07, Wald χ(2) = 2.42, df = 1, p <0.02). CONCLUSIONS: The results demonstrate racial and gender differences in antidepressant adherence in older adults. Depression treatment interventions for older adults should take into account the potential impact of race and gender on adherence to prescribed medications.

Mortality risk with the use of atypical antipsychotics in later-life bipolar disorder.

INTRODUCTION: In recent years, concerns about the use of antipsychotic medications in dementia have grown. There is limited data on mortality risk of atypical antipsychotics for other psychiatric disorders of later life such as bipolar disorder. METHODS: Data were derived from the national Department of Veterans Affairs registries for older patients with bipolar disorder (≥65 years) with a new start of an atypical antipsychotic (risperidone, olanzapine, or quetiapine) or valproic acid and derivatives during fiscal years 2001-2008. Six-month mortality rates were compared for individual drug groups. RESULTS: The sample included 4717 patients. The risperidone cohort had the highest mortality rate (11.8 per 100 person-years) with the quetiapine and valproic acid cohorts having the lowest (5.3 and 4.6 per 100 person-years, respectively). Various methods to adjust for baseline differences including propensity models showed similar patterns. CONCLUSIONS: Among older patients with bipolar disorder, there may be differences in mortality risks among individual antipsychotic agents.

Using a pharmacy-based intervention to improve antipsychotic adherence among patients with serious mental illness.

BACKGROUND: Similar to patients with other chronic disorders, patients with serious mental illness (SMI) are often poorly adherent with prescribed medications. OBJECTIVE: We conducted a randomized controlled trial examining the effectiveness of a pharmacy-based intervention (Meds-Help) in increasing antipsychotic medication adherence among Department of Veterans Affairs (VA) patients with SMI. We also examined the impact of Meds-Help on psychiatric symptoms, quality of life, and satisfaction with care. METHODS: We enrolled 118 patients from 4 VA facilities with schizophrenia, schizoaffective, or bipolar disorder who were on long-term antipsychotics but had antipsychotic medication possession ratios (MPRs) <0.8 in the prior year. Patients were randomized to usual care (UC; n = 60) or the pharmacy-based intervention (Meds-Help; n = 58). We reassessed adherence at 6 and 12 months, at which time patients completed Positive and Negative Symptom Scales (PANSS), Quality of Well-being Scales (QWB), and Client Satisfaction Questionnaires (CSQ-8). RESULTS: Prior to enrollment, Meds-Help and UC patients had mean antipsychotic MPRs of 0.54 and 0.55, respectively. At 6 months, mean MPRs were 0.91 for Meds-Help and 0.64 for UC patients; at 12 months, they were 0.86 for Meds-Help and 0.62 for UC patients. In multivariate analyses adjusting for patient factors, Meds-Help patients had significantly higher MPRs at 6 and 12 months (P < .0001). There were no significant differences between groups in PANSS, QWB, or CSQ-8 scores, but power to detect small effects was limited. CONCLUSIONS: Congruent with prior studies of patients with other disorders, a practical pharmacy-based intervention increased antipsychotic adherence among patients with SMI. However, SMI patients may require additional care management components to improve outcomes.

Enhanced identification of eligibility for depression research using an electronic medical record search engine.

PURPOSE: Electronic medical records (EMRs) have become part of daily practice for many physicians. Attempts have been made to apply electronic search engine technology to speed EMR review. This was a prospective, observational study to compare the speed and clinical accuracy of a medical record search engine vs. manual review of the EMR. METHODS: Three raters reviewed 49 cases in the EMR to screen for eligibility in a depression study using the electronic medical record search engine (EMERSE). One week later raters received a scrambled set of the same patients including 9 distractor cases, and used manual EMR review to determine eligibility. For both methods, accuracy was assessed for the original 49 cases by comparison with a gold standard rater. RESULTS: Use of EMERSE resulted in considerable time savings; chart reviews using EMERSE were significantly faster than traditional manual review (p=0.03). The percent agreement of raters with the gold standard (e.g. concurrent validity) using either EMERSE or manual review was not significantly different. CONCLUSIONS: Using a search engine optimized for finding clinical information in the free-text sections of the EMR can provide significant time savings while preserving clinical accuracy. The major power of this search engine is not from a more advanced and sophisticated search algorithm, but rather from a user interface designed explicitly to help users search the entire medical record in a way that protects health information.

"No-shows": who fails to follow up with initial behavioral health treatment?

OBJECTIVE: We sought to determine what demographic and clinical factors are associated with receipt of initial mental health treatment. STUDY DESIGN AND METHODS: A total of 1177 patients completed structured clinical interviews (Michigan Screening for Treatment and Research Triage) when they called to authorize mental health benefits. Measures included age, sex, alcohol use, drug use, anxiety, depression, medical history, behavioral health treatment history, psychosocial stressors, functioning, and suicidality. Multivariate analyses determined the association between these variables and a behavioral health claim within 90 days of the interview. RESULTS: Among those completing interviews, 85% attended initial mental health treatment. Factors significantly associated with increased odds of treatment initiation were good self-rated health (odds ratio [OR] = 1.70; 95% confidence interval [CI] = 1.15, 2.50), support of family or friends (OR = 1.71; 95% CI = 1.11, 2.65), previous outpatient mental health visits (OR = 1.56; 95% CI = 1.11, 2.19), and recent alcohol use (OR = 1.41; 95% CI = 1.00, 1.97). Factors associated with decreased odds of treatment initiation were recent period of total disability (OR = 0.62; 95% CI = 0.45, 0.87), any previous suicide attempt (OR = 0.56; 95% CI = 0.36, 0.87), 6 or more physician visits for medical reasons this year (OR = 0.64; 95% CI = 0.44, 0.92), and legal problems (OR = 0.31; 95% CI = 0.16, 0.61). In multivariate analyses, family support, history of medical visits, and recent alcohol use were no longer significant predictors. CONCLUSIONS: Most individuals in this insured population who completed an initial telephone assessment had an initial behavioral health claim. However, patients with greater health or social service needs were at higher risk for not obtaining treatment, suggesting the need for greater outreach and attention by providers and insurers.