Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

BACKGROUND: This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive. METHODS: A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors. RESULTS: Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001). DISCUSSION: Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer's disease while considering the burden on the healthcare system.

Sustainable intensification in jeopardy: Transdisciplinary evidence from Malawi.

In Africa, achieving sustainable agricultural intensification-increasing agricultural output without deleterious environmental impacts or converting more land for cultivation-will depend greatly on the actions of smallholder farmers and the policies that influence them. Whatever the future holds, the vast majority of farmers right now are small. Using multiple lines of evidence across disciplines, we examine trends in productivity of land and fertilizers in Malawi. Unfortunately, our effort uncovers disturbing trends that indicate intensification and sustainability are at risk. Two time-series datasets of satellite-based vegetative indices show a generally flat but highly variable trend in the productivity of agricultural land with epochs of steep decline. This is notably despite substantial (and successful) government effort to promote fertilizer use. We also compile evidence from several studies over three decades that use field-level data from farmers and suggest substantial declining maize yield response to fertilizer over time. These trends are consistent with soil degradation, the disappearance of fallow land and minimal investment in rehabilitation practices in densely populated areas, putting agricultural productivity in jeopardy. These signs of the harmful impacts that narrow approaches to productivity improvement may be having in Malawi are an early warning sign to policy makers in Malawi and around the continent that a more holistic and nuanced strategy is necessary for sustainable intensification in agriculture.

Design and Development of a Community-Based, Interdisciplinary, Collaborative Dementia Care Program.

OBJECTIVE: To describe the design, development, and baseline characteristics of enrollees of a home-based, interdisciplinary, dyadic, pilot dementia care program. DESIGN: Single-arm, dementia care intervention in partnership with primary care providers delivered by Health Coaches to persons with dementia and caregiver "dyads" and supervised by an interdisciplinary team. SETTING: Home- and virtual-based dyad support. PARTICIPANTS: Persons with mild cognitive impairment or dementia diagnosis and/or who were prescribed antidementia medications; had an identified caregiver willing to participate; were under the care of a partner primary care provider; and had health insurance through the affiliated accountable care organization (Banner Health Network). INTERVENTION: Provision of personalized dementia education and support in the home or virtually by Health Coaches supported by an interdisciplinary team. MEASUREMENTS: Cognition, function, mood, and behavior of persons with dementia; caregiver stress and program satisfaction; primary care provider satisfaction. RESULTS: Served dyads from three primary care clinics with a total of 87 dyads enrolled between December 2018 and June 2020. CONCLUSION: A pilot Dementia Care Partners demonstrated feasibility and suggested acceptability, and high satisfaction among primary care providers and caregivers.

Healthy People and Interested Students: Medical and Pharmacy Students' Knowledge and Attitudes Regarding Public Health.

Little is known about health professions students' awareness and attitudes regarding public health in the United States. Therefore, the purpose of this study was to assess medical and pharmacy students' knowledge and interest in the Healthy People initiative as well as perceptions of public health content in their curricula. An electronic survey was distributed in March 2021 in seven schools across Ohio; participation was incentivized through a USD 5 donation to the Ohio Association of Foodbanks to aid in COVID-19 relief efforts (maximum USD 1000) for each completed survey. A total of 182 medical students and 233 pharmacy students participated (12% response rate). Less than one-third of respondents reported familiarity with Healthy People and correctly identified the latest edition. However, nearly all respondents agreed public health initiatives are valuable to the American healthcare system. Almost all students expressed a desire to practice interprofessionally to attain public health goals. Both medical and pharmacy students recognized core public health topics in their curricula, and nearly 90% wanted more information. These findings indicate that the majority of medical and pharmacy students in Ohio believe public health initiatives to be important, yet knowledge gaps exist regarding Healthy People. This information can guide curricular efforts and inform future studies of health professions students.

Measuring Apathy in Alzheimer's Disease in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): A Comparison of Instruments.

