Cognitive Function Remains Associated With Functional Impairment in Profound Dementia: Alzheimer Disease and Dementia With Lewy Bodies.

Background and Objectives: The Baylor Profound Mental Status Examination (BPMSE) was developed to assess cognitive function in the profound stage of dementia. The Clinical Dementia Rating (CDR) scale has been widely used in measuring functional performance in dementia. We aimed to determine whether cognitive function is related to overall functional impairment in profound dementia. Methods: We selected 864 patients with probable Alzheimer disease (AD) and 25 patients with possible dementia with Lewy Bodies (DLB) cases with profound dementia by Mini-Mental Status Examination or/and clinical global impression. We used BPMSE to measure cognitive function and the CDR sum-of-boxes (CDR-SB) score to determine overall functional status. We used Spearman rank order correlation to examine the univariate association between CDR-SB and BPMSE in the 2 diagnostic groups separately and multivariable regression analysis to investigate whether BPMSE remained associated with functional status after adjustment for age, sex, education, and APOE ε4 genotype. We expected to see an inverse correlation between BPMSE and CDR-SB scores based on the directionality of the rating scale scoring. Results: In both AD and DLB, total BPMSE scores had a significant inverse correlation with CDR-SB scores (AD: r = -0.453, p < 0.001; DLB: r = -0.489, p = 0.013). It is of interest that in DLB, the "attention" domain of BPMSE had the strongest association with CDR-SB (r = -0.700, p < 0.001) compared with other domains. The multivariable regression models showed that higher BPMSE scores (i.e., better cognitive function) remained significantly correlated with lower CDR-SB scores (i.e., better global function) in AD (CDR-SB: ß = -0.340, p < 0.001), but the regression coefficient for BPMSE did not reach significance in the DLB model (CDR-SB: ß = -0.298, p = 0.174). Discussion: In patients with AD and DLB who enter the profound dementia stage, cognitive function is associated with the severity of functional impairment. The lack of significance for DLB in multivariable regression could be due to small sample size because the correlation magnitude is similar to that in AD.

Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

Changes in Measures of Vestibular and Balance Function and Hippocampus Volume in Alzheimer's Disease and Mild Cognitive Impairment.

OBJECTIVE: To test the hypotheses that people with Alzheimer's disease and mild cognitive impairment have increased frequency of vestibular impairments and decreased hippocampal volume compared with healthy age-matched controls. STUDY DESIGN: Retrospective, with some historical controls. SETTING: Out-patient, tertiary care center. SUBJECTS: People with mild to moderate dementia diagnosed with Alzheimer's disease and with mild cognitive impairment. Main Outcome Measures: A standard clinical battery of objective tests of the vestibular system, and screening for balance; available clinical diagnostic magnetic resonance imaging (MRIs) were reviewed and postprocessed to quantify the left and right hippocampal volumes utilizing both manual segmentation and computer automated segmentation. RESULTS: Study subjects (N = 26) had significantly more vestibular impairments, especially on Dix-Hallpike maneuvers and cervical vestibular evoked myogenic potentials (cVEMP), than historical controls. No differences were found between mild and moderate dementia subjects. Independence on instrumental activities of daily living in subjects with age-normal balance approached statistical differences from subjects with age-abnormal balance. MRI data were available for 11 subjects. Subjects with abnormal cVEMP had significantly reduced left hippocampal MRIs using manual segmentation compared with subjects with normal cVEMP. CONCLUSION: The data from this small sample support and extend previous evidence for vestibular impairments in this population. The small MRI sample set should be considered preliminary evidence, and suggests the need for further research, with a more robust sample and high-resolution MRIs performed for the purpose of hippocampal analysis.

Medication Adherence and Blood Pressure Control: A Scientific Statement From the American Heart Association.

The widespread treatment of hypertension and resultant improvement in blood pressure have been major contributors to the dramatic age-specific decline in heart disease and stroke. Despite this progress, a persistent gap remains between stated public health targets and achieved blood pressure control rates. Many factors may be important contributors to the gap between population hypertension control goals and currently observed control levels. Among them is the extent to which patients adhere to prescribed treatment. The goal of this scientific statement is to summarize the current state of knowledge of the contribution of medication nonadherence to the national prevalence of poor blood pressure control, methods for measuring medication adherence and their associated challenges, risk factors for antihypertensive medication nonadherence, and strategies for improving adherence to antihypertensive medications at both the individual and health system levels.

Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD): A Report of an International Research Collaboration Network.

Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer's disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed.

