Peripheral Administration of Selective Glycine Transporter-2 Inhibitor, Oleoyl-D-Lysine, Reverses Chronic Neuropathic Pain but Not Acute or Inflammatory Pain in Male Mice.

Aberrations in spinal glycinergic signaling are a feature of pain chronification. Normalizing these changes by inhibiting glycine transporter (GlyT)-2 is a promising treatment strategy. However, existing GlyT2 inhibitors (e.g., ORG25543) are limited by narrow therapeutic windows and severe dose-limiting side effects, such as convulsions, and are therefore poor candidates for clinical development. Here, intraperitoneally administered oleoyl-D-lysine, a lipid-based GlyT2 inhibitor, was characterized in mouse models of acute (hot plate), inflammatory (complete Freund's adjuvant), and chronic neuropathic (chronic constriction injury) pain. Side effects were also assessed on a numerical rating score, convulsions score, for motor incoordination (rotarod), and for respiratory depression (whole body plethysmography). Oleoyl-D-lysine produced near complete antiallodynia for chronic neuropathic pain, but no antiallodynia/analgesia in inflammatory or acute pain. No side effects were seen at the peak analgesic dose, 30 mg/kg. Mild side effects were observed at the highest dose, 100 mg/kg, on the numerical rating score, but no convulsions. These results contrasted markedly with ORG25543, which reached less than 50% reduction in allodynia score only at the lethal/near-lethal dose of 50 mg/kg. At this dose, ORG25543 caused maximal side effects on the numerical rating score and severe convulsions. Oleoyl-D-lysine (30 mg/kg) did not cause any respiratory depression, a problematic side effect of opiates. These results show the safe and effective reversal of neuropathic pain in mice by oleoyl-D-lysine and provide evidence for a distinct role of glycine in chronic pain over acute or short-term pain conditions. SIGNIFICANCE STATEMENT: Partially inhibiting glycine transporter (GlyT)-2 can alleviate chronic pain by restoring lost glycinergic function. Novel lipid-based GlyT2 inhibitor ol-D-lys is safe and effective in alleviating neuropathic pain, but not inflammatory or acute pain. Clinical application of GlyT2 inhibitors may be better suited to chronic neuropathic pain over other pain aetiologies.

Establishing and maintaining social connectivity: An understanding of the lived experiences of older adults residing in regional and rural communities.

OBJECTIVE: To better understand how to plan for an ageing demographic that resides in ever-changing community typologies. DESIGN: Semi-structured in-depth interviews. SETTING: Community settings in rural and regional towns in Queensland. PARTICIPANTS: Twenty-two people aged over 65 years living in regional and rural Australia. INTERVENTIONS: Qualitative study of social connectedness. MAIN OUTCOME MEASURE(S): Thematic qualitative analysis. RESULTS: Formal and informal social contact, through family, friends and social groups, was found to be important to the everyday lives of the participants. CONCLUSIONS: Social connections for older adults are important in maintaining independence and community engagement.

Postdischarge pharmacist medication reconciliation: impact on readmission rates and financial savings.

OBJECTIVE: To assess the impact of ambulatory clinical pharmacist medication therapy assessment and reconciliation for patients postdischarge in terms of hospital readmission rates, financial savings, and medication discrepancies. SETTING: Group Health Cooperative (Group Health) in Washington State, from September 2009 through February 2010. PRACTICE DESCRIPTION: Group Health is a nonprofit integrated group practice and health plan, operating 25 primary care medical centers and 5 specialty centers. Group Health's practice design is a patient-centered medical home model. PRACTICE INNOVATION: All patients identified as high risk for readmission were followed by Group Health care management. Patients in care management who received a phone call from a pharmacist 3 to 7 days postdischarge for medication therapy assessment and reconciliation were identified as the medication review group (n = 243). Patients who did not receive clinical pharmacist intervention were included in the comparison group (n = 251). MAIN OUTCOME MEASURES: Readmission rates, financial savings, and medication discrepancies. RESULTS: Patients who received medication therapy assessment and reconciliation had decreased readmission rates at 7, 14, and 30 days postdischarge, with statistical significance at 7 and 14 days. Medication review versus comparison readmission rates were as follows: 7 days: 0.8% vs. 4% ( P = 0.01); 14 days: 5% vs. 9% ( P = 0.04); and 30 days: 12% vs. 14% ( P = 0.29). Financial savings for Group Health per 100 patients who received medication reconciliation was an estimated $35,000, translating to more than $1,500,000 in savings annually. Of patients, 80% had at least one medication discrepancy upon discharge. CONCLUSION: Most literature on medication reconciliation evaluates inpatient processes, whereas data on medication reconciliation postdischarge are limited. Our data support the hypothesis that medication assessment and reconciliation by pharmacists 3 to 7 days postdischarge can decrease readmissions and provide cost savings.

