Timed Activity to Minimize Sleep Disturbance in People With Cognitive Impairment.

Background and Objectives: Sleep disturbances occur in >60% of persons living with cognitive impairment, affecting their quality of life (QOL). Regulating the sleep-wake cycle through engaging cognitive, physical, and sensory-based activities delivered at strategic times may reduce sleep disturbances and be a feasible nonpharmacological treatment for sleep problems. The objective of this trial was to test the efficacy of a timed-activity intervention in improving QOL and sleep disturbances in persons living with cognitive impairment. Research Design and Method: Randomized 2-group parallel design involving 209 dyads of community-residing persons living with cognitive impairment and care partners. Dyads were randomly assigned (1:1) to 1-hr home activity sessions administered weekly in the morning, afternoon, or evening over 4 weeks (the Healthy Patterns Sleep Program), or to an attention-control condition consisting of sleep hygiene training plus education on home safety and health promotion. QOL, objective and subjective sleep quality, and neuropsychiatric symptoms were assessed at baseline and 4 weeks later. Results: QOL was significantly improved in the intervention group compared to control (p = .0491). There were no significant effects on objective or subjective sleep or neuropsychiatric symptoms. In a subgroup analysis, subjective sleep as measured by the PROMIS (Patient Reported Outcomes Measurement Information System) Sleep-Related Impairment survey was significantly improved in the intervention group compared to the control group for individuals with symptoms of depression (p = .015) or poor observed sleep at baseline (p = .005). Discussion and Implications: The Healthy Patterns Intervention may benefit QOL for persons living with cognitive impairment and those with poor subjective sleep. A longer dose may be necessary to elicit improvement in actigraphically measured sleep-wake activity. Clinical Trial Registration Number: NCT0368218 5.

Feasibility and acceptability of a web-based advance care plan for dementia.

While advance care planning (ACP) can help elicit preferences and is associated with improved end-of-life outcomes, persons living with dementia (PLWD) in nursing homes are rarely included in ACP. Web-based decision aids are a readily available tool to engage PLWD in ACP, but none are designed for the unique needs of PLWD, particularly those residing in nursing homes. Our Memory Care Wishes (OMCW) was adapted from a publicly available web-based ACP tool in collaboration with dementia care experts. This study aimed to explore the acceptability of OMCW. We used a convergent, mixed methods design to describe PLWD and surrogates' experiences using the OMCW website. Participants described ease of use, comfort with viewing, helpfulness for planning, and likelihood to recommend. Overall, OMCW is acceptable, however, PLWD continue to have difficulties understanding and engaging with some website content. Modifications were incorporated based on these findings, setting the stage for implementation and effectiveness testing.

The Relationship Between Light Exposure before Bedtime and Daytime Sleepiness Among People Living With Cognitive Impairment.

While sleep disturbances are common in people living with cognitive impairment, little is known about the influence of evening light exposure on their sleep. The purpose of this study was to examine the relationship between evening light exposure in natural living environment and daytime sleepiness in community residing people living with cognitive impairment. A secondary data analysis was conducted using the baseline data of the Healthy Patterns Clinical Trial. Actiwatch Spectrum Plus was used to collect information on the average white light intensity of 4 hours before sleep for three consecutive days. Multivariate regression analyses were used. Among 173 participants, the average light intensity during evening was 80.25 ± 123.04 lux. After controlling for covariates, greater intensity of light exposure during evening was related to excessive daytime sleepiness (ß = 0.211, p = .004). The results of our study suggest exposure to light during evening may disturb sleep and subsequently influence daytime sleepiness the following day.

A timed activity protocol to address sleep-wake disorders in home dwelling persons living with dementia: the healthy patterns clinical trial.

BACKGROUND: Sleep-wake disorders occur in most persons living with dementia and include late afternoon or evening agitation, irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, and poor sleep efficiency. Sleep-wake disorders pose a great burden to family caregivers, and are the principal causes of distress, poor quality of life, and institutionalization. Regulating the sleep-wake cycle through the use of light and activity has been shown to alter core clock processes and suggests that a combination of cognitive, physical, and sensory-based activities, delivered at strategic times, may be an effective mechanism through which to reduce sleep-wake disorders. METHODS: A definitive Phase III efficacy trial of the Healthy Patterns intervention, a home-based activity intervention designed to improve sleep-wake disorders and quality of life, is being conducted using a randomized two-group parallel design of 200 people living with dementia and their caregivers (dyads). Specific components of this one-month, home-based intervention involve 4 in-home visits and includes: 1) assessing individuals' functional status and interests; 2) educating caregivers on environmental cues to promote activity and sleep; and 3) training caregivers in using timed morning, afternoon, and evening activities based on circadian needs across the day. The patient focused outcomes of interest are quality of life, measures of sleep assessed by objective and subjective indicators including actigraphy, subjective sleep quality, and the presence of neuropsychiatric symptoms. Caregiver outcomes of interest are quality of life, burden, confidence using activities, and sleep disruption. Salivary measures of cortisol and melatonin are collected to assess potential intervention mechanisms. DISCUSSION: The results from the ongoing study will provide fundamental new knowledge regarding the effects of timing activity participation based on diurnal needs and the mechanisms underlying timed interventions which can lead to a structured, replicable treatment protocol for use with this growing population of persons living with dementia. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov # NCT03682185 at https://clinicaltrials.gov/ ; Date of clinical trial registration: 24 September 2018.