Cohort Effects in Progression Rate on Cognitive and Functional Measures in an Alzheimer's Disease Clinical Cohort.

BACKGROUND: Accurate prediction of Alzheimer's disease (AD) cognitive and functional outcomes in clinical research requires consistent underlying rates of change over time. OBJECTIVE: To examine cohort effects in AD progression rate over five years of follow-up using a clinical database of probable AD patients. METHODS: Baseline characteristics of three cohorts enrolled from 1995-1999, 2000-2004, and 2005-2009 were compared using ANOVA and chi-square tests. Differences in 5-year decline on the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), the Lawton and Brody Physical Self-maintenance Scale (PSMS), and Activities of Daily Living Scale (ADL) were assessed using longitudinal mixed effects regression, adjusting for age, sex, education, and other relevant clinical characteristics. RESULTS: Cohorts 1 (n = 287), 2 (n = 257), and 3 (n = 374) did not differ on age, race, APOE genotype, or cognitive and functional measures. Educational attainment increased over time (13.4, 14.1, and 14.5 years, respectively, p < 0.001). Anti-dementia drug use at baseline was less common in Cohort 1 (32.2% versus 65.0%, and 66.8%, p < 0.001). The rate of decline in MMSE and CDR-SB did not differ across cohorts. ADAS-Cog scores for Cohort 2 declined more slowly than Cohort 3 (Btime ×cohort2 = -0.91 ± 0.35, p = 0.009), whereas Cohort 1 did not differ from cohort 3 (reference). Cohorts 1 and 2 differed from Cohort 3 in progression rate on the PSMS, but not the IADL. CONCLUSIONS: There were no consistent temporal trends in progression rates over time. Longitudinal data over 15-20 years may be confidently pooled for outcomes analysis, but unexplained variability in rate of decline on some measures may occur.

Spectrum and time course of epilepsy and the associated cognitive decline in MECP2 duplication syndrome.

OBJECTIVE: We characterized the epilepsy features and contribution to cognitive regression in 47 patients with MECP2 duplication syndrome (MDS) and reviewed these characteristics in over 280 MDS published cases. METHODS: The institutional review board approved this retrospective review of medical records and case histories of patients with MDS. RESULTS: The average age at enrollment was 10 ± 7 years. Patients with epilepsy were older (13 ± 7 years vs 8 ± 5 years, p = 0.004) and followed for a longer time (11.8 ± 6.5 years vs 6.3 ± 4.2 years, p = 0.003) than patients without a seizure disorder. Epilepsy affected 22/47 (47%) patients with MDS. It was treatment-refractory and consistent with epileptic encephalopathy in 18/22 (82%) cases. Lennox-Gastaut syndrome (LGS) was present in 12/22 (55%) patients and manifested between late childhood and adulthood in 83% of cases. The emergence of neurologic regression coincided with the onset of epilepsy. The MECP2 duplication size and gene content did not correlate with epilepsy presence, type, age at onset, or treatment responsiveness. CONCLUSION: Epilepsy in MDS is common, often severe, and medically refractory. LGS occurs frequently and may have a late onset. Developmental regression often follows the onset of epilepsy. The MECP2 duplication extent and gene content do not discriminate between patients with or without epilepsy. Our findings inform clinical care and family counseling with respect to early epilepsy recognition, diagnosis, specialty referral, and implementation of aggressive seizure therapy to minimize detrimental effect of uncontrolled seizures on cognitive functions or preexisting neurologic deficits.

Using the 4 Pillars Practice Transformation Program to Increase Pneumococcal Immunizations for Older Adults: A Cluster-Randomized Trial.