Uncontrolled Arterial Bleeding in a Patient With Massive Right Calf Hematoma: A Case Report and a Review of the Literature.

A hematoma is a collection of pooled blood that can be confined to a space under the skin, tissue, or organ. It occurs due to injury to the vasculature arising from trauma, previous surgeries, or vascular defects. Anticoagulants can remarkably increase a patient's risk for hematoma formation. Most hematomas will resolve spontaneously over time, but there are certain instances where surgical intervention becomes necessary. We present a case of a 71-year-old female on anticoagulants who presented to the emergency department (ED) with an expanding hematoma on her right leg after a fall and had to undergo an emergency surgical evacuation. The etiology, appropriate management, and complications of hematomas will also be covered in this paper.

Cutaneous Metastases in Progressive Prostate Adenocarcinoma: A Case Report and Literature Review.

Prostate cancer has an indolent progression course and commonly metastasizes to the vertebrae bone and regional lymph nodes. We report a patient with prostate cancer who has developed cutaneous metastases in multiple regions, including the right infraclavicular and abdominal area, as well as the left supraclavicular region. It presented as isolated, prominent nodules that were microscopically proven to be of prostate adenocarcinoma when biopsied. This rare presentation is a marker of an advanced disease course with a poor prognosis in castrate-resistant prostate cancer. Thorough clinical examination to rule out metastasis from the prostate and other dermatological conditions is paramount as well as ensuring early detection and optimizing patient outcomes.

Thoracic endovascular repair of chronic type B aortic dissection: a systematic review.

BACKGROUND: At present, the optimal management strategy for chronic type B aortic dissection (CTBAD) remains unknown, as equipoise remains regarding medical management versus endovascular treatment versus open surgery. However, the results over recent years of thoracic endovascular aortic repair (TEVAR) in CTBAD appear promising. The aim of this systematic review was to provide a comprehensive analysis of the available data reporting outcomes and survival rates for TEVAR in CTBAD. METHODS: Electronic searches of six databases were performed from inception to April 2021. All studies reporting outcomes, specifically 30-day mortality rates, for endovascular repair of CTBAD were identified. Relevant data were extracted, and a random-effects meta-analysis of proportions or means was performed to aggregate the data. Survival data were pooled using data derived from original Kaplan-Meier curves, which allows reconstruction of individual patient data. RESULTS: Forty-eight studies with 2,641 patients were identified. Early (<30 days) all-cause and aortic-related mortality rates were low at 1.6% and 0.5%, respectively. Incidence of retrograde type A dissection in the post-operative period was only 1.4%. There were also low rates of cerebrovascular accidents and spinal cord injury (1.1% and 0.9%, respectively). Late follow-up all-cause mortality was 8.0%, however, late aortic-related mortality was only 2.4%. Reintervention rates were 10.1% for endovascular and 6.7% for surgical reintervention. Pooled rates of overall survival at 1-, 3-, 5- and 10-year were 91.5%, 84.7%, 77.7% and 56.3%, respectively. CONCLUSIONS: The significant heterogeneity in the available evidence and absence of consensus reporting standards are important considerations and concern when interpreting the data. Evaluation of the evidence suggests that TEVAR for CTBAD is a safe procedure with low rates of complications. However, the optimal treatment strategy for CTBAD remains debatable and requires further research. Evidence from high-quality registries and clinical trials are required to address these challenges.

Using principal component analysis to aid bayesian network development for prediction of critical care patient outcomes.

