Model For Repeated Measures Research Articles

Utility of a controlled amphetamine withdrawal paradigm among adults who use methamphetamine: A pilot clinical trial.

The continued increase in prevalence of methamphetamine use in the United States has resulted in a significant increase in the number of patients entering treatment for methamphetamine use. However, no robustly efficacious pharmacologic treatment for methamphetamine use or withdrawal has been identified to date after stopping methamphetamine use. Given the association between methamphetamine withdrawal and relapse during early treatment, this study tested a controlled d-amphetamine withdrawal paradigm among methamphetamine-using individuals. Treatment-seeking adults who used methamphetamine (N = 34; 47% female; 100% white) were enrolled in a 4-week, randomized, double-blind, placebo-controlled trial in a residential setting, in which all participants were maintained on d-amphetamine (30 mg BID) during week 1, then half were switched to placebo during weeks 2-3. All participants received placebo during week 4. Outcomes included vital signs, withdrawal, cravings for methamphetamine, mood, and cognition. Bivariate analyses tested treatment group differences on baseline demographic and outcome variables. Repeated measures models examined main and interaction effects of treatment over time. Participants were successfully randomized and safely stabilized on d-amphetamine. Craving for methamphetamine increased during weeks 2-3 in the placebo group relative to those on d-amphetamine. Interactions with age and heart rate were noted. To our knowledge, this is the first double-blind, placebo-controlled trial measuring pharmacologic effects of abruptly stopping controlled d-amphetamine administration in adults who use methamphetamine. Results support the potential of this withdrawal paradigm to further examine the efficacy of pharmacologic agents in ameliorating methamphetamine withdrawal symptoms.

What happens to diet quality in people newly diagnosed with type 2 diabetes? The 3D case-series study.

Diet quality plays an important role in the prevention of diabetes-related complications in people with type 2 diabetes mellitus (T2DM). However, evidence is scarce on how diet quality typically changes over time after diagnosis. The present study aimed to describe how the diet quality of individuals newly diagnosed with T2DM changes over a 12-month period and to identify factors associated with diet quality changes. A 12-month prospective, observational case-series study was undertaken. Two-hundred and twenty-five Australian adults (56% men) newly diagnosed with T2DM were recruited from the Diabetes Australia national database. Participants completed five interviewer-administered surveys over 12months: baseline, 3, 6, 9 and 12months. Demographic, physical and health characteristics, and dietary intake data were collected at each timepoint. Diet quality was assessed using the Dietary Approaches to Stop Hypertension (DASH) scoring tool. To assess changes in DASH, energy, fruit and vegetable intake over time, repeated measure analyses of variance were used. Multivariate repeated measures models investigated characteristics associated with these dietary changes. The mean DASH score of the sample remained stable at 24.0 across the 12months. Very few participants (6.8%) improved diet quality consistently across the study period. No associations between DASH, energy, fruit or vegetable intake over time and characteristics were observed. This observational study suggests that without dedicated interventions (the natural course), most people newly diagnosed with T2DM will not achieve meaningful diet quality change. The development of cost-effective interventions to achieve sustained diet quality change early after diagnosis are warranted.

Associations of Body Mass Index-Metabolic Phenotypes with Cognitive Decline in Parkinson’s Disease

Background: Growing evidence suggests important effects of body mass index (BMI) and metabolic status on neurodegenerative diseases. However, the roles of BMI and metabolic status on cognitive outcomes in Parkinson’s disease (PD) may vary and are yet to be determined. Methods: In total, 139 PD patients from the whole PD cohort in Parkinson’s Progression Markers Initiative database underwent complete laboratory measurements, demographic and anthropometric parameters at baseline, and were enrolled in this study. Further, they were categorized into 4 different BMI-metabolic status phenotypes using Adult Treatment Panel-III criteria. Motor and cognition scales at baseline and longitudinal changes after a 48-month follow-up were compared among the 4 groups. Repeated-measure linear mixed models were performed to compare PD-related biomarkers among BMI-metabolic status phenotypes across time. Results: We found that PD patients in the metabolically unhealthy normal weight group showed more cognitive decline in global cognition and visuospatial perception after a 48-month follow-up than those in the other 3 groups (p < 0.05). No difference was found in motor scales among different BMI-metabolic status phenotypes. Finally, compared to the metabolically healthy normal weight group, the metabolically healthy obesity group had lower CSF Aβ42 and serum neurofilament levels in repeated-measure linear mixed models adjusting for age, gender, APOE e4 carrier status, and years of education (p = 0.031 and 0.046, respectively). Conclusion: The MUNW phenotype was associated with a rapid cognitive decline in PD.

