PERINATAL CENTRILOBULAR HEPATIC NECROSIS IN GIANT PANDAS (AILUROPODA MELANOLEUCA): A RETROSPECTIVE STUDY.

Between 1983 and 2012, six giant panda cubs (Ailuropoda melanoleuca) born at a zoological institution were stillborn or died between the ages of 3 and 200 h. Two of the six cubs had panhepatic centrilobular hepatic necrosis (CHN), granulocytic extramedullary hematopoiesis (GEM), positive liver culture for Staphylococcus species, and terminal liver failure. Another low-weight cub was administered oxygen therapy immediately after birth and developed hyaline membranes in air spaces and hepatic necrosis restricted to the hilar region. A retrospective analysis of liver and lung lesions, pulmonary microanatomy, blood-gas barrier ultrastructure, and hepatic myofibroblast proliferation was conducted on the six cubs. Neonates with CHN had concurrent severe periportal GEM accompanied by severe myofibroblast proliferation. The pulmonary blood-gas barrier was markedly increased in one cub with CHN. Developmentally, the lungs of all but one cub were at the late saccular stage, and the lowest-weight cub was in early saccular stage, consistent with immaturity, and had pneumonia comparable to neonatal respiratory distress syndrome (RDS). Stage of lung development was eliminated as the primary factor leading to CHN. The pathogenesis of CHN in these neonates is proposed to be transformation of hepatic stellate cells to myofibroblasts initiating blockage and microvascular constriction of hepatic sinusoids, resulting in insufficient perfusion and cellular hypoxia of hepatocytes surrounding central veins in acinar zone 3.

A randomized feasibility pilot trial of a financial incentives intervention for dietary self-monitoring and weight loss in adults with obesity.

Financial incentives could be used to improve adherence to behavioral weight loss interventions, increasing their effectiveness. This Phase IIb randomized pilot study evaluated the feasibility and acceptability of a study protocol for providing financial incentives for dietary self-monitoring and/or weight loss. Community-dwelling adults with obesity were enrolled in a 24 week, group-based weight loss program. Participants were randomized in a 2 × 2 factorial design to receive financial incentives for both dietary self-monitoring and weekly weight loss, just one, or neither. Participants could earn up to $300, evolving from fixed weekly payments to intermittent, variable payments. The notice of reward was provided by text message. The study was conducted in three successive cohorts to evaluate study procedure changes, including dietary approach, recruitment and retention strategies, text messaging, and incentives. Descriptive statistics calculated separately for each cohort described study performance relative to predefined targets for recruitment, including minority representation; retention; adherence; and weight loss. Acceptability was assessed via postintervention qualitative interviews. In Cohort 1 (n = 34), a low-carbohydrate diet was used. Recruitment, retention, adherence, and weight loss were adequate, but minority representation was not. For Cohort 2 (n = 31), employing an additional recruitment method and switching to a reduced-calorie diet yielded adequate recruitment, minority representation, retention, and adherence but less weight loss. Returning to a low-carbohydrate diet in Cohort 3 (n = 28) yielded recruitment, minority representation, retention, adherence, and weight loss similar to Cohort 2. Participant feedback informed changes to text message timing and content and incentive amount. Through successive cohorts, we optimized recruitment and retention strategies and text messaging. An adequately powered trial is warranted to evaluate the efficacy of these incentive structures for reducing weight. The trial registration number is NCT02691260.

Opioid Prescribing in the 2016 Medicare Fee-for-Service Population.