BACKGROUND: Diagnostic criteria for apathy have been published but have yet to be evaluated in the context of clinical trials. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) operationalized the diagnostic criteria for apathy (DCA) into a clinician-rated questionnaire informed by interviews with the patient and caregiver. OBJECTIVE: The goal of the present study was to compare the classification of apathy using the DCA with that using the Neuropsychiatric Inventory-apathy (NPI-apathy) subscale in ADMET 2. Comparisons between NPI-Apathy and Dementia Apathy Interview Rating (DAIR) scale, and DCA and DAIR were also explored. METHODS: ADMET 2 is a randomized, double-blind, placebo-controlled phase III trial examining the effects of 20 mg/day methylphenidate on symptoms of apathy over 6 months in patients with mild to moderate Alzheimer's disease (AD). Participants scoring at least 4 on the NPI-Apathy were recruited. This analysis focuses on cross-sectional correlations between baseline apathy scale scores using cross-tabulation. RESULTS: Of 180 participants, the median age was 76.5 years and they were predominantly white (92.8%) and male (66.1%). The mean (±standard deviation) scores were 7.7 ± 2.4 on the NPI-apathy, and 1.9 ± 0.5 on the DAIR. Of those with NPI-defined apathy, 169 (93.9%, 95% confidence interval [CI] 89.3%-96.9%) met DCA diagnostic criteria. The DCA and DAIR overlapped on apathy diagnosis for 169 participants (93.9%, 95% CI 89.3%-96.9%). CONCLUSION: The measurements used for the assessment of apathy in patients with AD had a high degree of overlap with the DCA. The NPI-apathy cut-off used to determine apathy in ADMET 2 selects those likely to meet DCA criteria.

Health Outcomes Associated with Adherence to Antidepressant Use during Acute and Continuation Phases of Depression Treatment among Older Adults with Dementia and Major Depressive Disorder.

OBJECTIVES: To examine health outcomes associated with adherence to Healthcare Effectiveness Data and Information Set (HEDIS) antidepressant medication management (AMM) during acute and continuation phases of depression treatment among older adults with dementia and major depressive disorder (MDD). DESIGN: Retrospective cohort study. SETTING: Medicare 5% sample data (2011-2013). PARTICIPANTS: Older adults (aged 65 years or older) with dementia and MDD. MEASUREMENTS: The first antidepressant prescription claim from 1 May 2011 through 30 April 2012 was considered the index prescription start date (IPSD). Adherence during acute- and continuation-phase AMM was based on HEDIS guidelines. Study outcomes included all-cause mortality, all-cause hospitalization, and falls/factures (with mortality being the competing event for hospitalization and falls/fractures) during follow-up from end of acute-/continuation-phase AMM adherence. Due to the proportionality assumption violation of Cox models, fully non-parametric approaches (Kaplan-Meier and modified Gray's test) were used for time-to-event analysis adjusting for the inverse probability of treatment weights. RESULTS: Final study samples consisted of 4330 (adherent (N) = 3114 (71.92%)) and 3941 (adherent (N) = 2407 (61.08%)) older adults with dementia and MDD during acute- and continuation-phase treatments, respectively. No significant difference (p > 0.05) between adherent and non-adherent groups was observed for all-cause mortality and falls/fractures in both the acute and continuation phases. There was a significant difference in time to all-cause hospitalization during acute-phase treatment (p = 0.018), with median times of 530 (95% CI: 499-587) and 425 (95% CI: 364-492) days for adherent and non-adherent groups, respectively. CONCLUSIONS: Acute-phase adherence to HEDIS AMM was associated with reductions in all-cause hospitalization risk among older adults with dementia and MDD.

Extent and Factors Associated with Adherence to Antidepressant Treatment During Acute and Continuation Phase Depression Treatment Among Older Adults with Dementia and Major Depressive Disorder.

PURPOSE: Little is known about adherence to antidepressant treatment during acute and continuation phase of depression among older adults with dementia and newly diagnosed major depressive disorders (MDD). This study estimated the extent of and factors associated with adherence to acute and continuation phase antidepressant treatment among older adults with dementia and newly diagnosed MDD. METHODS: We conducted a retrospective cohort study using the Medicare 5% sample claims data (2012-2013) among older adults (age≥65 years) with dementia who were newly diagnosed with MDD. Intake period of our study was from 01-May-2012 through 30-April-2013. The dependent variables of this study were acute and continuation phase depression treatment adherence. Factors associated with acute and continuation phase antidepressant treatment adherence were identified using multiple logistic regression analyses. RESULTS: The final study sample consisted of 6239 [adherent: N=4644 (74.44%)] and 5617 [adherent: N=3584 (63.81%)] older adults with dementia and MDD during the acute and continuation phase treatment, respectively. During the acute phase, only race/ethnicity was significantly associated with adherence to depression treatment, whereas race/ethnicity and baseline antipsychotic use were significantly associated with adherence to depression treatment during the continuation phase. CONCLUSION: Approximately, 74% and 64% older adults with dementia and MDD were adherent to acute and continuation phase antidepressant treatment in this nationally representative sample of Medicare beneficiaries, and we identified several modifiable and non-modifiable factors associated with adherence.