Caveat emptor: Erroneous safety information about opioids in online drug-information compendia.

BACKGROUND: Healthcare professionals and consumers refer to online drug-information compendia (eg, Epocrates and WebMD) to learn about prescription medications, including opioid analgesics. With the significant risks associated with opioids, including abuse, misuse, and addiction, any of which can result in life-threatening overdose, it is important for those seeking information from online compendia to have access to current, accurate, and complete drug information to help support clinical treatment decisions. Although compendia are informative, readily available, and user friendly, studies have shown that they may contain errors. OBJECTIVE: To review and identify misinformation in drug summaries of online drug-information compendia for selected opioid analgesic products and submit content corrections to the respective editors. METHODS: Between 2011 and 2013, drug summaries for Purdue's prescription opioid analgesic products from seven leading online drug-information compendia were systematically reviewed, and the requests for corrections were retrospectively categorized and classified. At least 2 months following requests, the same compendia were then reexamined to assess the degree of error resolution. RESULTS: A total of 859 errors were identified, with the greatest percentage in Safety and Patient Education categories. Across the seven compendia, the complete or partial resolution of errors was 34 percent; therefore, nearly two thirds of the identified errors remain. CONCLUSION: The results of this analysis, consistent with past studies, demonstrate that online drug-information compendia may contain inaccurate information. Healthcare professionals and consumers must be informed of potential misinformation so they may consider using multiple resources to obtain accurate and current drug information, thereby helping to ensure safer use of prescription medications, such as opioids.

Implementing a Process to Review Product-Specific Misinformation in Online Drug Information Compendia.

Health care professionals and consumers often use online drug information compendia, which are intended to be user-friendly, readily available, accurate, and up-to-date. While these resources can be valuable, it has been shown that some compendia contain inaccuracies and outdated information, motivating the Medical Services (medical information) Department at Purdue Pharma LP to implement a periodic, standardized review of select online drug information compendia. Monographs within compendia for up to 9 Purdue products were reviewed and compared to their current Full Prescribing Information, with a focus on identifying safety-related misinformation. Content correction requests for nearly 1000 errors were submitted to 7 compendia clinical editors. This surprisingly large number of errors highlights the need for compendia to better maintain accurate product monographs, as well as for pharmaceutical companies to proactively and periodically review them for misinformation. Based on these findings, an overview on how the pharmaceutical industry may implement a drug information compendia review process is provided.

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration.

BACKGROUND: Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [25(OH)D] concentration >75 nmol/L. OBJECTIVE: We aimed to determine the intake of vitamin D(3) needed to raise serum 25(OH)D to >75 nmol/L. DESIGN: The design was a 6-mo, prospective, randomized, double-blinded, double-dummy, placebo-controlled study of vitamin D(3) supplementation. Serum 25(OH)D was measured by radioimmunoassay. Vitamin D(3) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration. RESULTS: A total of 138 subjects entered the study. After 2 dose adjustments, almost all active subjects attained concentrations of 25(OH)D >75 nmol/L, and no subjects exceeded 220 nmol/L. The mean (+/-SD) slope at 9 wk [defined as 25(OH)D change/baseline dose] was 0.66 +/- 0.35 (nmol/L)/(microg/d) and did not differ statistically between blacks and whites. The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.

Dose response to vitamin D supplementation among postmenopausal African American women.

