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Summary: Background: Hypoglycaemia from diabetes treatment causes morbidity and lower quality of life, and prevention should be routinely addressed in clinical visits. Methods: This mixed methods study evaluated how primary care providers (PCPs) assess for and prevent hypoglycaemia by analyzing audio-recorded visits from five Veterans Affairs medical centres in the US. Two investigators independently coded visit dialogue to classify discussions of hypoglycaemia history, anticipatory guidance, and adjustments to hypoglycaemia-causing medications according to diabetes guidelines. Findings: There were 242 patients (one PCP visit per patient) and 49 PCPs. Two thirds of patients were treated with insulin and 40% with sulfonylureas. Hypoglycaemia history was discussed in 78/242 visits (32%). PCPs provided hypoglycaemia anticipatory guidance in 50 visits (21%) that focused on holding diabetes medications while fasting and carrying glucose tabs; avoiding driving and glucagon were not discussed. Hypoglycaemia-causing medications were de-intensified or adjusted more often (p

Background and Aims: Thrombocytopenia is present in up to 76% of patients with chronic liver disease, and lower platelet counts (PCs) are associated with greater severity of portal hypertension. In this study, we assess the relationship of PC in patients with a clinical diagnosis of severe alcoholic hepatitis (SAH) with clinical severity and response to corticosteroid (CS) therapy. Methods: Clinical characteristics, treatment, and hospital outcomes for patients admitted with SAH were analyzed from an electronic health record system. Patients were categorized based on admission PC (k/uL) into 5 categories:

Objective: Data on RW treatment patterns and outcomes in RRMM Pts who received at least one prior line of therapy (LoT) are lacking outside the US and Europe. This study evaluated RW clinical characteristics, treatment patterns, and outcomes among Turkish Pts who received at least one prior MM-specific therapy. Methodology: This retrospective chart review included RRMM Pts who had received at least one prior LoT and initiated a second-line (2L) or third-line (3L) MM-specific treatment regimen between 01-Jan-2015 and 31-Dec-2020. Patients’ demographics and clinical characteristics, treatment patterns, and overall survival (OS) were evaluated. Results: Of the 107 RRMM Pts initiating 2L treatment, 91.6% experienced symptomatic disease [prominent symptoms: anemia (71.0%); bone lesions (53.3%)]. Table 1 presents other clinical and demographic characteristics. Bortezomib (BOR)-based regimens were most used in first-line (1L) regardless of stem-cell transplant (SCT) status (SCT induction: 68.7%; non-SCT: 79.5%), and lenalidomide (LEN-based regimens were used as 1L maintenance (40.3%). LEN-free regimens were used in 58.1% (2L) and 35.6% (3L) of Pts, with DVd (29.5%) and DRd (19.5%) being the most utilized regimens in 2L and 3L, respectively (Fig. 1). In total, 53.1% were LEN-retreated and 30.8% were LEN-refractory. The median (interquartile range) duration of treatment on 2L [7.0 (6.0, 10.5) months] and 3L [7.1 (6.0, 14.0) months] was short (Table 2). After 2L and 3L initiation, 57.9% and 25.6% of Pts had disease progression; median OS was 10.4 and 12.8 months, respectively (Table 3). Conclusion: BOR-based regimens were commonly utilized in 1L. LEN-based regimens were used as maintenance therapy in 1L and as retreatment in RRMM Pts. Newer therapies (Daratumumab- or Carfilzomib-based regimens) were utilized in 2L and 3L. The short duration of therapy, high disease progression rate, high LEN retreatment, and refractoriness rates indicate the need for new LEN-free regimens for treating RRMM Pts in Turkey.

Human Lyme disease–primarily caused by the bacterium Borrelia burgdorferi sensu stricto (s.s.) in North America–is the most common vector-borne disease in the United States. Research on risk mitigation strategies during the last three decades has emphasized methods to reduce densities of the primary vector in eastern North America, the blacklegged tick (Ixodes scapularis). Controlling white-tailed deer populations has been considered a potential method for reducing tick densities, as white-tailed deer are important hosts for blacklegged tick reproduction. However, the feasibility and efficacy of white-tailed deer management to impact acarological risk of encountering infected ticks (namely, density of host-seeking infected nymphs; DIN) is unclear. We investigated the effect of white-tailed deer density and management on the density of host-seeking nymphs and B. burgdorferi s.s. infection prevalence using surveillance data from eight national parks and park regions in the eastern United States from 2014–2022. We found that deer density was significantly positively correlated with the density of nymphs (nymph density increased by 49% with a 1 standard deviation increase in deer density) but was not strongly correlated with the prevalence of B. burgdorferi s.s. infection in nymphal ticks. Further, while white-tailed deer reduction efforts were followed by a decrease in the density of I. scapularis nymphs in parks, deer removal had variable effects on B. burgdorferi s.s. infection prevalence, with some parks experiencing slight declines and others slight increases in prevalence. Our findings suggest that managing white-tailed deer densities alone may not be effective in reducing DIN in all situations but may be a useful tool when implemented in integrated management regimes.