Long-term predictors of severe exacerbations and mortality in a cohort of well-characterised adults with asthma

BackgroundWe aimed to explore long-term predictors of severe exacerbations and mortality in adults with well-characterised asthma.Study design and methodsAdults (aged ≥ 15) with an objectively verified diagnosis of asthma were recruited from a Danish respiratory outpatient clinic between 1974 and 1990. All individuals were followed in Danish registries for vital status, hospital admissions for asthma and cause of death until end of 2017. Predictors of exacerbations were obtained from a repeated measures model. Standardised mortality rates (SMR) for all-causes were compared with the Danish background population. Hazard ratios for mortality were obtained from a cox proportional hazards model in a two-step process.ResultsAt baseline, the cohort comprised 1071 patients (mean age 38, SD 16, 61% women), of whom 357 (33%) died during follow-up, with 93 (26%) dying from asthma (primary diagnosis). We found an SMR of 1.24 (95% CI 1.11–1.37, p < 0.001) for all-cause mortality. Baseline predictors for asthma-related death and repeated severe exacerbations were increasing age, ever smoker, FEV1 < 80% pred., high blood eosinophils, longer duration of symptoms and use of SABA > twice daily. Being non-atopic, having a positive histamine challenge test and symptoms more than twice a week were also predictors of repeated exacerbations.ConclusionsMarkers of poor asthma control, including high use of SABA, are predictors of long-term exacerbation rate and mortality over 30 years in patients with well-characterised asthma. Improving asthma control, including lung function and reducing use of reliever medication, is vital for improving the long-term outcome of asthma.

Comparison of different symmetry indices for the quantification of dynamic joint angles

BackgroundSymmetry is a sign of physiological and healthy movements, as pathologies are often described by increased asymmetries. Nevertheless, based on precisely measured data, even healthy individuals will show small asymmetries in their movements. However, so far there do not exist commonly accepted methods and reference values for gait symmetry in a healthy collective. Therefore, a comparison and presentation of reference values calculated by 3 different methods of symmetry indices for lower limb joint angles during walking, ascending, and descending stairs were shown.MethodsThirty-five healthy participants were analyzed during walking, ascending, and descending stairs with the help of the inertial measurement system MyoMotion. Using the normalized symmetry index (SInorm), the symmetry index (SI) as the integral of the symmetry function, and another normalized symmetry index (NSI), the symmetry of joint angles was evaluated. For statistical evaluation of differences, repeated measurement models and Bland–Altman-Plots were used.ResultsApart from a bias between the symmetry indices, they were comparable in the predefined limits of 5%. For all parameters, significantly higher asymmetry was found for ankle dorsi/-plantarflexion, compared with the hip and knee flexion. Moreover, the interaction effect of the joint and movement factors was significant, with an increased asymmetry of the hip and knee during descending stairs greater than while ascending stairs or walking, but a reduced symmetry of the ankle during walking when compared to descending. The movement only showed significant effects when analyzing the SInorm.ConclusionEven for healthy individuals, small asymmetries of movements were found and presented as reference values using 3 different symmetry indices for dynamic lower limb joint angles during 3 different movements. For the quantification of symmetrical movements differences between the joints, movements, and especially their interaction, are necessary to be taken into account. Moreover, a bias between the methods should be noted. The potential for each presented symmetry index to identify pathological movements or track a rehabilitation process was shown but has to be proven in further research.Trial registration: DRKS00025878.

Quantifying the relationship between disability progression and quality of life in patients treated for NMOSD: Insights from the SAkura studies

BackgroundTo date, no specific scales have been developed to explore the impact of neuromyelitis optica spectrum disorder (NMOSD)-related disability on quality of life (QoL). The Expanded Disability Status Scale (EDSS) and the EuroQol 5-dimensions (EQ-5D) have been used to assess disability and QoL, respectively, in patients with NMOSD. However, there is limited evidence surrounding their use in this condition. We compared EDSS and EQ-5D data across two clinical trials to quantify the relationship between disability and QoL in patients with NMOSD. MethodsSAkuraSky (NCT02028884) and SAkuraStar (NCT02073279) were Phase 3, multicenter, randomized, international, double-blind, placebo-controlled, parallel-assignment studies of satralizumab, administered in combination with baseline immunosuppressants (SAkuraSky) or as monotherapy (SAkuraStar). EDSS and EQ-5D were assessed at baseline and at 24-week intervals thereafter. The relationship between disability and QoL was assessed by estimating EQ-5D utilities (UK tariff) for each incremental EDSS category. A repeated-measures linear model was used to regress health utilities on EDSS score-derived health states. ResultsOverall, 176 patients underwent at least one EDSS assessment and completed an EQ-5D survey and were included in this analysis. There was a clear association between mean EQ-5D score and EDSS score, with decreases in QoL being observed at each incremental increase in disability. The relationship between EDSS and EQ-5D score remained consistent across the different treatment groups. ConclusionsThese results, generated from high-quality clinical trial data, demonstrated a strong and consistent relationship between disability and QoL in patients with NMOSD.