BACKGROUND AND OBJECTIVES: Opioid use and misuse are prevalent and remain a national crisis. This study identified beneficiary characteristics associated with filling opioid prescriptions, variation in opioid dosing, and opioid use with average daily doses (ADDs) equal to 120 morphine milligram equivalents (MMEs) or more in the 100% Medicare fee-for-service (FFS) population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In a cohort of FFS beneficiaries with 12 months of Medicare Part D coverage in 2016, we examined patient factors associated with filling an opioid prescription (n = 20,880,490) and variation in ADDs (n = 7,325,031) in a two-part model. Among those filling opioids, we also examined the probability of ADD equal to 120 MMEs or more via logistic regression. RESULTS: About 35% of FFS beneficiaries had one or more opioid prescription fills in 2016 and 1.5% had ADDs equal to 120 MMEs or more. Disability-eligible beneficiaries and beneficiaries with multiple chronic conditions were more likely to fill opioids, to have higher ADDs or were more likely to have ADD equal to 120 MMEs or more. Beneficiaries with chronic obstructive pulmonary disease (COPD) were more likely to fill opioids (odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.46-1.47), have higher ADDs (rate ratio = 1.06, 95% CI = 1.06-1.06) when filled and were more likely to have ADD equal to 120 MMEs or more (OR = 1.23, 95% CI = 1.21-1.24). Finally, black and Hispanic beneficiaries were less likely to fill opioids, had lower overall doses and were less likely to have ADDs equal to 120 MMEs or more compared to white beneficiaries. CONCLUSION: Several beneficiary subgroups have underappreciated risk of adverse events associated with ADD equal to 120 MMEs or more that may benefit from opioid optimization interventions that balance pain management and adverse event risk, especially beneficiaries with COPD who are at risk for respiratory depression.

Lab-based and diagnosis-based chronic kidney disease recognition and staging concordance.

BACKGROUND: Chronic kidney disease (CKD) is often under-recognized and poorly documented via diagnoses, but the extent of under-recognition is not well understood among Medicare beneficiaries. The current study used claims-based diagnosis and lab data to examine patient factors associated with clinically recognized CKD and CKD stage concordance between claims- and lab-based sources in a cohort of Medicare beneficiaries. METHODS: In a cohort of fee-for-service (FFS) beneficiaries with CKD based on 2011 labs, we examined the proportion with clinically recognized CKD via diagnoses and factors associated with clinical recognition in logistic regression. In the subset of beneficiaries with CKD stage identified from both labs and diagnoses, we examined concordance in CKD stage from both sources, and factors independently associated with CKD stage concordance in logistic regression. RESULTS: Among the subset of 206,036 beneficiaries with lab-based CKD, only 11.8% (n = 24,286) had clinically recognized CKD via diagnoses. Clinical recognition was more likely for beneficiaries who had higher CKD stages, were non-elderly, were Hispanic or non-Hispanic Black, lived in core metropolitan areas, had multiple chronic conditions or outpatient visits in 2010, or saw a nephrologist. In the subset of 18,749 beneficiaries with CKD stage identified from both labs and diagnoses, 70.0% had concordant CKD stage, which was more likely if beneficiaries were older adults, male, lived in micropolitan areas instead of non-core areas, or saw a nephrologist. CONCLUSIONS: There is significant under-diagnosis of CKD in Medicare FFS beneficiaries, which can be addressed with the availability of lab results.

A novel curriculum to train physician assistant students how to write effective discharge summaries.

Background: Physician assistants (PAs) are an integral part of inpatient care teams, but many PAs do not receive formal education on authoring discharge summaries. High-quality discharge summaries can mitigate patient risk during transitions of care by improving inter-provider communication. Objective: To understand the current state of discharge summary education at our institution, and describe a novel curriculum to teach PA students to write effective discharge summaries. Design: Students completed a pre-survey to assess both knowledge and comfort levels regarding discharge summaries. They wrote a discharge summary and received feedback from two evaluators, an inpatient provider (IPP) familiar with the described patient and a simulated primary care provider (PCP). Students completed a post-survey reassessing knowledge and comfort. Results: Prior to instituting this curriculum, the majority of students (92.9%) reported rarely or never receiving feedback on discharge summaries. Eighty-four of 88 (95.5%) eligible students participated. There was discordance between IPP and simulated PCP feedback on their assessment of the quality of discharge summaries; simulated PCPs gave significantly lower global quality ratings (7.9 versus 8.5 out of 10, p = 0.006). Key elements were missing from >10% of discharge summaries. Student response was favorable. Conclusion: Clinically relevant deficiencies were common in students' discharge summaries, highlighting the need for earlier, structured training. IPPs and simulated PCPs gave discordant feedback, emphasizing differing needs of different providers during transitions of care. This novel curriculum improved students' knowledge and confidence.