BACKGROUND: Predicting an intensive care unit patient's outcome is highly desirable. An end goal is for computational techniques to provide updated, accurate predictions about changing patient condition using a manageable number of physiologic parameters. METHODS: Principal component analysis was used to select input parameters for critical care patient outcome models. Vital signs and laboratory values from each patient's hospital stay along with outcomes ("Discharged" vs. "Deceased") were collected retrospectively at a Level I Trauma-Military Medical Center in the southwest; intensive care unit patients were included if they had been admitted for burn, infection, or hypovolemia during a 5-year period ending October 2007. Principal component analysis was used to determine which of the 24 parameters would serve as inputs in a bayesian network developed for outcome prediction. RESULTS: Data for 581 patients were collected. Pulse pressure, heart rate, temperature, respiratory rate, sodium, and chloride were found to have statistically significant differences between Discharged and Deceased groups for "Hypovolemia" patients. For "Burn" patients, pulse pressure, hemoglobin, hematocrit, and potassium were found to have statistically significant differences. For a "Combined" group, heart rate, temperature, respiratory rate, sodium, and chloride had statistically significant differences. A bayesian network based on these results, developed for the Combined group, achieved an accuracy of 75% when predicting patient outcome. CONCLUSIONS: Outcome prediction for critical care patients is possible. Future work should explore model development using additional temporal data and should include prospective validation. Such technology could serve as the basis of real-time intelligent monitoring systems for critical patients.

Gridded daily weather data for North America with comprehensive uncertainty quantification.

Access to daily high-resolution gridded surface weather data based on direct observations and over long time periods is essential for many studies and applications including vegetation, wildlife, soil health, hydrological modelling, and as driver data in Earth system models. We present Daymet V4, a 40-year daily meteorological dataset on a 1 km grid for North America, Hawaii, and Puerto Rico, providing temperature, precipitation, shortwave radiation, vapor pressure, snow water equivalent, and day length. The dataset includes an objective quantification of uncertainty based on strict cross-validation analysis for temperature and precipitation results. The dataset represents several improvements from a previous version, and this data descriptor provides complete documentation for updated methods. Improvements include: reductions in the timing bias of input reporting weather station measurements; improvement to the three-dimensional regression model techniques in the core algorithm; and a novel approach to handling high elevation temperature measurement biases. We show cross-validation analyses with the underlying weather station data to demonstrate the technical validity of new dataset generation methods, and to quantify improved accuracy.

Fuel consumption estimation for kerbside municipal solid waste (MSW) collection activities.

Fuel consumption during seven different daily activities of a garbage co-collection truck and a normal packer truck was estimated from the trucks' global positioning system (GPS) data and fuel consumption records. The co-collection and the normal garbage packer consumed approximately 1.8 L and 1.26 L of diesel per km, respectively, while travelling within the collection areas. Using these fuel rates and the GPS data, the results show that both types of trucks consumed more than 60% of daily total fuel while actually collecting waste on the route. The average daily fuel consumption was 2-4 times higher on rural routes compared to urban areas. Fuel consumption varied significantly depending on the housing density along the collection route. In addition, approximately 5-6 times as much fuel was required to collect a kilogram of waste on a rural route compared to an urban route. Potential methods of reducing fuel consumption were examined. Consistent use of optimal collection routes could potentially save an average of 7.5 L of fuel per truck per day. Reducing the loading time per stop was also studied, but the results suggest that this method does not have significant potential to reduce fuel consumption.

Assessment of shellfish practices in licensed retail food establishments in response to increased Vibrio illnesses in a landlocked area.

Cases of non-cholera Vibrio illness are typically associated with exposure to shellfish from marine coastal areas (U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, 2009), not landlocked states such as Colorado. In 2004, a 2.8-fold increase in the incidence of non-cholera Vibrio cases in the Tri-County Health Department (TCHD) jurisdiction of Colorado prompted scrutiny of shellfish practices in local retail food establishments. Forty-three percent of establishments serving raw shellfish in the TCHD jurisdiction were in violation of one or more sections of the Colorado Retail Food Establishment Rules and Regulations (Colorado Department of Public Health and Environment, 2007a). The frequency of violations and the underutilization of safer, post-harvest processed shellfish may result in significant hazards to consumers if these practices continue.

Estimating waste transfer station delays using GPS.