Machine learning models to predict onset of dementia: A label learning approach.

INTRODUCTION: The study objective was to build a machine learning model to predict incident mild cognitive impairment, Alzheimer's Disease, and related dementias from structured data using administrative and electronic health record sources. METHODS: A cohort of patients (n = 121,907) and controls (n = 5,307,045) was created for modeling using data within 2 years of patient's incident diagnosis date. Additional cohorts 3-8 years removed from index data are used for prediction. Training cohorts were matched on age, gender, index year, and utilization, and fit with a gradient boosting machine, lightGBM. RESULTS: Incident 2-year model quality on a held-out test set had a sensitivity of 47% and area-under-the-curve of 87%. In the 3-year model, the learned labels achieved 24% (71%), which dropped to 15% (72%) in year 8. DISCUSSION: The ability of the model to discriminate incident cases of dementia implies that it can be a worthwhile tool to screen patients for trial recruitment and patient management.

Understanding fertilizer adoption and effectiveness on maize in Zambia.

Increased fertilizer use will likely be crucial for raising and sustaining farm productivity in Africa, but adoption may be limited by ineffectiveness under certain conditions. This article quantifies the impacts of soil characteristics on maize response to fertilizer in Zambia using a nationally representative sample of 1453 fields, combining economic, farm management and soil analysis data. Depending on soil regimes, average maize yield response estimates range from insignificant (0) to 7 maize kg per fertilizer kg. For the majority of farmers, the estimated average value cost ratio is between 1 and 2, meaning fertilizer use would be fiscally rational, barring uncertainty and transfer costs. Since transfer costs exist and outcomes are uncertain, however, many farmers may sensibly pause before deciding whether to adopt fertilizer. This suggests shifting the emphasis of chronically low fertilizer use in Africa away from explanations of "market failure" toward greater emphasis on improving fertilizer efficacy.

Alzheimer's disease medication and risk of all-cause mortality and all-cause hospitalization: A retrospective cohort study.

INTRODUCTION: Identifying Alzheimer's disease (AD) pharmacologic treatment options that effectively reduce the risk of mortality and hospitalization in real-world settings is critical. METHODS: We compared donepezil, galantamine, memantine, oral rivastigmine, and transdermal rivastigmine with regard to all-cause mortality and all-cause hospitalization risk among fee-for-service Medicare beneficiaries with AD (aged ≥ 65 years) using a retrospective cohort study design. Our primary analysis was based on intention to treat (ITT), but we also present as-treated analysis. RESULTS: In our final study sample (N = 21,558), significant difference in survival among index AD medication groups were observed with donepezil being associated with better survival than memantine, and oral and transdermal forms of rivastigmine for both ITT and as-treated analysis. Difference in hazards of all-cause hospitalization among index AD medication groups was observed in ITT analysis but not in as-treated analysis. DISCUSSION: Significant differences exist in terms of mortality and hospitalization risk with different AD medication initiation in real-world setting.

Extent and Predictors of Potentially Inappropriate Antidepressant Use Among Older Adults With Dementia and Major Depressive Disorder.

OBJECTIVE: To quantify the extent and identify predictors of potentially inappropriate antidepressant use among older adults with dementia and newly diagnosed major depressive disorders (MDD). METHODS: This retrospective cohort study included older adults (aged ≥65 years) with dementia and newly diagnosed MDD using Medicare 5% sample claims data (2012-2013). Based on Healthcare Effectiveness Data and Information Set guidelines, intake period for new antidepressant medication use was from May 1, 2012, through April 30, 2013. Index prescription start date was the first date of antidepressant prescription claim during the intake period. Dependent variable of this study was potentially inappropriate antidepressant use as defined by the Beers Criteria and the Screening Tool of Older Persons' potentially inappropriate Prescriptions criteria. The authors conducted multiple logistic regression analysis to identify individual-level predictors of potentially inappropriate antidepressant use. RESULTS: The authors' final study sample consisted of 7,625 older adults with dementia and newly diagnosed MDD, among which 7.59% (N = 579) initiated treatment with a potentially inappropriate antidepressant. Paroxetine (N = 394) was the most commonly initiated potentially inappropriate antidepressant followed by amitriptyline (N = 104), nortriptyline (N = 35), and doxepin (N = 32). Initiation of a potentially inappropriate antidepressant was associated with age and baseline use of anxiolytic medications. CONCLUSION: More than 7% of older adults in the study sample initiated a potentially inappropriate antidepressant, and the authors identified a few individual-level factors significantly associated with it. Appropriately tailored interventions to address modifiable and nonmodifiable factors significantly associated with potentially inappropriate antidepressant prescribing are required to minimize risks in this vulnerable population.

