Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

BACKGROUND: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown. OBJECTIVES: The study aimed to characterize the long-term effects of STN-deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts. METHODS: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN-LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular-resampling auto-spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN-LFP signals in beta band. RESULTS: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications. CONCLUSIONS: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society.

Older persons living with dementia and their use of acute care services over 2 years in Alberta.

OBJECTIVE: To characterize transitions to acute and residential care and identify variables associated with specific transitions among community-based persons living with dementia (PLWD). DESIGN: Retrospective cohort study using primary care electronic medical record data linked with health administrative data. SETTING: Alberta. PARTICIPANTS: Adults aged 65 years or older living in the community who had been diagnosed with dementia and who saw a Canadian Primary Care Sentinel Surveillance Network contributor between January 1, 2013, and February 28, 2015. MAIN OUTCOME MEASURES: All emergency department visits, hospitalizations, residential care (supportive living and long-term care) admissions, and deaths within a 2-year follow-up period. RESULTS: In total, 576 PLWD were identified who had a mean (SD) age of 80.4 (7.7) years; 55% were female. In 2 years, 423 (73.4%) had at least 1 transition and, of these, 111 (26.2%) had 6 or more. Emergency department visits, including multiple visits, were common (71.4% had ≥1, 12.1% had ≥4). Of those hospitalized (43.8%), nearly all were admitted from the emergency department; the average (SD) length of stay was 23.6 (35.8) days, and 32.9% had at least 1 alternate level of care day. In total, 19.3% entered residential care, most admitted from hospital. Those admitted to hospital and those admitted to residential care were older and had greater historical health system use, including home care. One-quarter of the sample did not have any transitions (or die) during follow-up; they were typically younger and had limited historical health system use. CONCLUSION: Older PLWD experienced frequent, and frequently compound, transitions that have implications for them, their family members, and the health system. There was also a large proportion without transitions suggesting that appropriate supports enable PLWD to do well in their own communities. The identification of PLWD who are at risk of or who make frequent transitions may allow for more proactive implementation of community-based supports and smoother transitions to residential care.

Epidemiology of dementia onset captured in Canadian primary care electronic medical records.

BACKGROUND: Dementia is an increasing concern in many countries, especially in those experiencing rapid growth in the proportion of older adults in their population. OBJECTIVE: This study aims to describe trends and demographic characteristics of incident dementia cases in community-dwelling older adults managed by primary care physicians. METHODS: We used electronic medical records from the Canadian Primary Care Sentinel Surveillance Network database to conduct a retrospective analysis to determine the number of, and trends for, incident diagnoses of dementia. Age-standardized annual incidence rates were calculated. Participants in our cohort are Canadian community dwelling seniors aged 65+ years who were not diagnosed with dementia before baseline with at least six years of record at their primary care clinics. RESULTS: The cohort consisted of 39 067 patients of whom 57% were females; the mean (SD) follow-up was 8.4 (1.5) years. During follow-up, 4935 patients were diagnosed with dementia. The risk for dementia diagnosis increased with increasing age but decreased in the last four years among people aged 80 and older at baseline (P < 0.001). People with dementia were more likely to be females (P = 0.001) and urban residents (P < 0.001), they are less likely to be classified into the least deprived group (P = 0.012). CONCLUSIONS: The incidence of dementia diagnosis increased with age except in the oldest old in both sexes. This may be attributed to the effect of mortality competing risk. Future research on the association between risk factors and dementia should consider studying dementia among the oldest old separately to minimize bias.

Dementias are conditions that may cause mental symptoms such as forgetfulness, confusion, or disorientation. As the population gradually ages, the number of dementia cases is also increasing. Among people aged 65 and over, the rate of dementia onset increases as people get older. However, among people aged 85 and over, the rate of developing dementia is slower, which might reflect that people who reach the age of 85 are usually healthier in general. Since family practitioners are normally the first contact when patients and their family notice symptoms, primary care plays an important role in diagnosing and managing dementia. Early recognizing dementia for early support is very helpful. According to our study, health-related information recorded in primary care in Canada is sufficient to be used for research. It is a valuable opportunity to study the characteristics of people with dementia, including their health conditions, risks and protective factors that may contribute to the development of the disease.

Risk factors for incidence of dementia in primary care practice: a retrospective cohort study in older adults.