OBJECTIVES: To test the effectiveness of a step-by step, evidence-based guide, the 4 Pillars Practice Transformation Program, to increase adult pneumococcal vaccination. DESIGN: Randomized controlled cluster trial (RCCT) in Year 1 (June 1, 2013 to May 31, 2014) and pre-post study in Year 2 (June 1, 2014 to January 31, 2015) with data analyzed in 2016. Baseline year was June 1, 2012, to May 31, 2013. Demographic and vaccination data were derived from deidentified electronic medical record extractions. SETTING: Primary care practices (n = 25) stratified according to metropolitan area (Houston, Pittsburgh), location (rural, urban, suburban), and type (family medicine, internal medicine), randomized to receive the intervention in Year 1 (n = 13) or Year 2 (n = 12). PARTICIPANTS: Individuals aged 65 and older at baseline (N = 18,107; mean age 74.2; 60.7% female, 16.5% non-white, 15.7% Hispanic). INTERVENTION: The 4 Pillars Program, provider education, and one-on-one coaching of practice-based immunization champions. Outcome measures were 23-valent pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) vaccination rates and percentage point (PP) changes in vaccination rates. RESULTS: In the Year 1 RCCT, PPSV vaccination rates increased significantly in all intervention and control groups, with average increases ranging from 6.5 to 8.7 PP (P < .001). The intervention was not related to greater likelihood of PPSV vaccination. In the Year 2 pre-post study, the likelihood of PPSV and PCV vaccination was significantly higher in the active intervention sites than the maintenance sites in Pittsburgh but not in Houston. CONCLUSION: In a RCCT, PPSV vaccination rates increased in the intervention and control groups in Year 1. In a pre-post study, private primary care practices actively participating in the 4 Pillars Practice Transformation Program improved PPSV and PCV uptake significantly more than practices that were in the maintenance phase of the study.

Using the 4 pillars™ practice transformation program to increase adult influenza vaccination and reduce missed opportunities in a randomized cluster trial.

BACKGROUND: An evidence-based, step-by-step guide, the 4 Pillars™ Practice Transformation Program, was the foundation of an intervention to increase adult immunizations in primary care and was tested in a randomized controlled cluster trial. The purpose of this study is to report changes in influenza immunization rates and on factors related to receipt of influenza vaccine. METHODS: Twenty five primary care practices were recruited in 2013, stratified by city (Houston, Pittsburgh), location (rural, urban, suburban) and type (family medicine, internal medicine), and randomized to the intervention (n = 13) or control (n = 12) in Year 1 (2013-14). A follow-up intervention occurred in Year 2 (2014-15). Demographic and vaccination data were derived from de-identified electronic medical record extractions. RESULTS: A cohort of 70,549 adults seen in their respective practices (n = 24 with 1 drop out) at least once each year was followed. Baseline mean age was 55.1 years, 35 % were men, 21 % were non-white and 35 % were Hispanic. After one year, both intervention and control arms significantly (P < 0.001) increased influenza vaccination, with average increases of 2.7 to 6.5 percentage points. In regression analyses, likelihood of influenza vaccination was significantly higher in sites with lower percentages of patients with missed opportunities (P < 0.001) and, after adjusting for missed opportunities, the intervention further improved vaccination rates in Houston (lower baseline rates) but not Pittsburgh (higher baseline rates). In the follow-up intervention, the likelihood of vaccination increased for both intervention sites and those that reduced missed opportunities (P < 0.005). CONCLUSIONS: Reducing missed opportunities across the practice increases likelihood of influenza vaccination of adults. The 4 Pillars™ Practice Transformation Program provides strategies for reducing missed opportunities to vaccinate adults. TRIAL REGISTRATION: This study was registered as a clinical trial on 03/20/2013 at ClinicalTrials.gov, Clinical Trial Registry Number: NCT01868334 , with a date of enrollment of the first participant to the trial of April 1, 2013.

Using the 4 Pillars™ Practice Transformation Program to increase adult Tdap immunization in a randomized controlled cluster trial.

INTRODUCTION: National adult Tdap vaccination rates are low, reinforcing the need to increase vaccination efforts in primary care offices. The 4 Pillars™ Practice Transformation Program is an evidence-based, step-by-step guide to improving primary care adult vaccination with an online implementation tracking dashboard. This study tested the effectiveness of an intervention to increase adult Tdap vaccination that included the 4 Pillars™ Program, provider education, and one-on-one coaching of practice-based immunization champions. METHODS: 25 primary care practices participated in a randomized controlled cluster trial (RCCT) in Year 1 (6/1/2013-5/31/2014) and a pre-post study in Year 2 (6/1/2014-1/31/2015). Baseline year was 6/1/2012-5/31/2013, with data analyzed in 2016. Demographic and vaccination data were derived from de-identified electronic medical record (EMR) extractions. The primary outcomes were vaccination rates and percentage point (PP) changes/year. RESULTS: The cohort consisted of 70,549 patients ⩾18years who were seen in the practices ⩾1 time each year, with a baseline mean age=55years; 35% were men; 56% were non-white; 35% were Hispanic and 20% were on Medicare. Baseline vaccination rate averaged 35%. In the Year 1 RCCT, cumulative Tdap vaccination increased significantly in both intervention and control groups; in both cities, the percentage point increases in the intervention groups (7.7 PP in Pittsburgh and 9.9 PP in Houston) were significantly higher (P<0.001) than in the control groups (6.4 PP in Pittsburgh and 7.6 PP in Houston). In the Year 2 pre-post study, in both cities, active intervention groups increased rates significantly more (6.2 PP for both) than maintenance groups (2.2 PP in Pittsburgh and 4.1 PP in Houston; P<0.001). CONCLUSIONS: An intervention that includes the 4 Pillars™ Practice Transformation Program, staff education and coaching is effective for increasing adult Tdap immunization rates within primary care practices. Clinical Trial Registry Name/Number: NCT01868334.