Aldehyde adducts inhibit 3,4-dihydroxyphenylacetaldehyde-induced α-synuclein aggregation and toxicity: Implication for Parkinson neuroprotective therapy.

3,4-Dihydroxyphenylacetaldehyde (DOPAL), the monoamine oxidase (MAO) metabolite of dopamine, plays a role in pathogenesis of Parkinson disease, inducing α-synuclein aggregation. DOPAL generates discrete α-synuclein aggregates. Inhibiting this aggregation could provide therapy for slowing Parkinson disease progression. Primary and secondary amines form adducts with aldehydes. Rasagiline and aminoindan contain these amine groups. DOPAL-induced α-synuclein aggregates were resolved in the presence and absence of rasagiline or aminoindan using quantitative Western blotting. DOPAL levels in incubation mixtures, containing increased rasagiline or aminoindan concentrations, were determined by high pressure liquid chromatography (HPLC). Schiff base adducts between DOPAL and rasagiline or aminoindan were determined using mass spectrometry. A neuroprotective effect of rasagiline and aminoindan against DOPAL-induced toxicity was demonstrated using PC-12 cells. Rasagiline and aminoindan significantly reduced aggregation of α-synuclein of all sizes in test tube and PC-12 cells experiments. Dimethylaminoindan did not reduce aggregation. DOPAL levels in incubation mixtures were reduced with increasing rasagiline or aminoindan concentrations but not with dimethylaminoindan. Schiff base adducts between DOPAL and either rasagiline or aminoindan were demonstrated by mass spectrometry. A neuroprotective effect against DOPAL-induced toxicity in PC-12 cells was demonstrated for both rasagiline and aminoindan. Inhibiting DOPAL-induced α-synuclein aggregation through amine adducts provides a therapeutic approach for slowing Parkinson disease progression.

Identification of Baseline Characteristics Associated With Development of Depression Among Patients With Head and Neck Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Patients with head and neck cancer (HNC) experience increased risk of depression and compromised quality of life. Identifying patients with HNC at risk of depression can help establish targeted interventions. Objective: To identify factors that may be associated with the development of moderate or severe depression during treatment of HNC. Design, Setting, and Participants: This is a retrospective, ad hoc, secondary analysis of prospectively collected data from a randomized, double-blind, placebo-controlled clinical trial. Patients were screened at academic- and community-based tertiary care HNC centers from January 2008 to December 2011. Of the 125 evaluable patients with stages II through IV HNC but without baseline depression, 60 were randomized to prophylactic antidepressant escitalopram oxalate and 65 to placebo at the time of the initial diagnosis. Data analyses were conducted from May 2016 to April 2017. Main Outcomes and Measures: Depression outcomes were measured using Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) scores (range, 0-27 with a score of 11 or higher indicative of moderate or greater depression). Factors that may be associated with development of moderate or severe depression were assessed, including patient demographics; cancer site and stage; primary treatment modality (surgery or radiotherapy); history of depression or other psychiatric diagnosis; previous treatment of depression or suicide attempt, family history of depression, suicide, or suicide attempt; and baseline score on the QIDS-SR and clinician-rated QIDS instruments. Participants were stratified by study site, sex, cancer stage (early [stage II] vs advanced [stage III or IV]), primary modality of treatment (radiotherapy with or without chemotherapy vs surgery with or without radiotherapy), and randomization to placebo or escitalopram and balanced within these strata. Results: The mean (SD) age of the 148 patients in the study population was 63.0 (11.9) years; 118 (79.7%) were men, and 143 (96.6%) were white. In the evaluable population of 125 patients, receiver operating characteristic analyses assessing the area under the curve for baseline QIDS-SR score (0.816; 95% CI, 0.696-0.935) and for initial radiotherapy-based treatment (0.681, 95% CI, 0.552-0.811) suggested that these 2 variables were associated with the likelihood of developing moderate or greater depression during the study period among patients who did not receive prophylactic antidepressants. The diagnostic sensitivity for identifying patients at risk of depression using the baseline QIDS-SR score improved to 100% at a threshold of 2 from 94% at a threshold of 4. Conclusions and Relevance: Baseline symptoms and initial radiotherapy-based treatment may be associated with development of moderate or greater depression in patients with HNC. Patients with QIDS-SR baseline scores of 2 or higher may benefit the most from pharmacologic prophylaxis of depression.