BACKGROUND: The dementias are long-term, chronic conditions caused by progressive neurological degeneration. Current literature suggests that cardiovascular disease risk factors may contribute to the onset of dementia; however, evidence of these associations is inconsistent. OBJECTIVES: This study aimed to examine the impact of risk factors on dementia onset in older adults diagnosed and managed in Canadian primary care settings. METHODS: A retrospective cohort study was employed utilizing electronic medical records data in the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Patients aged 65+ years with no dementia diagnosis at baseline who were followed from 2009 to 2017 with a run-in year to exclude existing undiagnosed dementia cases. Multivariate Cox proportional hazard models were used to estimate risk. RESULTS: Age was associated with an increased incidence risk of dementia in both examined age groups: 65-79 years (13%) and 80+ years (5%). History of depression increased dementia risk by 38% and 34% in the age groups. There were significant associations with lower social deprivation area quintile, smoking history, osteoarthritis, and diabetes mellitus in patients aged 65-79 years but not in those aged 80+ years. Sex, hypertension, obesity, dyslipidemia, and the use of antihypertensive medications and statins were not associated with risk of incident dementia diagnosis. CONCLUSIONS: The association between chronic health conditions and dementia onset is complicated. Primary care electronic medical record data might be useful for research in this topic, though follow-up time is still relatively short to observe a clear causal relationship. Future studies with more complete data may provide evidence for dementia preventive strategies within primary care practice.

Fostering trust and sharing responsibility to increase access to dementia care for immigrant older adults.

Objectives: This paper explores the role of immigrant-serving agencies in facilitating access to dementia services and supports provided by dementia service agencies (particularly the health authority and local chapters of the Alzheimer Society) through their propensity to develop trusting relationships between staff and clients.Design: Our research is a qualitative case study of Punjabi and Korean speakers living in the Lower Mainland of BC, Canada. Data are drawn from interviews with 15 dyads of persons with dementia and their family caregivers (10 Punjabi, 5 Korean), six focus groups (one focus group with each of 8-10 older men, older women, and mixed gender working age adults in each community). We also interviewed 20 managerial and frontline staff of dementia service agencies, i.e. the health authority and the local Alzheimer Society (n = 11) and two immigrant-serving agencies (n = 9), each dedicated to either Punjabi or Korean-speaking clients. We adopted the Candidacy framework for understanding access to dementia services and supports and the concept of trust as guiding precepts in this study.Results: Families of persons with dementia are pivotal to identification of a problem requiring professional help, navigation to appropriate services and acceptance of services offered. However, trust in family members should not be taken for granted, since family dynamics are complex. Alternative sources of trusted support are therefore needed. Immigrant-serving agencies are more often instrumental in establishing trusted relationships between their staff and clients, but they often lack detailed knowledge about heath conditions, their treatment and management, and they lack power to implement statutory care.Conclusions: Partnerships between mainstream mental health/dementia services and the community sector have proven successful in increasing the accessibility of specialized resources, while maximizing their combined trustworthiness, accessibility and effectiveness. Such partnerships should become fundamental components of health service strategy and provision for vulnerable and underserved immigrant older adults.

Out-of-Plane Dielectric Susceptibility of Graphene in Twistronic and Bernal Bilayers.

We describe how the out-of-plane dielectric polarizability of monolayer graphene influences the electrostatics of bilayer graphene-both Bernal (BLG) and twisted (tBLG). We compare the polarizability value computed using density functional theory with the output from previously published experimental data on the electrostatically controlled interlayer asymmetry potential in BLG and data on the on-layer density distribution in tBLG. We show that monolayers in tBLG are described well by polarizability αexp = 10.8 Å3 and effective out-of-plane dielectric susceptibility ϵz = 2.5, including their on-layer electron density distribution at zero magnetic field and the interlayer Landau level pinning at quantizing magnetic fields.

Fronto-subthalamic phase synchronization and cross-frequency coupling during conflict processing.