Dietary Phosphorus and Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.

BACKGROUND: Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns. METHODS: Our study included 973 African American adults enrolled in the Jackson Heart Study (2000-2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension. RESULTS: There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping. CONCLUSIONS: These data do not support a role for higher phosphorus intake and higher BP in African Americans.

HEART Failure? Episodes of Missed Major Cardiac Events When Applying the HEART Pathway to an Observation Unit Population.

OBJECTIVE: The HEART Pathway risk prediction tool (HEART score plus serial troponin measures at 0 and 3 hours post-presentation) is used to identify low-risk patients with chest pain who may qualify for safe, early discharge. We calculated the percentage of patients in our observation unit that qualified as low risk using HEART Pathway, as well as their associated outcomes. METHODS: We retrospectively reviewed charts on 966 consecutive patients admitted to our observation unit for chest pain (January 2015 to February 2016); HEART Pathway scores were retrospectively calculated and serial cardiac troponin values logged. The primary outcome was 42-day major adverse cardiac events (MACE), including acute myocardial infarction, urgent revascularization, and all-cause death. RESULTS: The patients' mean age was 59, 42% were male, 46% white, and 68 (7.7%) had MACE. HEART Pathway defined 384 patients as low risk (39.8%) and eligible for early discharge. Applying HEART Pathway would have missed 1.2% of patients with MACE; however, all adverse cardiac events occurred in patients with a HEART Pathway score of 3 (4 of 193, 2.1%) and none in those with a HEART Pathway score ≤2 (0 of 134). CONCLUSIONS: While the HEART Pathway identifies a pooled population at low risk for MACE, risk is not homogenous within this population. Patients with a score of 3 may have higher risk of 42-day MACE that may be unacceptable to some providers, while scores ≤2 saw no events. Caution is advised for those with HEART Pathway score of 3 until more data is available to accurately estimate risk.

Assessing the Impact of an Order Panel Utilizing Weight-Based Insulin and Standardized Monitoring of Blood Glucose for Patients With Hyperkalemia.

Intravenous insulin with glucose is used in urgent treatment for hyperkalemia but has a significant risk of hypoglycemia. The authors developed an order panel within the electronic health record system that utilizes weight-based insulin dosing and standardized blood glucose monitoring to reduce hypoglycemia. As initial evaluation of this protocol, the authors retrospectively compared potassium and blood glucose lowering in patients treated with the weight-based (0.1 units/kg) insulin order panel (n = 195) with those given insulin based on provider judgment (n = 69). Serum potassium lowering did not differ between groups and there was no relationship between dose of insulin and amount of potassium lowering. There was a difference in hypoglycemia rates between groups ( P = .049), with fewer severe hypoglycemic events in the panel (2.56%) than in the non-panel group (10.14%). These data suggest weight-based insulin dosing is equally effective for lowering serum potassium and may lower risk of severe hypoglycemia.

Study protocol for Log2Lose: A feasibility randomized controlled trial to evaluate financial incentives for dietary self-monitoring and interim weight loss in adults with obesity.

The obesity epidemic has negative physical, psychological, and financial consequences. Despite the existence of effective behavioral weight loss interventions, many individuals do not achieve adequate weight loss, and most regain lost weight in the year following intervention. We report the rationale and design for a 2×2 factorial study that involves financial incentives for dietary self-monitoring (yes vs. no) and/or interim weight loss (yes vs. no). Outpatients with obesity participate in a 24-week, group-based weight loss intervention. All participants are asked to record their daily dietary and liquid intake on a smartphone application (app) and to weigh themselves daily at home on a study-provided cellular scale. An innovative information technology (IT) solution collates dietary data from the app and weight from the scale. Using these data, an algorithm classifies participants weekly according to whether they met their group's criteria to receive a cash reward ranging from $0 to $30 for dietary self-monitoring and/or interim weight loss. Notice of the reward is provided via text message, and credit is uploaded to a gift card. This pilot study will provide information on the feasibility of using this novel IT solution to provide variable-ratio financial incentives in real time via its effects on recruitment, intervention adherence, retention, and cost. This study will provide the foundation for a comprehensive, adequately-powered, randomized controlled trial to promote short-term weight loss and long-term weight maintenance. If efficacious, this approach could reduce the prevalence, adverse outcomes, and costs of obesity for millions of Americans. Clinicaltrials.gov registration: NCT02691260.