Designing and evaluating health systems level hypertension control interventions for African-Americans: lessons from a pooled analysis of three cluster randomized trials.

OBJECTIVES: African-Americans (AAs) have a high prevalence of hypertension and their blood pressure (BP) control on treatment still lags behind other groups. In 2004, NHLBI funded five projects that aimed to evaluate clinically feasible interventions to effect changes in medical care delivery leading to an increased proportion of AA patients with controlled BP. Three of the groups performed a pooled analysis of trial results to determine: 1) the magnitude of the combined intervention effect; and 2) how the pooled results could inform the methodology for future health-system level BP interventions. METHODS: Using a cluster randomized design, the trials enrolled AAs with uncontrolled hypertension to test interventions targeting a combination of patient and clinician behaviors. The 12-month Systolic BP (SBP) and Diastolic BP (DBP) effects of intervention or control cluster assignment were assessed using mixed effects longitudinal regression modeling. RESULTS: 2,015 patients representing 352 clusters participated across the three trials. Pooled BP slopes followed a quadratic pattern, with an initial decline, followed by a rise toward baseline, and did not differ significantly between intervention and control clusters: SBP linear coefficient = -2.60±0.21 mmHg per month, p<0.001; quadratic coefficient = 0.167± 0.02 mmHg/month, p<0.001; group by time interaction group by time group x linear time coefficient=0.145 ± 0.293, p=0.622; group x quadratic time coefficient= -0.017 ± 0.026, p=0.525). RESULTS were similar for DBP. The individual sites did not have significant intervention effects when analyzed separately. CONCLUSION: Investigators planning behavioral trials to improve BP control in health systems serving AAs should plan for small effect sizes and employ a "run-in" period in which BP can be expected to improve in both experimental and control clusters.

Screening people in the waiting room for vestibular impairments.

OBJECTIVE: Primary care physicians need good screening tests of the vestibular system to help them determine whether patients who complain of dizziness should be evaluated for vestibular disorders. The goal of this study was to determine whether current, widely used screening tests of the vestibular system predict subsequent performance on objective diagnostic tests of the vestibular system (ENG). METHODS: Of 300 subjects who were recruited from the waiting room of a primary care clinic and were screened there, 69 subjects subsequently volunteered for ENGs in the otolaryngology department. The screening study included age, history of vertigo, head impulse tests, Dix-Hallpike maneuvers, and the Clinical Test of Sensory Integration and Balance with the head still and the head pitching at 0.33 Hz. The ENG included Dix-Hallpike maneuvers, vestibular-evoked myogenic potentials, bithermal water caloric tests, and low-frequency sinusoids in the rotatory chair in darkness. RESULTS: The scores on the screening were related to the total ENG, but odds ratios were not significant for some variables, probably because of the small sample size. CONCLUSIONS: A larger sample may have yielded stronger results, but in general the high odds ratios suggest a relation between the ENG score and Dix-Hallpike responses and between the ENG scores and some Clinical Test of Sensory Integration and Balance responses.

Characteristics, drug combinations and dosages of primary care patients with uncontrolled ambulatory blood pressure and high medication adherence.

Most studies on the prevalence and determinants of resistant hypertension (RH) do not account for white coat hypertension, medication non-adherence, or use of suboptimal treatment dosages. We studied the characteristics, drug combinations, and dosages of patients on at least three antihypertensives of different classes who had uncontrolled blood pressure on 24-hour ambulatory blood pressure monitoring and high medication adherence measured by electronic monitoring. The data were collected as part of the baseline measures of a hypertension control trial. Of 140 monitored primary care patients, all with uncontrolled office blood pressure, 69 (49%) were on at least three antihypertensives of different classes. Of these 69, 15 (22%) were controlled on ambulatory blood pressure monitoring, 20 (29%) were uncontrolled and non-adherent, leaving only 34 (49%) adherent to their medications and having uncontrolled ambulatory hypertension (uncontrolled RH). Thirty-one (91%) of the 34 uncontrolled RH patients were prescribed a diuretic, of which 24 were on hydrochlorothiazide 25 mg. Less than half of the patients on angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or calcium channel blocker were prescribed maximal doses of these agents. Half of the RH can be attributed to white coat effect and poor medication adherence, and all of the remaining patients were on apparently suboptimal drug combinations and/or dosages. Primary care physicians need to be educated regarding the optimal treatment of RH.