Growing evidence suggests that both the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) play crucial roles in conflict processing, but how these two structures coordinate their activities remains poorly understood. We simultaneously recorded electroencephalogram from the mPFC and local field potentials from the STN using deep brain stimulation electrodes in 13 Parkinson's disease patients while they performed a Stroop task. Both mPFC and STN showed significant increases in theta activities (2-8 Hz) in incongruent trials compared to the congruent trials. The theta activity in incongruent trials also demonstrated significantly increased phase synchronization between mPFC and STN. Furthermore, the amplitude of gamma oscillation was modulated by the phase of theta activity at the STN in incongruent trials. Such theta-gamma phase-amplitude coupling (PAC) was much stronger for incongruent trials with faster reaction times than those with slower reaction times. Elevated theta-gamma PAC in the STN provides a novel mechanism by which the STN may operationalize its proposed "hold-your-horses" role. The co-occurrence of mPFC-STN theta phase synchronization and STN theta-gamma PAC reflects a neural substrate for fronto-subthalamic communication during conflict processing. More broadly, it may be a general mechanism for neuronal interactions in the cortico-basal ganglia circuits via a combination of long-range, within-frequency phase synchronization and local cross-frequency PAC.

Interhemispheric interactions between the right angular gyrus and the left motor cortex: a transcranial magnetic stimulation study.

The interconnection of the angular gyrus of right posterior parietal cortex (PPC) and the left motor cortex (LM1) is essential for goal-directed hand movements. Previous work with transcranial magnetic stimulation (TMS) showed that right PPC stimulation increases LM1 excitability, but right PPC followed by left PPC-LM1 stimulation (LPPC-LM1) inhibits LM1 corticospinal output compared with LPPC-LM1 alone. It is not clear if right PPC-mediated inhibition of LPPC-LM1 is due to inhibition of left PPC or to combined effects of right and left PPC stimulation on LM1 excitability. We used paired-pulse TMS to study the extent to which combined right and left PPC stimulation, targeting the angular gyri, influences LM1 excitability. We tested 16 healthy subjects in five paired-pulsed TMS experiments using MRI-guided neuronavigation to target the angular gyri within PPC. We tested the effects of different right angular gyrus (RAG) and LM1 stimulation intensities on the influence of RAG on LM1 and on influence of left angular gyrus (LAG) on LM1 (LAG-LM1). We then tested the effects of RAG and LAG stimulation on LM1 short-interval intracortical facilitation (SICF), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). The results revealed that RAG facilitated LM1, inhibited SICF, and inhibited LAG-LM1. Combined RAG-LAG stimulation did not affect SICI but increased LICI. These experiments suggest that RAG-mediated inhibition of LAG-LM1 is related to inhibition of early indirect (I)-wave activity and enhancement of GABAB receptor-mediated inhibition in LM1. The influence of RAG on LM1 likely involves ipsilateral connections from LAG to LM1 and heterotopic connections from RAG to LM1.NEW & NOTEWORTHY Goal-directed hand movements rely on the right and left angular gyri (RAG and LAG) and motor cortex (M1), yet how these brain areas functionally interact is unclear. Here, we show that RAG stimulation facilitated right hand motor output from the left M1 but inhibited indirect (I)-waves in M1. Combined RAG and LAG stimulation increased GABAB, but not GABAA, receptor-mediated inhibition in left M1. These findings highlight unique brain interactions between the RAG and left M1.

A data quality assessment to inform hypertension surveillance using primary care electronic medical record data from Alberta, Canada.

BACKGROUND: Hypertension is a common chronic condition affecting nearly a quarter of Canadians. Hypertension surveillance in Canada typically relies on administrative data and/or national surveys. Routinely-captured data from primary care electronic medical records (EMRs) are a complementary source for chronic disease surveillance, with longitudinal patient-level details such as sociodemographics, blood pressure, weight, prescribed medications, and behavioural risk factors. As EMR data are generated from patient care and administrative tasks, assessing data quality is essential before using for secondary purposes. This study evaluated the quality of primary care EMR data from one province in Canada within the context of hypertension surveillance. METHODS: We conducted a cross-sectional, descriptive study using primary care EMR data collected by two practice-based research networks in Alberta, Canada. There were 48,377 adults identified with hypertension from 53 clinics as of June 2018. Summary statistics were used to examine the quality of data elements considered relevant for hypertension surveillance. RESULTS: Patient year of birth and sex were complete, but other sociodemographic information (ethnicity, occupation, education) was largely incomplete and highly variable. Height, weight, body mass index and blood pressure were complete for most patients (over 90%), but a small proportion of outlying values indicate data inaccuracies were present. Most patients had a relevant laboratory test present (e.g. blood glucose/glycated hemoglobin, lipid profile), though a very small proportion of values were outside a biologically plausible range. Details of prescribed antihypertensive medication, such as start date, strength, dose, frequency, were mostly complete. Nearly 80% of patients had a smoking status recorded, though only 66% had useful information (i.e. categorized as current, past, or never), and less than half had their alcohol use described; information related to amount, frequency or duration was not available. CONCLUSIONS: Blood pressure and prescribed medications in primary care EMR data demonstrated good completeness and plausibility, and contribute valuable information for hypertension epidemiology and surveillance. The use of other clinical, laboratory, and sociodemographic variables should be used carefully due to variable completeness and suspected data errors. Additional strategies to improve these data at the point of entry and after data extraction (e.g. statistical methods) are required.