Depression Screening Patterns, Predictors, and Trends Among Adults Without a Depression Diagnosis in Ambulatory Settings in the United States.

OBJECTIVE: This study examined national patterns, predictors, and trends in depression screening among adults without a diagnosis of depression in the United States. METHODS: A cross-sectional design utilizing pooled data from the National Ambulatory Medical Care Survey (2005-2015) was used. The study sample consisted of ambulatory care visits to nonpsychiatrists among adults (≥18 years) without a depression diagnosis. Depression screening was the dependent variable. Descriptive statistics, logistic regression, and piecewise regression analyses were conducted to achieve the study objectives. RESULTS: The national-level depression screening rate was 1.4% of all adult ambulatory care visits. Year, gender, physician specialty, geographic region, and time spent with physician were significantly associated with depression screening. Piecewise regression analysis revealed a statistically significant (p<.001) interaction between year and change in depression screening rate, where screening rates increased significantly after 2009. CONCLUSIONS: Although screening rates have increased significantly after 2009, screening remains low among adults without a depression diagnosis.

Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Apathy is a common behavioral problem in Alzheimer's disease. Apathy has profound consequences, such as functional impairment, higher service utilization, higher caregiver burden, and increased mortality. The authors' objective was to study the effects of methylphenidate on apathy in Alzheimer's disease. METHOD: A 12-week, prospective, double-blind, randomized, placebo-controlled trial (methylphenidate versus placebo) was conducted in community-dwelling veterans (N=60) with mild Alzheimer's disease. The primary outcome for apathy (Apathy Evaluation Scale-Clinician) and secondary outcomes for cognition (Mini-Mental State Examination, Modified Mini-Mental State Examination), functional status (activities of daily living, instrumental activities of daily living), improvement and severity (Clinical Global Impressions Scale [CGI]), caregiver burden (Zarit Burden Scale), and depression (Cornell Scale for Depression in Dementia) were measured at baseline and at 4, 8, and 12 weeks. RESULTS: Participants were all men (77 years old, SD=8). After adjusting for baseline, the methylphenidate group had significantly greater improvement in apathy than the placebo group at 4 weeks, 8 weeks, and 12 weeks. At 12 weeks, there was also greater improvement in cognition, functional status, caregiver burden, CGI scores, and depression in the methylphenidate group compared with the placebo group. CONCLUSIONS: Methylphenidate improved apathy in a group of community-dwelling veterans with mild Alzheimer's disease. Methylphenidate also improved cognition, functional status, caregiver burden, CGI scores, and depression.

Prevalence, Patterns, and Predictors of Depression Treatment among Community-Dwelling Elderly Individuals with Dementia in the United States.

OBJECTIVES: Co-occurring dementia and depression exerts a substantial burden on the elderly. This study utilizes data from a nationally representative cohort of community-dwelling individuals 65 years and older to examine the prevalence, patterns, and predictors of depression treatment among elderly individuals with co-occurring dementia and depression. DESIGN: Retrospective, cross-sectional study. SETTING: Multiple years of Medical Expenditure Panel Survey (2002, 2004, 2006, 2008, 2010, and 2012) data. PARTICIPANTS: The study sample consisted of elderly (age ≥65 years) individuals who 1) had dementia, 2) were alive during the calendar year, and 3) had co-occurring depression. MEASUREMENTS: The dependent variable of this study was depression treatment, identified by antidepressant medication with or without psychotherapy use. Individual level factors associated with depression treatment among elderly individuals with dementia and co-occurring depression were evaluated by conducting multinomial logistic regression. RESULTS: Co-occurring depression prevalence among community-dwelling elderly individuals with dementia was approximately 22%. An overwhelming majority (nearly 88%) of the study sample reported receipt of depression treatment. Antidepressants only and combination therapy (antidepressant with psychotherapy) was reported by 75% and 13%, respectively, of the study sample. Age, race/ethnicity, marital status, limitations of instrumental activities of daily living, perceived mental health status, and pain were significantly associated with the reporting of receipt of depression treatment. CONCLUSIONS: An overwhelming majority of the study sample received depression treatment and several subgroup differences (such as in terms of age) existed in terms of reporting the use of depression treatment was observed.