Sequential Cerebrospinal Fluid Sampling in Horses: Comparison of Sampling Times and Two Different Collection Sites

Analysis of the cerebrospinal fluid (CSF) is important as a complementary test in horses with neurologic diseases, and sequential analysis may provide information about the treatment response or evolution and quantitative measures of the CSF drug concentration during treatment. The aim of this study was to compare erythrocyte and nucleated cell counts and protein concentration in multiple CSF samples obtained sequentially from two different puncture sites in clinically healthy horses. Eight and 12 horses, with no evidence of neurologic disease, were subjected to CSF collection from the atlanto-occipital (AO) and C1–C2 spaces, respectively. Cytologic and chemical analyses were performed on the CSF obtained at five sampling times (T1, T2, T3, T4, and T5). Repeated measures models were used to compare the mean erythrocyte count, nucleated cell count, and total protein concentration between the AO and C1–C2 groups at each sampling time. C1–C2 CSF had a significantly higher total protein concentration at T1 and T4 than that of AO CSF. All total protein concentration values remained within the reference interval (<90 mg/dL) for all sampling times and groups. No statistical difference was present between results at T2, T3, T4, and T5 and at T1 in both groups for all analyses. In conclusion, five consecutive AO or C1–C2 CSF collections with at least a 7-d interval did not result in alterations in the CSF erythrocyte and nucleated cell counts and total protein concentrations and did not interfere with the CSF analysis results.

Baseline characteristics and effects of fingolimod on cognitive performance in patients with relapsing-remitting multiple sclerosis.

Background and purposeStudies reporting the baseline determinants of cognitive performance and treatment effect on cognition in patients with multiple sclerosis (MS) are limited. We investigated the baseline correlates of cognition and the long‐term treatment effects of fingolimod 0.5 mg once daily on cognitive processing speed and attention in patients with relapsing‐remitting MS.MethodsThis post hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N = 1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline 3‐second Paced Auditory Serial Addition Test (PASAT‐3) scores (Spearman's rank test) and the changes from baseline in PASAT‐3 (mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo‐fingolimod switched (from Month 24 up to 120 months) groups. Additionally, the predictive value of PASAT‐3 score for future disease outcomes was assessed (Cox or logistic regression models).ResultsAmong the variables assessed, lower PASAT‐3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p < 0.0001 for all). Fingolimod significantly improved PASAT‐3 scores from baseline versus placebo at 6 (1.3; p = 0.0007), 12 (1.1; p = 0.0044) and 24 months (1.1; p = 0.0028), with a sustained effect (overall treatment effect p = 0.0012) up to 120 months. Improvements were seen regardless of baseline cognitive status (PASAT quartile). Baseline PASAT‐3 score was predictive of both clinical and magnetic resonance imaging measures of disease activity at Month 24 (p < 0.001 for all).ConclusionEarly fingolimod treatment may offer long‐term cognitive benefit in patients with relapsing‐remitting MS.

Trajectories of high-sensitivity cardiac troponin I in the two decades before cardiovascular death in Whitehall II