Deep brain stimulation and recordings: Insights into the contributions of subthalamic nucleus in cognition.

Recent progress in targeted interrogation of basal ganglia structures and networks with deep brain stimulation in humans has provided insights into the complex functions the subthalamic nucleus (STN). Beyond the traditional role of the STN in modulating motor function, recognition of its role in cognition was initially fueled by side effects seen with STN DBS and later revealed with behavioral and electrophysiological studies. Anatomical, clinical, and electrophysiological data converge on the view that the STN is a pivotal node linking cognitive and motor processes. The goal of this review is to synthesize the literature to date that used DBS to examine the contributions of the STN to motor and non-motor cognitive functions and control. Multiple modalities of research have provided us with an enhanced understanding of the STN and reveal that it is critically involved in motor and non-motor inhibition, decision-making, motivation and emotion. Understanding the role of the STN in cognition can enhance the therapeutic efficacy and selectivity not only for existing applications of DBS, but also in the development of therapeutic strategies to stimulate aberrant circuits to treat non-motor symptoms of Parkinson's disease and other disorders.

Bimanual but not unimanual finger movements are triggered by a startling acoustic stimulus: evidence for increased reticulospinal drive for bimanual responses.

The relative contributions of reticulospinal versus corticospinal pathways for movement production are thought to be dependent on the type of response involved. For example, unilateral distal movements involving the hand and finger have been thought to be primarily driven by corticospinal output, whereas bilateral responses are considered to have greater reticulospinal drive. The current study investigated whether a difference in the relative contribution of reticulospinal drive to a bimanual versus unimanual finger movement could be assessed using a StartReact protocol. The StartReact effect refers to the early and involuntary initiation of a prepared movement when a startle reflex is elicited. A decreased response latency on loud stimulus trials where a startle reflex is observed in sternocleidomastoid (SCM+ trials) confirms the StartReact effect, which is attributed to increased reticulospinal drive associated with engagement of the startle reflex circuitry. It was predicted that a StartReact effect would be absent for the predominantly corticospinal-mediated unimanual finger movement but present for the bimanual finger movement due to stronger reticulospinal drive. Results supported both predictions as reaction time was statistically equivalent for SCM+ and SCM- trials during unimanual finger movements but significantly shorter for SCM+ trials during bimanual finger movements. These results were taken as strong and novel evidence for increased reticulospinal output for bimanual finger movements.NEW & NOTEWORTHY The relative contributions of reticulospinal and corticospinal pathways to movement initiation are relatively unknown but appear to depend on the involved musculature. Here, we show that unimanual finger movements, which are predominantly initiated via corticospinal pathways, are not triggered at short latency by a startling acoustic stimulus (SAS), while bimanual finger movements are triggered by the SAS. This distinction is attributed to increased reticulospinal drive for bilateral responses.

Methods to improve the quality of smoking records in a primary care EMR database: exploring multiple imputation and pattern-matching algorithms.