Patterns of nonadherence to antihypertensive therapy in primary care.

Nonadherence to medications is an important cause of poor blood pressure control. Long-acting antihypertensive agents could theoretically be beneficial in partially adherent patients, who are commonly seen in contemporary practice. Little has been reported about the duration of drug holidays (DHs) in treated hypertensives outside of generally compliant patients in phase 4 clinical trials. The authors described patterns of nonadherence to single and multiple antihypertensives in a random sample of 120 primary care patients with uncontrolled hypertension. Adherence to up to 3 antihypertensives was measured by electronic monitoring. Frequencies of single-day omissions and DHs of 2 consecutive days (DH2), 3 days (DH3), or ≥4 days (DH≥4) for each drug were calculated. Overall, 89 (74%) of patients had at least a 1-day omission. A single day omission was found in 61.4% of the patients taking 1 drug, followed by DH≥4 (28.1%), DH2 (26.3%), and DH3 (8.8%). In patients using multiple drugs, single-day omissions were also most common, followed by DH≥4, DH2, and DH3. Omissions of ≤3 days comprise on average 74% of all omissions. Although encouraging full adherence remains important, it may be prudent to prescribe long-acting antihypertensive agents, which can compensate for the majority of dose omissions.

Spirituality and confidence to resist substance use among celebrate recovery participants.

Since self-efficacy is a positive predictor of substance use treatment outcome, we investigated whether it is associated with spirituality within a religious 12-step program. This was a cross-sectional survey (N = 91) of 10 different Celebrate Recovery sites held at community churches. The mean spirituality score for those with high confidence was significantly greater than those with low confidence. Spirituality associated with greater confidence to resist substance use (OR = 1.09, 95% CI 1.02-1.17, P < 0.05). So every unit increase of measured spirituality increased the odds of being above the median in self-efficacy by 9%. We conclude that spirituality may be an important explanatory variable in outcomes of a faith-based 12-step recovery program.

Self-efficacy and barriers to multiple behavior change in low-income African Americans with hypertension.

Behavioral risk factors are among the preventable causes of health disparities, yet long-term change remains elusive. Many interventions are designed to increase self-efficacy, but little is known about the effect on long-term behavior change in older, low-income African Americans, especially when facing more problematic barriers. A cohort of 185 low-income African-Americans with hypertension reported barriers they encountered while undergoing a multiple behavior change trial from 2002 to 2006. The purpose of the present study was to explore the relationships between self-efficacy, barriers, and multiple behavior change over time. Higher self-efficacy seemed to be partially helpful for smoking reduction and increasing physical activity, but not for following a low-sodium diet. Addiction was indirectly associated with less reduction in smoking through lower self-efficacy. Otherwise, different barriers were associated with behavior change than were associated with self-efficacy: being "too busy" directly interfered with physical activity and "traditions" with low-sodium diet; however, they were neither the most frequently reported barriers, nor associated with lower self-efficacy. This suggests that an emphasis on self-efficacy alone may be insufficient for overcoming the most salient barriers encountered by older African Americans. Additionally, the most common perceived barriers may not necessarily be relevant to long-term behavioral outcomes.

Factors that influence survival in a probable Alzheimer disease cohort.

INTRODUCTION: This longitudinal study examined multiple factors that influence survival in a cohort of Alzheimer patients followed over two decades. METHODS: Time to death after symptom onset was determined in 641 probable AD patients who were evaluated annually until death or loss to follow-up, and information was entered into a longitudinal database. Date of death was available for everyone including those eventually lost. Baseline variables included age, sex, race, disease severity, a calculated index of rate of initial cognitive decline from symptom onset to cohort entry (pre-progression rate or PPR), years of education, and medical comorbidities (diabetes, hypertension, hyperlipidemia, coronary disease, cerebrovascular disease). Multivariable Cox proportional hazard regression analysis was used to analyze the baseline and/or time dependent association in Mini-mental Status Exam (MMSE) severity, Physical Self Maintenance Scale (PSMS), Persistency Index (PI) of exposure to antipsychotic and antidementia drugs, and psychotic symptoms (hallucinations, delusions) with mortality. RESULTS: Baseline covariates significantly associated with increased survival were younger age (p = .0016), female sex (p = .0001), and a slower PPR (p < .0001). Overall disease severity at baseline, medical comorbidities, and education did not influence time to death. Time-dependent changes in antipsychotic drug use, development of psychotic symptoms, antidementia drug use, and observed MMSE change were not predictive. In the final model the only time-dependent covariate that significantly decreased survival was worsening of functional ability on the PSMS (hazard ratio = 1.10; CI: 1.07-1.11). CONCLUSIONS: In this large AD cohort survival is influenced by age, sex, and the development of functional disability during follow-up. The most important predictor of mortality was a faster rate of cognitive decline at the initial patient visit (PPR). The currently available antidementia drugs do not prolong survival in Alzheimer patients.

