Pittsburgh Sleep Quality Index (PSQI) responses are modulated by total sleep time and wake after sleep onset in healthy older adults.

OBJECTIVES: To investigate the objective sleep influencers behind older adult responses to subjective sleep measures, in this case, the Pittsburgh Sleep Quality Index (PSQI). Based on previous literature, we hypothesized that SE would be associated with PSQI reported sleep disruption. Furthermore, because SOL increases progressively with age and it tends to be easily remembered by the patients, we also expected it to be one of the main predictors of the perceived sleep quality in the elderly. METHODS: We studied 32 cognitively healthy community-dwelling older adults (age 74 ± 0.3 years) who completed an at-home sleep assessment (Zeo, Inc.) and the PSQI. Linear mixed models were used to analyze the association of the objective sleep parameters (measured by the Zeo) with the PSQI total score and sub-scores, adjusting for age, gender, years of education and likelihood of sleep apnea. RESULTS: Objective sleep parameters did not show any association with the PSQI total score. We found that objective measures of Wake after sleep onset (WASO, % and min) were positively associated with the PSQI sleep disturbance component, while SE and Total Sleep Time (TST) were negatively associated with PSQI sleep disturbance. Lastly, objective SE was positively associated with PSQI SE. CONCLUSIONS: Our findings showed that WASO, SE and TST, are associated with PSQI sleep disturbance, where the greater WASO, overall lower SE and less TST, were associated with increased subjective report of sleep disturbance. As expected, subjective (PSQI) and objective measures of SE were related. However, PSQI total score did not relate to any of the objective measures. These results suggest that by focusing on the PSQI total score we may miss the insight this easily administered self-report tool can provide. If interpreted in the right way, the PSQI can provide further insight into cognitively healthy older adults that have the likelihood of objective sleep disturbance.

Specific cortical and subcortical grey matter regions are associated with insomnia severity.

BACKGROUND: There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen. METHODS: 120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed. RESULTS: ISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (p<0.001, uncorrected FWE). When adjusting by GDS, right ventral orbitofrontal and temporo-parietal junction remained significant, and left insula became significant (p<0.001, uncorrected FWE). Conversely, BA showed no effect. The results were no longer significant following FWE multiple comparisons. Regarding subcortical areas, higher putamen volumes were associated with higher ISI (p<0.01). CONCLUSIONS: Our findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia.

In vivo Mouse Model of Spinal Implant Infection.

Spine implant infections portend poor outcomes as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. The purpose of this method is to describe a novel mouse model of spinal implant infection (SII) that was created to provide an inexpensive, rapid, and accurate in vivo tool to test potential therapeutics and treatment strategies for spinal implant infections. In this method, we present a model of posterior-approach spinal surgery in which a stainless-steel k-wire is transfixed into the L4 spinous process of 12-week old C57BL/6J wild-type mice and inoculated with 1 x 103 CFU of a bioluminescent strain of Staphylococcus aureus Xen36 bacteria. Mice are then longitudinally imaged for bioluminescence in vivo on post-operative days 0, 1, 3, 5, 7, 10, 14, 18, 21, 25, 28, and 35. Bioluminescence imaging (BLI) signals from a standardized field of view are quantified to measure in vivo bacterial burden. To quantify bacteria adhering to implants and peri-implant tissue, mice are euthanized and the implant and surrounding soft tissue are harvested. Bacteria are detached from the implant by sonication, cultured overnight and then colony forming units (CFUs) are counted. The results acquired from this method include longitudinal bacterial counts as measured by in vivo S. aureus bioluminescence (mean maximum flux) and CFU counts following euthanasia. While prior animal models of instrumented spine infection have involved invasive, ex vivo tissue analysis, the mouse model of SII presented in this paper leverages noninvasive, real time in vivo optical imaging of bioluminescent bacteria to replace static tissue study. Applications of the model are broad and may include utilizing alternative bioluminescent bacterial strains, incorporating other types of genetically engineered mice to contemporaneously study host immune response, and evaluating current or investigating new diagnostic and therapeutic modalities such as antibiotics or implant coatings.

A systematic overview of systematic reviews evaluating medication adherence interventions.