BACKGROUND: Primary care electronic medical record (EMR) data are emerging as a useful source for secondary uses, such as disease surveillance, health outcomes research, and practice improvement. These data capture clinical details about patients' health status, as well as behavioural risk factors, such as smoking. While the importance of documenting smoking status in a healthcare setting is recognized, the quality of smoking data captured in EMRs is variable. This study was designed to test methods aimed at improving the quality of patient smoking information in a primary care EMR database. METHODS: EMR data from community primary care settings extracted by two regional practice-based research networks in Alberta, Canada were used. Patients with at least one encounter in the previous 2 years (2016-2018) and having hypertension according to a validated definition were included (n = 48,377). Multiple imputation was tested under two different assumptions for missing data (smoking status is missing at random and missing not-at-random). A third method tested a novel pattern matching algorithm developed to augment smoking information in the primary care EMR database. External validity was examined by comparing the proportions of smoking categories generated in each method with a general population survey. RESULTS: Among those with hypertension, 40.8% (n = 19,743) had either no smoking information recorded or it was not interpretable and considered missing. Those with missing smoking data differed statistically by demographics, clinical features, and type of EMR system used in the clinic. Both multiple imputation methods produced fully complete smoking status information, with the proportion of current smokers estimated at 25.3% (data missing at random) and 12.5% (data missing not-at-random). The pattern-matching algorithm classified 18.2% of patients as current smokers, similar to the population-based survey (18.9%), but still resulted in missing smoking information for 23.6% of patients. The algorithm was estimated to be 93.8% accurate overall, but varied by smoking status category. CONCLUSION: Multiple imputation and algorithmic pattern-matching can be used to improve EMR data post-extraction but the recommended method depends on the purpose of secondary use (e.g. practice improvement or epidemiological analyses).

Validation of a case definition for speech and language disorders: In community-dwelling older adults in Alberta.

OBJECTIVE: To validate a case definition for speech and language disorders in community-dwelling older adults and to determine the prevalence of speech and language disorders in a primary care population. DESIGN: This is a combined case definition validation and cross-sectional prevalence study. Chart review was considered the reference standard and was used to estimate prevalence. This study used de-identified electronic medical record data from participating SAPCReN-CPCSSN (Southern Alberta Primary Care Research Network-Canadian Primary Care Sentinel Surveillance Network) primary care clinics. SETTING: Southern Alberta. PARTICIPANTS: Men and women aged 55 years and older who had visited a SAPCReN-CPCSSN physician or nurse practitioner at least once in the 2 years before the beginning of the study. MAIN OUTCOME MEASURES: Validation analysis included estimation of sensitivity, specificity, positive predictive value, and negative predictive value. Prevalence was the other main outcome measure. RESULTS: The prevalence of speech and language disorders within the sample of 1384 patients was 1.2%. The case definition had a favourable specificity (99.9%, 95% CI 99.6% to 100.0%), positive predictive value (75.6%, 95% CI 25.4% to 96.6%), and negative predictive value (99.0%, 95% CI 98.8% to 99.2%). Sensitivity was not sufficient for validity (18.8%, 95% CI 4.05% to 45.6%). CONCLUSION: The case definition did not meet an acceptable standard for validity and thus cannot be used for future epidemiologic research. However, owing to the case definition's high positive predictive value, it might be useful for clinical purposes and for cohort studies. Finally, while the case definition did not prove valid, this study has provided a conservative estimate of prevalence (1.2%) given the case definition's high specificity.

High-intensity transcranial magnetic stimulation reveals differential cortical contributions to prepared responses.

Corticospinal output pathways have typically been considered to be the primary driver for voluntary movements of the hand/forearm; however, more recently, reticulospinal drive has also been implicated in the production of these movements. Although both pathways may play a role, the reticulospinal tract is thought to have stronger connections to flexor muscles than to extensors. Similarly, movements involuntarily triggered via a startling acoustic stimulus (SAS) are believed to receive greater reticular input than voluntary movements. To investigate a differential role of reticulospinal drive depending on movement type or acoustic stimulus, corticospinal drive was transiently interrupted using high-intensity transcranial magnetic stimulation (TMS) applied during the reaction time (RT) interval. This TMS-induced suppression of cortical drive leads to RT delays that can be used to assess cortical contributions to movement. Participants completed targeted flexion and extension movements of the wrist in a simple RT paradigm in response to a control auditory go signal or SAS. Occasionally, suprathreshold TMS was applied over the motor cortical representation for the prime mover. Results revealed that TMS significantly increased RT in all conditions. There was a significantly longer TMS-induced RT delay seen in extension movements than in flexion movements and a greater RT delay in movements initiated in response to control stimuli compared with SAS. These results suggest that the contribution of reticulospinal drive is larger for wrist flexion than for extension. Similarly, movements triggered involuntarily by an SAS appear to involve greater reticulospinal drive, and relatively less corticospinal drive, than those that are voluntarily initiated. NEW & NOTEWORTHY Through the use of the transcranial magnetic stimulation-induced silent period, we provide novel evidence for a greater contribution of reticulospinal drive, and a relative decrease in corticospinal drive, to movements involuntarily triggered by a startle compared with voluntary movements. These results also provide support for the notion that both cortical and reticular structures are involved in the neural pathway underlying startle-triggered movements. Furthermore, our results indicate greater reticulospinal contribution to wrist flexion than extension movements.