BACKGROUND: Reports on the dose response to vitamin D are conflicting, and most data were derived from white men and women. OBJECTIVE: The objective was to determine the response of serum 25-hydroxyvitamin D [25(OH)D] to oral vitamin D(3) supplementation in an African American population. DESIGN: Healthy black postmenopausal women (n = 208) participated in a vitamin D(3) supplementation trial for a period of 3 y. Analyses were done in the vitamin D supplementation arm (n = 104) to quantify the response in serum 25-hydroxyvitamin D concentrations at a steady state vitamin D input. The participants received 20 microg/d (800 IU) oral vitamin D(3) for the initial 2 y and 50 microg/d (2000 IU) for the third year. RESULTS: Supplementation with 20 microg/d (800 IU/d) vitamin D(3) raised the mean serum 25(OH)D concentration from a baseline of 46.9 +/- 20.6 nmol/L to 71.4 +/- 21.5 nmol/L at 3 mo. The mean (+/-SD) concentration of serum 25(OH)D was 87.3 +/- 27.0 nmol/L 3 mo after supplementation increased to 50 microg/d (2000 IU/d). All participants achieved a serum 25(OH)D concentration >35 nmol/L, 95% achieved a concentration >50 nmol/L, but only 60% achieved a concentration >75 nmol/L. All patients had concentrations <153 nmol/L. On the basis of our findings, an algorithm for prescribing vitamin D so that patients reach optimal serum concentrations was developed. The algorithm suggests a dose of 70 microg (2800 IU/d) for those with a concentration >45 nmol/L and a dose of 100 microg (4000 IU/d) for those with a concentration <45 nmol/L. CONCLUSIONS: Supplementation with 50 microg/d (2000 IU/d) oral vitamin D(3) is sufficient to raise serum 25-hydroxyvitamin D concentrations to >50 nmol/L in almost all postmenopausal African American women. However, higher doses were needed to achieve concentrations >75 nmol/L in many women in this population.

Vitamin-D nutrition and bone mass in adolescent black girls.

OBJECTIVE: To examine the relationship between bone mass and serum levels of 25-hydroxyvitamin D and parathyroid hormone in African-American adolescent girls. STUDY DESIGN: A cross-sectional sample at a suburban research center. METHODS: Twenty-one adolescent black girls 12-14 years of age, were studied during winter with biochemical measurements of serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH). Bone mass assessment was done with dual energy x-ray absorbsiometry (DXA) and peripheral quantitative computed tomography of the radius (p-QCT). Anthropometric, physical activity and nutritional data were collected. RESULTS: All participants were vitamin-D deficient (serum 25-OHD level <50 nmol/L), of whom nine (43%) were severely vitamin-D deficient (serum 25-OHD level <20 nmol/L). Mean daily intake of dietary calcium was 540 mg/d and vitamin D was 195 IU/d. There was a positive correlation, although statistically not significant, between serum 25-OHD and various bone mass measurements. Serum PTH was inversely correlated to total body BMD (r = -0.51, p = 0.02) and other bone mineral density at the lumbar spine, total femur and mid-radius. CONCLUSION: Vitamin-D insufficiency is a widely prevalent problem among adolescent African-American girls. Our data implies that enhancing vitamin-D nutrition resulting in lower serum PTH levels could potentially influence their peak bone mass.

Optimal vitamin D status and serum parathyroid hormone concentrations in African American women.

BACKGROUND: Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). OBJECTIVE: The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. DESIGN: The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. RESULTS: A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. CONCLUSION: Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status.

A randomized controlled trial of vitamin D3 supplementation in African American women.

BACKGROUND: We conducted a randomized, placebo-controlled, double-blind trial to test the hypothesis that vitamin D(3) supplementation would prevent bone loss in calcium-replete, African American postmenopausal women. METHODS: Two hundred eight healthy black postmenopausal women, 50 to 75 years of age, were assigned to receive either placebo or 20 microg/d (800 IU) of vitamin D(3). Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d. After 2 years, the vitamin D(3) dose was increased to 50 microg/d (2000 IU) in the active group, and the study continued for an additional year. Bone mineral density (BMD) was measured every 6 months. Markers of bone turnover, vitamin D metabolites, and parathyroid hormone (PTH) levels were measured in serum. RESULTS: There were no significant differences in BMD between the active and control groups throughout the study. There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss. There was an increase in BMD of the total body, hip, and radius at 1 year in both groups. Over the 3 years, BMD declined at these sites by 0.26% to 0.55% per year. The BMD of the lumbar spine increased slightly in the placebo and active groups. There were no persistent changes in serum PTH levels or the markers of bone turnover, although there was a transient decline in PTH in both groups at 3 months. No significant adverse events were attributed to vitamin D supplementation. CONCLUSIONS: There was no observed effect of vitamin D(3) supplementation on bone loss or bone turnover markers in calcium-replete, postmenopausal African American women. Further studies are needed to determine if these findings are applicable to women of other ethnic groups.