Abstract Background High-sensitivity cardiac troponin may be a promising biomarker that could be used for personalised cardiovascular risk prediction and monitoring in the general population. Temporal changes in high-sensitivity cardiac troponin before cardiovascular death are largely unexplored. Purpose Using the longitudinal Whitehall II cohort, we evaluated whether three serial high-sensitivity cardiac troponin I measurements over 15 years improved prediction of cardiovascular death when compared to a single time point at baseline. Methods Whitehall II is an ongoing longitudinal observation cohort study of 10,308 civil servants, and we included participants who had at least one cardiac troponin measurement and outcome data available. We constructed time trajectories to evaluate the temporal pattern of cardiac troponin I in those who died from cardiovascular disease as compared to those who did not. Cox regression and joint models were used to investigate the association of cardiac troponin I in relation to cardiovascular death using single time point (at baseline) and repeated measurements (at baseline, 10 and 15 years), respectively. The discriminative ability was assessed by the concordance index. Results In total, we included 7,293 individuals (mean age of 58 years [SD 7] at baseline, 29.4% women). Of these, 5,818 (79.8%) and 4,045 (55.5%) individuals had a second and third cardiac troponin I concentration measured, respectively. Cardiovascular death occurred in 281 (3.9%) individuals during a median follow-up of 21.4 [IQR, 15.8 to 21.8] years. In the 21-year trajectories of cardiac troponin I, we observed higher baseline concentrations in those who died due to cardiovascular disease as compared to those who did not (median 5 [IQR, 2 to 9] ng/L versus 3 [IQR, 2 to 5] ng/L respectively, Figure). Cardiac troponin I was an independent predictor of cardiovascular death, and the hazard ratio (HR) derived from the joint model that included serial cardiac troponin measurements was higher than the HR derived from the single time point model (single time point model: adjusted HR 1.53, 95% Confidence Interval [CI] 1.37 to 1.70 per naturally log transformed unit of cardiac troponin I, versus repeated measurements model: adjusted HR 1.79, 95% CI 1.58 to 2.02). The discriminative ability of the cardiac troponin model improved when using repeated measurements (concordance index of unadjusted cardiac troponin models, single time point: 0.668 versus repeated measurements: 0.724). Conclusions Our study shows that cardiac troponin I trajectories were persistently higher among individuals who died from cardiovascular disease. Cardiac troponin I is a strong independent predictor of cardiovascular death, and incorporating repeated measurements of cardiac troponin improves cardiovascular risk prediction in the general population. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Cardiac troponin I measurements and analysis were supported by were supported by Siemens Healthineers. The study was supported by Health Data Research UK which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust. NLM is supported by the British Heart Foundation through a Senior Clinical Research Fellowship (FS/16/14/32023), Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216). The funders had no role in the study and the decision to submit this work to be considered for publication.

PSX-B-19 Behaviour of cows while being tested for methane emissions using the greenfeed system

Abstract Increased focus on sustainability is driving a need for environmental efficiency traits in dairy cattle breeding. Breeding for reduced emission of methane, an inevitable product of fermentation in ruminants, is increasingly being explored. Methods to measure methane emissions vary but can be impacted by cow behaviour. As part of an on-going project to develop genomic tools for breeding resilient dairy cows, we explored changes in cow behaviour over time during methane emission measurements. First lactation heifers (n = 49) were tested in tie-stall housing at a research herd in Ontario, Canada. Animals were tested over 5 consecutive days at 08:00h, 12:00h, and 16:00h each day for a 10-min period using the GreenFeed system (C-Lock Inc., Rapid City, SD, USA). The frequency of movement (body shifts and leg lifts) and the number of seconds the cow removed her head from the machine were recorded. The effect of day on the average frequency of movements or time the cow’s head was outside of the machine was assessed using a repeated measures model. In general, cows moved their legs the most on day 1 of testing (76 ± 5.0 movements per 10 min), after which it numerically decreased (e.g., day 5: 68 ± 5.0 movements per 10 min, P = 0.1110). A similar effect was observed for seconds the cow had her head out of the machine (P = 0.0650). Cows spent an average of 39 ± 5.7 sec with their head outside of the machine on day 1 versus 25 ± 3.6 sec on day 5 (P = 0.0499). These preliminary results suggest that cows adapt to the testing conditions; however, changes in their behaviour were minor and do not intervene with recording of methane emissions using the GreenFeed system.

Do Walking Distance and Time Away from the Paddock Influence Daily Behaviour Patterns and Milk Yield of Grazing Dairy Cows?