Predictors of antihypertensive medication adherence in two urban health-care systems.

BACKGROUND: Most studies on patient-related predictors of adherence used self-reported measures or pharmacy databases to measure adherence. We identified predictors of antihypertensive medication adherence measured by Medication Event Monitoring System (MEMS), the gold standard for adherence assessment, in uncontrolled, predominantly African-American (AA) hypertensives from large urban public and private primary care clinics. METHODS: As part of the baseline data collection of a cluster-randomized trial for hypertension control, we measured adherence in a random sample of 124 participants using MEMS caps. We also included the data of 52 patients in intervention clinics who subsequently completed MEMS monitoring on referral from their provider. Participants were classified as adherent if they took ≥ 80% of all prescribed doses. Multivariate logistic regression was used to predict adherence. RESULTS: Of 176 patients monitored, 61 (34.6%) took <80% of prescribed doses. AA ethnicity (odds ratio (OR) AA vs. Hispanic = 0.36; 95% confidence interval (CI) 0.15-0.86), female sex (OR = 0.38; 95% CI 0.15-0.91), and public clinics as source of care (OR public clinics vs. private clinics = 0.45; 95% CI 0.20-0.97) were independently associated with lower adherence. Higher adherence was seen in patients monitored by clinician order in the intervention clinics (OR intervention sample vs. random baseline sample = 2.15; 95% CI 0.96-4.81) and diabetic patients (OR = 2.05; 95% CI 1.01-4.15). All analyses were adjusted for education, employment status, and other potentially confounding factors. CONCLUSIONS: AA ethnicity, female gender and attending a publicly funded primary care clinic were associated with lower adherence. Whether targeting these groups for special interventions would improve overall adherence needs further study.

Effect of a physician uncertainty reduction intervention on blood pressure in uncontrolled hypertensives--a cluster randomized trial.

BACKGROUND: Clinical inertia, provider failure to appropriately intensify treatment, is a major contributor to uncontrolled blood pressure (BP). Some clinical inertia may result from physician uncertainty over the patient's usual BP, adherence, or value of continuing efforts to control BP through lifestyle changes. OBJECTIVE: To test the hypothesis that providing physicians with uncertainty reduction tools, including 24-h ambulatory BP monitoring, electronic bottle cap monitoring, and lifestyle assessment and counseling, will lead to improved BP control. DESIGN: Cluster randomized trial with five intervention clinics (IC) and five usual care clinics (UCC). SETTING: Six public and 4 private primary care clinics. PARTICIPANTS: A total of 665 patients (63 percent African American) with uncontrolled hypertension (BP ≥140 mmHg/90 mmHg or ≥130/80 mmHg if diabetic). INTERVENTIONS: An order form for uncertainty reduction tools was placed in the IC participants' charts before each visit and results fed back to the provider. OUTCOME MEASURES: Percent with controlled BP at last visit. Secondary outcome was BP changes from baseline. RESULTS: Median follow-up time was 24 months. IC physicians intensified treatment in 81% of IC patients compared to 67% in UCC (p < 0.001); 35.0% of IC patients and 31.9% of UCC patients achieved control at the last recorded visit (p > 0.05). Multi-level mixed effects longitudinal regression modeling of SBP and DBP indicated a significant, non-linear slope difference favoring IC (p (time × group interaction) = 0.048 for SBP and p = 0.001 for DBP). The model-predicted difference attributable to intervention was -2.8 mmHg for both SBP and DBP by month 24, and -6.5 mmHg for both SBP and DBP by month 36. CONCLUSIONS: The uncertainty reduction intervention did not achieve the pre-specified dichotomous outcome, but led to lower measured BP in IC patients.