Prevalence of diabetic retinopathy within a national diabetic retinopathy screening service.

AIMS: Determine the prevalence and severity of diabetic retinopathy (DR) and risk factors in a large community based screening programme, in order to accurately estimate the future burden of this specific and debilitating complication of diabetes. METHODS: A cross-sectional analysis of 91,393 persons with diabetes, 5003 type 1 diabetes and 86,390 type 2 diabetes, at their first screening by the community based National Diabetic Retinopathy Screening Service for Wales from 2005 to 2009. Image capture used 2×45° digital images per eye following mydriasis, classified by qualified retinal graders with final grading based on the worst eye. RESULTS: The prevalence of any DR and sight-threatening DR in those with type 1 diabetes was 56.0% and 11.2%, respectively, and in type 2 diabetes was 30.3% and 2.9%, respectively. The presence of DR, non-sight-threatening and sight-threatening, was strongly associated with increasing duration of diabetes for either type 1 or type 2 diabetes and also associated with insulin therapy in those with type 2 diabetes. CONCLUSIONS: Prevalence of DR within the largest reported community-based, quality assured, DR screening programme, was higher in persons with type 1 diabetes; however, the major burden is represented by type 2 diabetes which is 94% of the screened population.

Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography.

PURPOSE: To map choroidal (ChT) and retinal thickness (RT) in healthy subjects and patients with diabetes with and without maculopathy using three dimensional 1060-nm optical coherence tomography (3D-1060nm-OCT). METHODS: Sixty-three eyes from 42 diabetic subjects (41-82 years of age; 11 females) grouped according to a custom scheme using Early Treatment Diabetic Retinopathy Study definitions for pathology within 1 disc-diameter of fovea (without pathology [NDR], microaneurysms [M1], exudates [M2], clinically significant macular edema [CSME]) and 16 eyes from 16 healthy age matched subjects (38-79 years of age; 11 females) were imaged by 3D-1060nm-OCT performed over a 36° × 36° field of view. Axial length, 45° fundus photographs, body mass index, plasma glucose, and blood pressure measurements were recorded. The ChT at the subfoveal location and ChT maps between RPE and the choroidal-scleral interface were generated and statistically analyzed. RESULTS: RT maps show thinning in the NDR group but an increase in thickness with increasing maculopathy in the temporal and central regions (unpaired t-test; P < 0.05). ChT mapping of all diabetic patients revealed central and inferior thinning compared to healthy eyes (unpaired t-test; P < 0.001). Subfoveal ChT (mean ± SD) for healthy eyes was 327 ± 74 µm, which was significantly thicker than all diabetic groups (214 ± 55 µm for NDR, 208 ± 49 µm for M1, 205 ± 54 µm for M2, and 211 ± 76 µm for CSME (ANOVA P < 0.001; Tukey P < 0.001). CONCLUSIONS: 3D-1060nm-OCT has shown that the central choroid is thinner in all type 2 diabetic eyes regardless of disease stage. The choroidal thinning may exceed the magnitude of possible choriocapillaris atrophy. In contrast to the conventional assessment of pathologic thickness change in several locations, thickness maps allow investigation of the choroid over the extent of affected areas.

Modern pathology methods for neural investigations.