Simple SummaryDairy cows managed on pasture may need to walk several kilometres to reach the milking parlour to be milked and, thus, may spend an extended time away from the paddock without access to pasture. While cows have a diverse behavioural repertoire, at a minimum they must graze, ruminate and lie down; therefore, time spent away from the paddock will affect how these behavioural needs are met. We investigated how walking distance to the milking parlour and total time spent away from the paddock affected daily grazing, ruminating and lying behaviours of dairy cattle managed in three groups. The devices automatically monitored cow behaviour and the time spent walking and waiting outside the paddock. We showed that cows spent more time grazing and less time ruminating on days with longer walking distances, which may, in part, be due to greater energy expenditure resultant of walking. When cows spent more time away from the paddock, they had a reduced lying time, and the cows in one of the groups produced less milk. Thus, limiting the walking distance and time spent away from the paddock are two factors that could provide greater opportunities for cows to engage in daily behavioural patterns that meet individual needs. In pasture-based systems, cows may spend several hours away from the paddock and may also walk several kilometres to meet daily milking requirements; this could lead cows to experience time constraints for grazing, ruminating and lying time in the paddock. This study investigated how walking distance and time spent away from the paddock affected daily behavioural patterns (i.e., grazing, ruminating and lying time) and milk yield. Dairy cows were managed in three rotationally grazed groups (n = 29 cows each) on the same farm and milked twice daily. A triaxial ear tag accelerometer on each cow recorded daily duration of grazing and ruminating, and a leg-based accelerometer recorded the daily lying time, for 13 days. GPS collars on four cows per group recorded the daily walking distance and total time away from the paddock for the group. A mixed repeated measures model tested how time off-paddock and walking distance affected the daily behavioural patterns; age, breed, milk yield and maximum ambient temperature were used as covariates with group as the observational unit. A second similar model tested how these factors affected milk yield. Walking distance and time spent away from the paddock were not correlated. When daily walking distance increased (to a maximum of 4 km/d), cows spent more time grazing and less time ruminating, but lying time was not affected. This result may, in part, be related to the greater energy expenditure demands for walking longer distances and milk production. When time away from the paddock increased (to a maximum of 4 h/d), cows spent less time lying, but grazing and ruminating times were not affected. Milk yield was not affected by walking distance, but one of the groups experienced a lower milk yield when time away from the paddock was increased. This result suggests that, for some cows, lying times may be shorter when experiencing a longer time away from the paddock, which may also affect milk yield. Overall, this study indicates that paddock behaviours are associated with walking distance to the milking parlour and time spent away from the paddock. Efforts to reduce walking distance and time spent away from the paddock are likely to provide cows with greater opportunity to engage in daily behaviours in the paddock that meet their needs and maintain their milk yield.

EFFECT OF TEZEPELUMAB ON LUNG FUNCTION IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA IN THE PHASE 3 NAVIGATOR STUDY

EFFECT OF TEZEPELUMAB ON LUNG FUNCTION IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA IN THE PHASE 3 NAVIGATOR STUDY

Comparison of Healthcare Resource Utilization Between Patients Who Engaged or Did Not Engage With a Prescription Digital Therapeutic for Opioid Use Disorder.

BackgroundA prescription digital therapeutic (PDT) (reSET-O®) may expand access to behavioral treatment for patients with opioid use disorder (OUD) treated with buprenorphine, but long-term data on effectiveness are lacking.ObjectiveTo compare real-world healthcare resource utilization (HCRU) among patients who engaged with reSET-O and buprenorphine compared to similar patients in recovery treated with buprenorphine who did not fill their reSET-O script or engage with the PDT beyond week one.MethodsA retrospective analysis of facility and clinical service claims data was conducted in adults with PDT initiation and between 12 weeks and 9 months of continuous enrollment in a health plan after initiation. Patients who filled their prescription and engaged with the therapeutic were compared to patients who filled the prescription but did not engage beyond week one (NE), and patients who did not fill the prescription (NR) (the latter two groups combined into one group hereafter referred to as “non-engagers”). Comparisons were analyzed using a repeated-measures negative binomial model of encounters/procedures, adjusted for number of days in each period. Associated cost trends assessed using current Medicare reimbursement rates.ResultsA total of 444 patients redeemed a prescription and engaged with the PDT (mean age 37.5 years, 63.1% female, 84% Medicaid), and 64 patients did not engage with the PDT (mean age 39.5 years, 32.8% female, 73.4% Medicaid). Total cost of hospital facility encounters was $2693 for engaged patients vs $6130 for non-engaged patients. Engaged patients had somewhat higher rates of certain clinician services. Total facility and clinician services costs for engaged vs non-engaged patients were $8733 vs $11,441, for a net cost savings over 9 months of $2708 per patient who engaged with reSET-O.ConclusionPatients who engaged with an OUD-specific PDT had a net cost reduction for inpatient and outpatient services of $2708 per patient over 9 months compared to patients who did not engage with the PDT, despite similar levels of buprenorphine adherence.