Therapeutic Area: ASCVD/CVD Risk Reduction Background: Elevated lipoprotein(a) [Lp(a)] is the most common inherited dyslipidemia leading to an increased risk of atherosclerotic cardiovascular disease (ASCVD). Several cohort studies have reported elevated Lp(a) prevalence in the general population; however, there is a paucity of data in those with established ASCVD. This sub-analysis of the Lp(a)HERITAGE study (NCT03887520) assessed Lp(a) levels in United States (US) participants with ASCVD, stratified by race, ethnicity, and sex. Methods: This cross-sectional study assessed the prevalence of elevated Lp(a) in adult participants (18–80 years of age) with a history of myocardial infarction or ischemic stroke ≥3 months to ≤10 years prior to enrollment (April 2019–July 2021) or symptomatic peripheral artery disease, across 192 US sites. Lp(a) and low-density lipid-cholesterol (LDL-C) levels were obtained using US central laboratory or historical data. Results: In total, 8,295 US participants were enrolled. The sub-analysis included 7,679 participants with Lp(a) measured in nmol/L, of which 66.4% were male, 80.5% were White, 16.9% were Black, and 8.0% had Hispanic ethnicity. Compared with the overall population, median Lp(a) was >2.5-fold higher in Black participants (132.0 vs 52.1 nmol/L) and was 21.8% lower in Hispanic participants (40.7 vs 52.1 nmol/L); in females, median Lp(a) levels were >1.5-fold higher than in male participants (69.4 vs 45.6 nmol/L) (Table). Overall, 33.3% of participants had Lp(a) ≥125 nmol/L. Prevalence of Lp(a) ≥125 nmol/L was highest among Black participants (52.0%) and lowest among Hispanic participants (25.6%); a greater proportion of females had Lp(a) ≥125 nmol/L compared with males (38.9% vs 30.4%) (Table). Conclusions: In the Lp(a)HERITAGE study, 33.3% of US participants with established ASCVD had Lp(a) levels ≥125 nmol/L. Compared with the overall population, the proportion of patients with Lp(a) ≥125 nmol/L was higher in Black (52.0%) and female (38.9%) participants and was lower in Hispanic participants (25.6%). These findings support more aggressive Lp(a) screening strategies among patients with established ASCVD, particularly female or Black patients. Furthermore, elevated Lp(a) levels can be used to inform the intensification of lifestyle and other risk factor management in clinical practice and may have implications for potential future therapies targeting Lp(a).

Objective: To test an intervention designed to improve patient engagement in telehealth visits by encouraging patients to use active communication behaviors. Methods: US Veterans with type 2 diabetes mellitus receiving primary care using telehealth were randomized 1:1 to receive both a pre-visit educational video and pamphlet (intervention) or pamphlet alone (control) prior to their scheduled telehealth visit. Data were collected before and after the intervention from the medical record and at telephone interviews (questionnaires). Analyses compared the intervention and control groups using bivariate statistics and multiple regression. Results: There were no statistically significant differences in baseline Hemoglobin A1c (HbA1c) between intervention and control groups (P > 0.05). Patient's ratings of physicians' communication and post-visit empathy were higher (P ≤ 0.05) in the intervention group than control group and after adjusting for baseline values the intervention group reported higher scores on post-visit therapeutic alliance with the provider and higher patient engagement, compared with the control group, P = 0.01 and P = 0.04, respectively, but post-visit HbA1c was not statistically different. Conclusions: The educational video was useful as pre-visit preparation for patients prior to a primary care telehealth visit. Innovation: This study showed the efficacy of a pre-visit video to improve patient engagement and therapeutic alliance after telehealth visits.ClinicalTrials.gov Identifier: NCT02522494

Background: Medication regimens for Parkinson’s disease (PD) may change as the disease progresses, symptoms fluctuate, or medication-related adverse events occur. This study evaluated treatment trends by observation year for patients initially receiving monotherapy with levodopa and a peripheral dopa decarboxylase inhibitor (PDDI). Methods: In this retrospective chart review, therapy changes were evaluated for patients across the US diagnosed with PD on or before 6/30/2014 who initially received levodopa-PDDI monotherapy. Index date was the first clinic visit. Post-index was any time between the first 31 days after index and study end (6/30/2019). Index Hoehn-Yahr (H-Y) score and medication changes were also analyzed by index low (