Quality of warfarin management in primary care: Determining the stability of international normalized ratios using a nationally representative prospective cohort.

OBJECTIVE: To determine the stability of warfarin anticoagulation using a nationally representative sample of Canadian primary care patients and providers. DESIGN: Prospective cohort study. SETTING: Primary care practices associated with the Canadian Primary Care Sentinel Surveillance Network. PARTICIPANTS: Adult warfarin users with 7 or more evaluable international normalized ratio (INR) readings. MAIN OUTCOMES MEASURES: International normalized ratio time in therapeutic range (TTR) determined using the Rosendaal method; TTR above 75% was considered good INR control and TTR below 60% was considered poor INR control. The primary outcome was the proportion of all warfarin users (using an INR target range of 2.0 to 3.5) with good INR control during their first year taking warfarin who have poor INR control the following year. Secondary outcomes included the TTR using an INR target of 2.0 to 3.0 when restricted to patients with known atrial fibrillation (AF) or venous thromboembolism (VTE); and the proportion of INR values below the target of 2.0 and above the targets of 3.0 and 3.5 in the year before the availability of other oral anticoagulants. RESULTS: Among 18 303 adult warfarin users (mean age of 71.0 years, 46.6% female), the median TTR (INR target range of 2.0 to 3.5) was 77.4% (interquartile range of 64.6% to 86.4%). The TTR was above 75% in 56.0% of patients and below 60% in 19.3% of patients. Of those exhibiting good INR control in year 1 of anticoagulation therapy, only 10.2% had poor control the following year. When restricted to patients with known AF or VTE (89.7% with AF and 13.5% with VTE), and assuming an INR target range of 2.0 to 3.0, the TTR was 67.8% (interquartile range of 54.8% to 77.9%). Of these patients, 27.9% had INR values below 2.0, and 19.4% and 8.6% had values above 3.0 and 3.5, respectively. CONCLUSION: Primary care warfarin management produces a TTR comparable to that in randomized trials, with out-of-range INR values 3 times more likely to predispose to thrombosis (INR of < 2.0) than to hemorrhage (INR of > 3.5). A history of good INR control does predict future INR stability and meaningfully informs decisions to switch established warfarin users onto newer agents.

Structure and Metallicity of Phase V of Hydrogen.

A new phase V of hydrogen was recently claimed in experiments above 325 GPa and 300 K. Because of the extremely small sample size at such record pressures the measurements were limited to Raman spectroscopy. The experimental data on increase of pressure show decreasing Raman activity and darkening of the sample, which suggests band gap closure and impending molecular dissociation, but no definite conclusions could be reached. Furthermore, the available data are insufficient to determine the structure of phase V, which remains unknown. Introducing saddle-point ab initio random structure searching, we find several new structural candidates of hydrogen which could describe the observed properties of phase V. We investigate hydrogen metallization in the proposed candidate structures, and demonstrate that smaller band gaps are associated with longer bond lengths. We conclude that phase V is a stepping stone towards metallization.

Antidepressant and antipsychotic prescribing in primary care for people with dementia.

OBJECTIVE: To use data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) to evaluate the prevalence of antidepressant and antipsychotic prescriptions among patients with no previous depression or psychosis diagnoses, and to identify the factors associated with the use of these drugs in this population. DESIGN: Retrospective cohort study using data derived from CPCSSN. SETTING: Primary care practices associated with CPCSSN. PARTICIPANTS: Patients who were born before 1949; who were associated with a CPCSSN primary care practitioner between October 1, 2007, and September 30, 2013; and whose electronic medical records contained data from at least 6 months before and 12 months after the date of dementia diagnosis. MAIN OUTCOME MEASURES: Prescription for an antidepressant or antipsychotic medication in the absence of a depression or psychosis diagnosis. Multivariable models were fitted to determine estimated odds ratios (ORs) and were adjusted for age and sex. RESULTS: Of the 3252 patients without a depression diagnosis, 8.5% received a new prescription for an antidepressant in the 12 months following their diagnosis of dementia. Prescribing was reduced in association with older age (OR of 0.86 per 5-year age increase, P=.001) and male sex (OR=0.77, P=.056), and prescribing increased in association with prescription of cholinesterase inhibitor medications (OR=1.57, P=.003). Of the 4262 patients without a diagnosis of psychosis, 6.1% received a new prescription for an antipsychotic in the 12 months following their diagnosis of dementia. Higher rates of antipsychotic prescriptions were reported in men (OR=1.31, P=.046), those receiving a prescription for steroids (OR=1.90, P=.037), and those diagnosed with Parkinson disease (OR 1.58, P=.051). CONCLUSION: A substantial number of patients with dementia are being prescribed antidepressant or antipsychotic medications by their primary care practitioners without evidence of depression or psychosis in their electronic medical records.