Association of Lifetime Traumatic Brain Injury and Military Employment with Late-Life ADL Functioning: A Population-Based Prospective Cohort Study

<h3>Research Objectives</h3> To determine associations of lifetime history of traumatic brain injury (TBI) with loss of consciousness (LOC) and military employment with activities of daily living (ADL) in late life. <h3>Design</h3> A population-based prospective cohort study of older adults with a baseline visit and up to 10-years of biennial follow-up visits. <h3>Setting</h3> Seattle-area integrated healthcare delivery system. <h3>Participants</h3> Male (n=2066) and female (n=2887) participants of the Adult Changes in Thought (ACT) study, aged 65+ and dementia-free. <h3>Interventions</h3> We fitted repeated-measures Poisson mixed effects regression models. Military employment and TBI with LOC variables were included as main effects. We included interaction terms with time to allow for different longitudinal trends in ADL difficulties within each exposure group of interest. <h3>Main Outcome Measures</h3> History of TBI with LOC was based on participant self-report during the baseline visit. History of military employment was ascertained based on items addressing the longest and second longest occupations for each participant. ADL functioning was assessed at baseline and biennial follow-up via participant self-reported function on the 6-item Katz ADL index. For analyses, we summed the number of ADLs with which a person reported at least some difficulty (range 0-6). <h3>Results</h3> TBI with LOC before age 40 was associated with greater ADL difficulty at baseline for females (RR=1.44, 95% CI: 1.08-1.93, p=0.01). For males, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age < 40: RR=1.58, 95% CI: 1.20 - 2.08, p = 0.001; age 40+: RR=2.14, 95% CI: 1.24 - 3.68, p = 0.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in males or females. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses. <h3>Conclusions</h3> Future study of the implications of TBI and military employment on late-life physical functioning as measured by performance-based tools in more diverse cohorts is warranted. <h3>Author(s) Disclosures</h3> No conflicts of interest reported.

Evaluation of a medication optimization intervention and predictors of medication adherence, patient satisfaction and medication adverse events in patients with rheumatoid arthritis.

Because effective treatment for rheumatoid arthritis (RA) is dependent on medication use, medication optimization is critically important. Medication adherence, patient satisfaction with care and medication adverse events are core concepts of medication optimization that are either a significant problem and/or understudied in patients with RA. To (1) evaluate treatment effects from a medication optimization intervention; (2) assess treatment differences and changes over time in medication adherence, patient satisfaction, and medication adverse events; and (3) to determine whether age, gender, provider trust, and disease activity affect these outcomes. We conducted a prospective, longitudinal intervention study (N=143 RA patients) using repeated measures models. We did not identify significant intervention effects. For both the medication adherence and patient satisfaction models, the significant predictors in the model included age, gender and trust in provider. Older age, female gender (relative to male), and greater trust in the provider were associated with increased medication adherence scores and patient satisfaction. For the adverse events model, the only significant predictor in the model was gender. Compared with males, females were more likely to report experiencing adverse events. Time was significantly associated with decreased experiences of adverse events. This study has identified important predictors of medication adherence, patient satisfaction and medication adverse events in a sample of patients with RA which can facilitate targeted approaches to improve adherence in those high-risk groups.

Serial DaT-SPECT imaging in asymptomatic carriers of LRRK2 G2019S mutation: 8 years' follow-up.

Carriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of Parkinson's disease (PD). We have studied by serial clinical and dopamine transporter single photon emission computed tomography (DaT-SPECT) evaluations a cohort of asymptomatic carriers of the LRRK2-G2019S mutation in order to evaluate the usefulness of these tools as biomarkers. Here we report the results of the extended follow-up of this cohort at 8years. Seventeen participants, of the 25 available from the 4-year evaluation, completed the 8-year assessment. UPDRS-III, UPSIT test and DaT-SPECT imaging (123 I-ioflupane) were performed. We used repeated-measures linear mixed effects models to examine the changes in DaT binding over time. Three carriers had converted to PD at 4 years. One additional carrier converted at 8 years. PD-converters had lower striatal DaT binding at baseline than non-converters. There was a significant decline of DaT binding over time, with a mean annual rate of 3.5%, with somewhat inter-individual and intra-individual variability and comparable between PD-converters and non-converters. No carrier with DAT binding ratio above an undefined threshold between 0.5 and 0.8 developed PD symptoms. The age-adjusted UPSIT score did not change significantly over time. The rate of conversion to PD at 8years in this cohort aged ~58years at baseline was 16%. The observed decline of DaT binding over time and its association with the phenotype render DaT-SPECT a potentially useful tool for monitoring the premotor stage of the disease, although at the individual level its ability to predict phenoconversion is limited.

Improved body image after uterovaginal prolapse surgery with or without hysterectomy.