This paper examines the use of on-board global positioning system (GPS) data recorders as a method to collect field data on the movements of solid waste collection vehicles at transfer stations. The movements of five waste collection vehicles using four different transfer facilities were compared over a period of 1 year. The spatial data were analyzed using geofences to determine the amount of time each truck spent on each of four activities: queuing for access to the weigh scale, sitting on the weigh scale, queuing for access to the tipping floor, and unloading waste. The study found that queuing delays can be identified and measured using GPS data. The average time at a facility for all trucks was 16.4 min per visit, with a standard deviation of 14.3 min. Time at the facility ranged between 2 and 111 min per visit and the distribution of time at the facility was positively skewed. Multi-compartment vehicles (co-collection and recycling trucks) spent significantly more time at unloading facilities. There were also significant differences in the length and the location of the queues at different facilities. At one facility, the longest delays were encountered while waiting for the weigh scale, at two facilities trucks experienced delays in obtaining access to the tipping floor, while at the fourth facility no significant delays developed.

Palatally impacted maxillary canines.

In a special article entitled, "Impacted Maxillary Canines: A Review," Samir E. Bishara states: "The ectopic eruption and impaction of maxillary permanent canines is a frequently encountered clinical problem. The diagnosis and treatment of this problem usually requires the expertise and cooperation of the general practitioner, the paediatric dentist, the oral surgeon, and the periodontist, as well as the orthodontist." We will review the etiology, diagnosis and treatment of impacted maxillary canines. A technique will be outlined that allows a competent orthodontic clinician to singly, efficiently and reliably treat this common problem without reference to a myriad of specialists.

Revisiting Health Rights Litigation and Access to Medications in Costa Rica: Preliminary Evidence from the Cochrane Collaboration Reform.

In response to the incremental creation of an expansive constitutional right to health in Costa Rica, the country's rights-friendly constitutional chamber of the Supreme Court (known as the Sala IV) unleashed a flood of litigation for medications, treatments, and other health care issues. This development was met by widespread criticism from within the health sector, which complained that the court's jurisprudence routinely elevated the right to health above financial considerations, thus posing a threat to the financial well-being of the state-run health care system.1 Further, a 2014 study by Ole Frithjof Norheim and Bruce Wilson examining successful health rights litigation revealed that more than 70% of favorable rulings were for low-priority medications, suggesting a lack of fairness in access to medications in Costa Rica.2 To address some of these criticisms, the Sala IV initiated a partnership in 2014 with the Cochrane Collaboration to incorporate medical expert evaluations into its decision-making process for claims seeking access to medications. This article examines the court's reformed decision-making process to determine whether the increased reliance on medical expertise has changed health rights jurisprudence. We reviewed all medication claims from 2016 and classified the successful cases into four groups using standard priority-setting criteria. We then compared these results with rulings issued in 2008, prior to the court's reform (and the year analyzed in Norheim and Wilson's study). Our analysis reveals that under the court's new rules, the probability of winning a medication lawsuit has increased significantly; moreover, the percentage of rulings granting experimental medications has declined while the percentage granting high-priority medications has increased. Based on these results, in comparison to the court's pre-reform jurisprudence, we can tentatively conclude that the new process has led to some minor gains in fairness.

Fuel consumption, emissions estimation, and emissions cost estimates using global positioning data.

The methodology laid out in this paper shows that typical operational data from vehicle fleets monitored by a global positioning system (GPS) can be used to estimate heavy-duty diesel vehicle (HDDV) emissions, thereby enabling waste managers and governing bodies to internalize the responsibility for socioenvironmental costs traditionally absorbed by external parties. Although municipal solid waste (MSW) collection vehicles are the subjects of this particular study, the methodology presented here can be applied to any fleet of vehicles monitored by GPS. This study indicates that MSW collection trucks may be considerably less fuel efficient in the field than published values for HDDV fuel efficiency suggest. The average fuel efficiency of one MSW collection truck was estimated as 0.90 +/- 0.44 km/L (2.12 +/- 1.03 mi/gal). This same truck would generate approximately 42 metric tons of CO2 equivalents/yr, which is comparable to the greenhouse gas emissions of a large sport utility vehicle driving six times the distance, in town, for a year. In terms of the impacts such emissions have, projections for the monetary cost of emissions are available but highly variable. They suggest that the external monetary costs of emissions range between 6 and 39% of the annual fuel costs for the studied MSW collection truck. The results of this study indicate a need for further research into valuation of the hidden, external costs of emissions, borne by local and global socioecological communities. The possible implications of this result include poorly advised fleet procurement decisions and underestimation of MSW collection fleet emissions.