PURPOSE: To systematically summarize evidence from multiple systematic reviews (SRs) examining interventions addressing medication nonadherence and to discern differences in effectiveness by intervention, patient, and study characteristics. SUMMARY: MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects were searched for papers published from January 2004 to February 2017. English-language SRs examining benefits of medication adherence interventions were eligible. Inclusion was limited to adult patients prescribed medication for 1 of the following disease conditions: diabetes and prediabetes, heart conditions, hypertension and prehypertension, stroke, and cognitive impairment. Non-disease-specific SRs that considered medication adherence interventions for older adults, adults with chronic illness, and adults with known medication adherence problems were also included. Two researchers independently screened titles, abstracts, and full-text articles. They then extracted key variables from eligible SRs, reconciling discrepancies via discussion. A MeaSurement Tool to Assess systematic Reviews (AMSTAR) was used to assess SRs; those with scores below 8 were excluded. Conclusions regarding intervention effectiveness were extracted. Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was applied to assess evidence quality. RESULTS: Of 390 SRs, 25 met the inclusion criteria and assessed adherence as a primary outcome. Intervention types most consistently found to be effective were dose simplification, patient education, electronic reminders to patients, and reduced patient cost sharing or incentives. Of 50 conclusions drawn by the SRs, the underlying evidence was low or very low quality for 45 SRs. CONCLUSION: Despite an abundance of primary studies and despite only examining high-quality SRs, the vast majority of primary studies supporting SR authors' conclusions were of low or very low quality. Nonetheless, health system leaders seeking to improve medication adherence should prioritize interventions that have been studied and found to be effective at improving patient adherence, including dose simplification, education, reminders, and financial incentives.

Effect of medication reconciliation interventions on outcomes: A systematic overview of systematic reviews.

PURPOSE: To evaluate and summarize published evidence from systematic reviews examining medication reconciliation. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects were searched for English-language systematic reviews published from January 2004 to March 2019. Reviewers independently extracted information and scored review quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. For reviews with AMSTAR scores above 7, Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess evidence quality, with evidence summarized and conclusions compared across reviews. RESULTS: Eleven reviews met the inclusion criteria, 5 of which used meta-analytic pooling. Most systematic reviews included primary studies of comprehensive bundled interventions that featured medication reconciliation as a central component. Reviews largely focused on transitions into and out of hospital settings. Five reviews focused exclusively on pharmacist-led interventions. Of the 5 reviews that considered all types of medication discrepancies, 3 reviews found very low-quality evidence that interventions reduced medication discrepancies. Neither of the 2 reviews that examined clinically significant medication discrepancies found any intervention effect. Of the 5 reviews that examined healthcare utilization outcomes, only 1 found any intervention effect, and that finding was based on low- to very low-quality evidence. Four reviews considered clinical outcomes, but none found any intervention effect. CONCLUSION: An overview of systematic reviews of medication reconciliation interventions found 9 high-quality systematic reviews. A minority of those reviews' conclusions were consistent with medication reconciliation alone having a measurable impact, and such conclusions were almost all based on very low-quality evidence.

A systematic overview of systematic reviews evaluating interventions addressing polypharmacy.

PURPOSE: To systematically evaluate and summarize evidence across multiple systematic reviews (SRs) examining interventions addressing polypharmacy. SUMMARY: MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (DARE) were searched for SRs evaluating interventions addressing polypharmacy in adults published from January 2004 to February 2017. Two authors independently screened, appraised, and extracted information. SRs with Assessment of Multiple Systematic Reviews (AMSTAR) scores below 8 were excluded. After extraction of relevant conclusions from each SR, evidence was summarized and conclusions compared. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess evidence quality. Six SRs met the inclusion criteria, 4 of which used meta-analytic pooling. Five SRs focused on older adults. Four were not restricted to any specific disease type, whereas 1 focused on proton pump inhibitors and another focused on patients with severe dementia. Care settings and measured outcomes varied widely. SRs examining the impact on patient-centered outcomes, including morbidity, mortality, patient satisfaction, and utilization, found inconsistent evidence regarding the benefit of polypharmacy interventions, but most concluded that interventions had either null or uncertain impact. Two SRs assessing medication appropriateness found very low-quality evidence of modest improvements with polypharmacy interventions. CONCLUSION: An overview of SRs of interventions to address polypharmacy found 6 recent and high-quality SRs, mostly focused on older adults, in which both process and outcome measures were used to evaluate interventions. Despite the low quality of evidence in the underlying primary studies, both SRs that assessed medication appropriateness found evidence that polypharmacy interventions improved it. However, there was no consistent evidence of any impact on downstream patient-centered outcomes such as healthcare utilization, morbidity, or mortality.