The objective was to compare body image and sexual activity and function changes up to 3years after sacrospinous ligament fixation with graft hysteropexy or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy). This was a planned secondary analysis of a multi-center randomized trial of women undergoing prolapse repair with mesh hysteropexy versus hysterectomy. Women were masked to intervention. The modified Body Image Scale (BIS), sexual activity status, and Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) scores were reported at baseline and 1.5, 6, 12, 18, 24, and 36months after surgery. We compared mean BIS and PISQ-IR scores, the proportion of women whose BIS scores met a distribution-based estimate of the minimally important difference (MID), and sexual activity status. Comparisons were analyzed with linear and logistic repeated measures models adjusted for site, intervention, visit, and intervention by visit interaction. Eighty-eight women underwent mesh hysteropexy; 87 underwent hysterectomy. Women were similar with regard to baseline characteristics, mean age 65.9 ± 7.3years, and most had stage III or IV prolapse (81%). Baseline mean BIS scores were not significantly different, improved in both groups by 1.5months, and were sustained through 36months with no differences between groups (all p > 0.05). The estimated BIS MID was 3; and by 36months, more women in the mesh hysteropexy group achieved the MID than in the hysterectomy group (62% vs 44%, p = 0.04). The makeup of the sexually active cohort changed throughout the study, making function comparisons difficult. Body image improves following prolapse surgery whether or not hysterectomy is performed or transvaginal mesh is used at the time of repair; sexual activity status changes over time following prolapse surgery.

Secondhand smoke and functional impairments in older adults

BACKGROUND AND AIM: Secondhand smoke (SHS) is a risk factor of coronary heart disease, lung cancer, and stroke. Recent cross-sectional evidence suggests that it may also increase the risk of functional limitations, especially among older adults METHODS: We included data from 2828 community dwelling non-smoking older adults from the Seniors-Enrica-2 cohort (Madrid, Spain). Exposure to SHS was assessed by serum cotinine concentrations. At baseline (2017) and follow-up (2019), overall physical function was evaluated using the Spanish version of the physical component summary (PCS) of the 12-Item Short-Form Health questionnaire, lower-extremity performance with the Short Physical Performance Battery (SPPB), muscle weakness with a dynamometer, frailty with a Deficits Accumulation index (DAI), and disability in instrumental activities of daily living (IADL) with the Lawton-Brody questionnaire. Cross-sectional analyses were performed using linear and logistic regression models. Repeated measures models used robust standard error estimates to account for within-participant correlations induced by repeated measurements RESULTS:The median (IQR) concentrations of serum cotinine was 0.079 (0.035-0.175)ng/mL. After adjustment for potential confounders including sex, age, social class, civil status, tobacco exposure in the past, physical activity and BMI, and compared to participants with cotinine concentrations below the limit of detection (0.05ng/mL), those in the highest quartile of exposure (≥0.239ng/mL) showed baseline mean differences (95%CI) in the PCS, SPPB and muscle strength of -1.43 (-2.68,-0.18) points, -0.26 (-0.47,-0.06) points, and -1.21 (-1.92, -0.49) kilos; as well as a higher mean accumulation of deficits [2.62 (1.51,3.73)] and a higher odds of IADL limitations [1.38 (0.89, 2.14)]. In prospective analyses, the corresponding figures were -1.11 (-2.52,0.21) for PCS, -0.30 (-0.53,-0.07) for SPPB, -1.02 (-1.90,-0.13) for muscle weakness, 1.90 (0.64,3.16) for DAI and 1.15 (0.59,2.23) for IADL disability CONCLUSIONS:These findings suggest that exposure to SHS during old age may influence functional decline. If confirmed, more efforts would be needed to protect older adults from SHS KEYWORDS: Secondhand smoke, functional decline, ageing

P–332 Endometrium thickness is increased in gonadotropin stimulated IVF compared to unstimulated cycles, but this increase does not have a positive effect on pregnancy rate