Team-based comanagement of diabetes in rural primary care.

OBJECTIVE: To explore clinical indicators among patients with diabetes in southern Alberta and assess changes over time, and to compare patients with diabetes attending a reference clinic (RC), which had adapted its service model to address the specific needs of the patient population, with patients with diabetes attending comparison clinics (CCs) in the same region. DESIGN: Analysis of longitudinal data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). SETTING: Rural southern Alberta. PARTICIPANTS: A community-based family medicine clinic and the 6 other CPCSSN clinics in the same region at the time of the study. MAIN OUTCOME MEASURES: A range of data elements from patients with diabetes within the RC, as well as from patients with diabetes from the CCs, were analyzed by CPCSSN to compare rates of comorbidity and mean body mass index, hemoglobin A1c levels, and blood pressure, as well as service use and measurement frequency. Rate of change per year was modeled longitudinally for each of the outcomes. RESULTS: The RC had higher proportions of patients with comorbid conditions and a consistently higher mean body mass index. Mean HbA1c levels varied minimally between the RC and CCs, with both sets worsening slightly. However, the rate of worsening among patients with diabetes in the RC was found to be significantly greater (P < .05) than for those in the CCs. Blood pressure also varied minimally between the RC and the CCs, with both sets improving; however, the RC had a significantly greater (P < .001) rate of improvement than the CCs did. Finally, a greater proportion of patients in the RC had complete data for these 3 outcome measures, and RC patients made a greater number of clinic visits compared with the CC patients (P < .001). CONCLUSION: This study describes a team-based comanagement organizational model and might provide useful commentary about organizational effectiveness in primary care. Although improvement in health outcomes cannot be directly attributed to any specific change in clinic organization, some statistically and likely clinically significant benefit was found associated with the service model of the RC in a relatively medically and socially challenged patient population and in a conservative evaluative design.

Go-activation endures following the presentation of a stop-signal: evidence from startle.

It has been proposed that, in a stop-signal task (SST), independent go- and stop-processes "race" to control behavior. If the go-process wins, an overt response is produced, whereas, if the stop-process wins, the response is withheld. One prediction that follows from this proposal is that, if the activation associated with one process is enhanced, it is more likely to win the race. We looked to determine whether these initiation and inhibition processes (and thus response outcomes) could be manipulated by using a startling acoustic stimulus (SAS), which has been shown to provide additional response activation. In the present study, participants were to respond to a visual go-stimulus; however, if a subsequent stop-signal appeared, they were to inhibit the response. The stop-signal was presented at a delay corresponding to a probability of responding of 0.4 (determined from a baseline block of trials). On stop-trials, a SAS was presented either simultaneously with the go-signal or stop-signal or 100, 150, or 200 ms following the stop-signal. Results showed that presenting a SAS during stop-trials led to an increase in probability of responding when presented with or following the stop-signal. The latency of SAS responses at the stop-signal + 150 ms and stop-signal + 200 ms probe times suggests that they would have been voluntarily inhibited but instead were involuntarily initiated by the SAS. Thus results demonstrate that go-activation endures even 200 ms following a stop-signal and remains accessible well after the response has been inhibited, providing evidence against a winner-take-all race between independent go- and stop-processes. NEW & NOTEWORTHY: In this study, a startling acoustic stimulus (SAS) was used to determine whether response outcome could be manipulated in a stop-signal task. Results revealed that presenting a SAS during stop-signal trials led to an increase in probability of responding even when presented 200 ms following the stop-signal. The latency of SAS responses indicates that go-activation remains accessible and modifiable well after the response is voluntarily inhibited, providing evidence against an irrevocable commitment to inhibition.