This session at the 2010 joint symposium of the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP) explored modern neuropathology methods for assessing the neurotoxicologic potential of xenobiotics. Conventional techniques to optimally prepare and evaluate the central and peripheral neural tissues while minimizing artifact were reviewed, and optimal schemes were set forth for evaluation of the nervous system during both routine (i.e., general toxicity) studies and enhanced (i.e., specialized neurotoxicity) studies. Stereology was introduced as the most appropriate means of examining the possible impact of toxicants on neural cell numbers. A focused discussion on brain sampling took place among a panel of expert neuroscientists (anatomists and pathologists) and the audience regarding the proper balance between sufficient sampling and cost- and time-effectiveness of the analysis. No consensus was reached on section orientation (coronal sections of both sides vs. a parasagittal longitudinal section with several unilateral hemisections from the contralateral side), but most panelists favored sampling at least 8 sections (or approximately double to triple the current complement) in routine toxicity studies.

Cortical visual impairment in hypomelanosis of Ito.

Hypomelanosis of Ito is a multisystem disorder that is thought to be due to chromosomal mosaicism. The authors report a case of cortical visual impairment in an infant diagnosed as having hypomelanosis of Ito. Cortical dysplasia was evident on magnetic resonance imaging and its presence in key areas of the visual pathway may explain the patient's cortical visual impairment.

Delayed treatment with MLN519 reduces infarction and associated neurologic deficit caused by focal ischemic brain injury in rats via antiinflammatory mechanisms involving nuclear factor-kappaB activation, gliosis, and leukocyte infiltration.

Secondary brain injury due to ischemia includes the infiltration of leukocytes into the brain parenchyma mediated by activation of nuclear factor-kappaB (NF-kappaB), which is activated by proteasome degradation. Neuroprotection with the proteasome inhibitor MLN519 has previously been reported to decrease ischemic brain injury in rats. The authors used higher doses of MLN519 to evaluate the neuroprotection therapeutic window after 24 hours of brain injury in rats as correlated to proteasome levels, activated NF-kappaB immunoreactivity, and leukocyte infiltration. Male Sprague-Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO) and recovery. MLN519 or vehicle was administered after injury with a single injection given in delayed increments of 2 hours (i.e., 4, 6, or 8 hours after MCAO). Treatment with MLN519 up to 6 hours after MCAO (4 hours after reperfusion) effectively reduced neuronal and astrocytic degeneration, decreased cortical infarct volume, and increased neurologic recovery. These effects were related to >80% reductions in blood proteasome levels, reduced neutrophil infiltration, and a decrease in activated NF-kappaB immunoreactivity. This improved neuroprotection profile and antiinflammatory effect of MLN519 provides an exciting avenue for potential treatment of focal ischemic brain injury in humans.

Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury.

Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines, some of which are regulated by the nuclear transcription factor NF-kappaB. In this study the authors examined mRNA expression levels for several important genes associated with inflammation at five time points (3, 6, 12, 24, and 72 hours) after transient middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. A sensitive and quantitative technique (TaqMan real-time QRT-PCR) was used to simultaneously measure mRNA levels for key cell adhesion molecules and inflammatory cytokines. Gene expression increased significantly in the injured hemisphere for interleukin (IL)-1beta (12-fold increase at 24 hours), IL-6 (25-fold increase at 6 hours) and ICAM-1 (4-fold increase at 24 hours), and the interhemispheric differences for these genes were significant for every time point examined (P < 0.05 for all values). Tumor necrosis factor-alpha mRNA was upregulated in the injured versus uninjured hemisphere from 3 to 24 hours (5-fold increase at 6 hours), while E-selectin showed a significant increase in mRNA levels from 6 to 24 hours after MCAO (10-fold increase at 6 hours) (P < 0.05 for all values). VCAM-1 mRNA levels did not respond differentially to injury at any time point between the two brain hemispheres. At all time points examined, activated NF-kappaB immunoreactivity was observed in cells throughout the infarct-damaged tissue. These results are consistent with the proinflammatory properties of the induced molecules, which are involved in the initiation of the inflammatory cascade, and may thus contribute to secondary cellular responses that lead to further brain damage.