Abstract Study question Is endometrial growth and endometrial thickness different in controlled ovarian stimulation (COS)-IVF compared to unstimulated cycles and does this have an effect on pregnancy rates? Summary answer Endometrial growth dynamic is different and endometrium is thicker in COS-IVF but this does not have a positive effect on pregnancy and live birth rates. What is known already Endometrial growth and endometrial thickness are a function of duration and concentration of estradiol (E2) stimulation. Endometrial thickness &amp;lt;8mm is related with lower pregnancy rates in IVF treatments. It is commonly assumed that an increase of endometrial thickness by increasing estrogen stimulation could have a positive effect on pregnancy rate. However, such a relationship has never been systematically analysed. Natural Cycle IVF (NC-IVF) is an ideal model to analyse the effect of high dose gonadotropin stimulation on several parameters such as thickness of endometrium and pregnancy rate. Study design, size, duration Retrospective single center, University based study including 235 COS-IVF and 616 NC-IVF cycles from 2015 to 2019. Polyfollicular COS-IVF cycles were only analysed until 09 2017 as embryo selection was introduced in Switzerland afterwards. Limiting the analysis to cycles without embryo selection enabled us to compare embryos derived from cIVF and NC-IVF. 1550 endometrial and 1068 E2 measurements were included in the analysis. Participants/materials, setting, methods Mean female age at the time when the cycles were performed was in NC-IVF 35.8±3.9y and in COS-IVF 34.9±4.2y (maximum 42y). Each woman performed on average 1.96±1.45 IVF cycles. Endometrial thickness and E2 serum concentrations were evaluated daily between day –4 and –2 (0=day of aspiration). Pregnancy and live birth rate were evaluated per transferred embryo. Statistically, student test and a repeated measure model and a logistic regression model both adjusted for age were used. Main results and the role of chance Endometrial thickness was different in COS-IVF and NC-IVF. At each time point endometrial thickness was found to be higher in COS-IVF compared to NC-IVF (p &amp;lt; 0.001 on days –4,–3, and –2). On day –2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ±2.05mm in COS-IVF and 8.12 ±1.66mm in NC-IVF. Endometrial growth dynamic was also different in COS-IVF and NC-IVF. Endometrial thickness increased significantly faster in NC-IVF cycles (0.58mm/day [0.43,0.73]) than in cIVF cycles (0.22mm/day [–0.12, 0.55], Pval= 0.034). The increase of endometrial thickness per day was less pronounced if E2 concentrations were high (–0.19 [–0.34, 0.05]). Therefore it can be assumed that the observed differences in growth dynamics in both treatments are caused by differences in E2. Increased endometrial thickness in COS-IVF was not associated with higher success rate. There was no significant effect of endometrium thickness on pregnancy (Pval=0.318) and Live birth rate (Pval=0.461). Limitations, reasons for caution Pregnancy and live birth rates might be affected by more than just endometrial thickness. The study was only based on the thickness of the endometrium but not on its ultrasound pattern. Wider implications of the findings: Postponing the aspiration to allow endometrium to further proliferate has only a limited effect in COS-IVF. Increasing gonadotropin stimulation dosage just to increase endometrial thickness is not a feasible strategy to improve pregnancy rate. The need to apply high dosages of estrogen supplementation in thawing cycles need to be questioned. Trial registration number “not applicable”

Prediction of corneal graft rejection using central endothelium/Descemet\u2019s membrane complex thickness in high-risk corneal transplants

To determine whether measurements of Endothelium/Descemet complex thickness (En/DMT) are of predictive value for corneal graft rejection after high-risk corneal transplantation, we conducted this prospective, single-center, observational case series including sixty eyes (60 patients) at high risk for corneal graft rejection (GR) because of previous immunologic graft failure or having at least two quadrants of stromal vascularization. Patients underwent corneal transplant. At 1st, 3rd, 6th, 9th, and 12th postoperative month, HD-OCT imaging of the cornea was performed, and the corneal status was determined clinically at each visit by a masked cornea specialist. Custom-built segmentation tomography algorithm was used to measure the central En/DMT. Relationships between baseline factors and En/DMT were explored. Time dependent covariate Cox survival regression was used to assess the effect of post-operative En/DMT changes during follow up. A longitudinal repeated measures model was used to assess the relationship between En/DMT and graft status. Outcome measures included graft rejection, central Endothelium/Descemet’s complex thickness, and central corneal thickness (CCT). In patients with GR (35%), the central En/DMT increased significantly 5.3 months (95% CI: 2, 11) prior to the clinical diagnosis of GR, while it remained stable in patients without GR. During the 1-year follow up, the rejected grafts have higher mean pre-rejection En/DMTs (p = 0.01), compared to CCTs (p = 0.7). For En/DMT ≥ 18 µm cut-off (at any pre-rejection visit), the Cox proportional hazard ratio was 6.89 (95% CI: 2.03, 23.4; p = 0.002), and it increased to 9.91 (95% CI: 3.32, 29.6; p < 0.001) with a ≥ 19 µm cut-off. In high-risk corneal transplants, the increase in En/DMT allowed predicting rejection prior to the clinical diagnosis.