Background: Parkinson’s disease (PD) management seeks to balance the benefits and harms of current medications and evolves as the disease progresses. The natural history of PD and associated patterns of treatment change were analyzed to identify unmet needs in treatment of PD symptoms. Methods: Medical charts of patients from clinics across the US diagnosed on or before June 30th, 2014 were retrospectively reviewed. Index date was the first clinic visit, and the post-index period was through study end (June 30th, 2019). Outcomes included the frequency of therapy changes in the post-index period, reasons for therapy change, and adverse events (AE). Results: Patients (n = 203) at index were receiving levodopa-peripheral dopa decarboxylase inhibitor (PDDI) monotherapy (47%), dopaminergic agonist (DA) monotherapy (15%), monoamine oxidase B inhibitor (MAOBI) monotherapy (14%), or combination therapies. The percentage of patients in Hoehn-Yahr disease Stage 1–2 was 52% at index and 20% by the end of the study. Frequencies of motor, non-motor, and neuropsychiatric symptoms increased during the enrollment. Levodopa-PDDI monotherapy and levodopa-PDDI + MAOBI had the lowest rates of therapy changes. Symptom relapse was the most common reason for dose escalation, add-on, and dose reduction, whereas AEs were the most common reason for discontinuation and switching. Dose escalation, add-on, and forward switch were most likely to occur in the first 6 months of treatment. Conclusions: Therapy changes during the study period reflected the challenging and evolving management of PD as the disease progresses. New or add-on symptomatic treatments are needed that are well-tolerated and able to control PD symptoms.

Great Smoky Mountains National Park (GRSM) is the most visited National Park in the United States and has the highest levels of biodiversity of any park unit. It is a relatively small park (∼210,433 ha), but topographically complex, with an elevational range of 1757 m. The Park has historically been subject to elevated levels of pollutants, including sulfur dioxide (SO2), ozone (O3), and nitrogen oxides (NOx). Ozone trends are analyzed from 1989 to 2016 for six monitoring sites in and adjacent to GRSM and ranging in elevation from 564 m to 2030 m. Low-elevation sites have minimum O3 concentrations in early morning and maximum concentrations in mid-to late afternoon. High-elevation sites have flatter profiles, smaller diurnal ranges, and maxima that occur in early evening or at night. The W12624-h exposure index increases with elevation up to 823 m, after which it plateaus. W12624- h exposures increased between the years 1989–∼2002, and have substantially decreased afterwards. The highest 1-h concentration ever recorded in the Park was 135 ppb, which occurred on 25 August 1998. At most sites the maximum 3-month W12624-h exposures have shifted from mid-summer to spring (Apr–Jun). Decreases in exposure result primarily from reduction of hourly averaged O3 concentrations ≥ 60 ppb. Ozone episodes (3 or more consecutive hours when O3 ≥ 60 ppb) have decreased in frequency, magnitude, and duration from 1999 to 2016. Decreases in W126 exposures are correlated with lowered NOx emissions from regional TVA power plants and appear to be a direct result of the State Implementation Plan (SIP) call associated with the Clean Air Act Amendments, resulting in the cleanest air in GRSM over the period of record. Lower cumulative W126 O3 exposures and reduction in high O3 concentrations appear to be having beneficial effects on the vegetation within the Park. Keywords: W126 exposure index, Trends, Elevation, Vegetation

Parkinson׳s disease (PD), the second most common neurodegenerative disorder, affects roughly 7–10 million people worldwide. A wide array of research has suggested that PD has a mitochondrial component and that mitochondrial dysfunction occurs well in advance of the clinical manifestation of the disease. Previous work by our lab has categorized the mitochondrial disorder associated with Parkinson׳s disease in a PINK1 knockout rat model. This model develops Parkinson׳s disease in a spontaneous, predictable manner. Our findings demonstrated PINK1-deficient rats at 4 months of age had mitochondrial proteomic and functional abnormalities before the onset of Parkinsonian symptoms (6 months) such as the movement disorder, loss of midbrain dopaminergic neurons, or the progressive degeneration present at 9 months. With this in mind, our group investigated the PINK1 knockout genetic rat model at postnatal day 10 to determine if the observed alterations at 4 months were present at an earlier time point. Using a proteomic analysis of brain mitochondria, we identified significant mitochondrial proteomic alterations in the absence of mitochondrial functional changes suggesting the observed alterations are part of the mitochondrial pathways leading to PD. Specifically, we identified differentially expressed proteins in the PINK1 knockout rat involved in glycolysis, the tricarboxylic acid cycle, and fatty acid metabolism demonstrating abnormalities occur well in advance of the manifestation of clinical symptoms. Additionally, 13 of the differentially expressed proteins have been previously identified in older PINK1 knockout animals as differentially regulated suggesting these proteins may be viable markers of the PD pathology, and further, the abnormally regulated pathways could be targeted for therapeutic interventions. All raw data can be found in Supplementary Table 1.