Ageing and Learning in Australia: Arguing an Evidence Base for Informed and Equitable Policy.

BACKGROUND: Given Australia's population ageing and predicted impacts related to health, productivity, equity and enhancing quality of life outcomes for senior Australians, lifelong learning has been identified as a pathway for addressing the risks associated with an ageing population. To date Australian governments have paid little attention to addressing these needs and thus, there is an urgent need for policy development for lifelong learning as a national priority. The purpose of this article is to explore the current lifelong learning context in Australia and to propose a set of factors that are most likely to impact learning in later years. CONCLUSION: Evidence based policy that understands and incorporates learning opportunities for all citizens is required to meet emerging global challenges. Providing appropriate learning opportunities to seniors is one clear pathway for achieving diverse health, social and economic outcomes.

Lilac and honeysuckle phenology data 1956-2014.

The dataset is comprised of leafing and flowering data collected across the continental United States from 1956 to 2014 for purple common lilac (Syringa vulgaris), a cloned lilac cultivar (S. x chinensis 'Red Rothomagensis') and two cloned honeysuckle cultivars (Lonicera tatarica 'Arnold Red' and L. korolkowii 'Zabeli'). Applications of this observational dataset range from detecting regional weather patterns to understanding the impacts of global climate change on the onset of spring at the national scale. While minor changes in methods have occurred over time, and some documentation is lacking, outlier analyses identified fewer than 3% of records as unusually early or late. Lilac and honeysuckle phenology data have proven robust in both model development and climatic research.

Treatment of atrazine in nursery irrigation runoff by a constructed wetland.

To investigate the treatment capability of a surface flow wetland at a container nursery near Portland, Oregon, atrazine was introduced during simulated runoff events. Treatment efficiency was evaluated as the percent atrazine recovered (as percent of applied) in the water column at the wetland's outlet. Atrazine treatment efficiency at the outlet of the constructed wetland during a 7-d period ranged from 18-24% in 1998 (experiments 1-3) and 16-17% in 1999 (experiments 4 and 5). Changes in total flow, or frequency and intensity of runoff events did not affect treatment. For experiment 6 in 1999, where the amount, frequency, and duration of runoff events exceeded all other experiments, treatment was compromised. For all experiments, deethylatrazine (DEA) and deisopropylatrazine (DIA) accounted for 13-21% of the initial application. Hydroxyatrazine (HA) was rarely detected in the water. Organic carbon adsorption coefficients (Koc) were determined from batch equilibrium sorption isotherms with wetland sediment, and they decreased in the order of HA > DIA > atrazine > DEA. Static water-sediment column experiments indicated that sorption is an important mechanism for atrazine loss from water passing through the constructed wetland. The results of the MPN assay indicated the existence in the wetland of a low-density population of microorganisms with the potential to mineralize atrazine's ethyl side chain.

Health rights litigation and access to medicines: priority classification of successful cases from Costa Rica's constitutional chamber of the Supreme Court.

Although Costa Rica has no explicit constitutional right to health, its constitutional chamber of the Supreme Court (Sala IV) has become increasingly central to the resolution of many health care decisions. Some argue that courts' decisions about individuals' access to very expensive medications could upset the country's medical priorities and harm the state's general health care provision capacity. This article assesses whether health rights litigation concerning the right to medications leads to more fairness in access to medications in Costa Rica. We review randomly selected access to medicines cases successfully claimed at the Sala IV in 2008 and classify them into four priority groups using standard priority-setting criteria. We find that 2.7% of the successful cases fall into priority group I (highest priority), 27% in group II, 48.6% in group III, and 21.6% in group IV (experimental treatment). Our analysis reveals a majority of successful health rights litigation for medications results in court-mandated provision of new, expensive drugs, many with only marginal benefits. More than 70% of the successful cases evaluated concerned medications judged to be of low priority. Based on these cases, we cannot conclude that litigation leads to more fairness in access to medications.