With the escalating overdose epidemic, many surveillance efforts have appeared. In 2018, King County Medical Examiner's Office (KCMEO) initiated a fatal overdose surveillance project aimed at ...expediting death certification and disseminating timely information. In this project, KCMEO investigators collected items of evidence of drug use from overdose death scenes, which were tested by five in‐house methods, four using handheld devices: TruNarc Raman spectrometer, with and without the manufacture's H‐Kit, Rigaku ResQ Raman spectrometer, and MX908 mass spectrometer. The fifth in‐house method used fentanyl‐specific urine test strips. Results from in‐house testing were compared with results from Washington State Patrol (WSP) Materials Analysis Laboratory. From 2019 to 2022, there were 4244 evidence items of drugs and paraphernalia collected from 1777 deaths scenes. A total of 7526 in‐house tests were performed on collected specimens, and 2153 tests were performed by the WSP laboratory using standard analytical methods. The WSP results served as reference standards to calculate performance metrics of the in‐house methods. Sensitivities, specificities, and predictive values ranged from good to poor depending on the method, drug, and evidence type. Certain drugs were often associated with specific evidence types. Acetaminophen was frequently found in combination with fentanyl. Fentanyl test strips gave good scores for detecting fentanyl; otherwise, in‐house methods using handheld devices had poor performance scores with novel drugs and drugs diluted in mixtures. The results showed that in‐house testing of drug evidence has value for medical examiner overdose surveillance, but it is resource intensive, and success depends on collaboration with forensic laboratories.
As the overdose epidemic overwhelmed medicolegal death investigation offices and toxicology laboratories, the King County Medical Examiner's Office responded with "real-time" fatal overdose ...surveillance to expedite death certification and information dissemination through assembling a team including a dedicated medicolegal death investigator, an information coordinator, and student interns. In-house testing of blood, urine, and drug evidence from scenes was performed using equipment and supplies purchased for surveillance. Collaboration with state laboratories allowed validation. Applied forensic epidemiology accelerated data dissemination. From 2010 to 2022, the epidemic claimed 5815 lives in King County; the last 4 years accounted for 47% of those deaths. After initiating the surveillance project, in-house testing was performed on blood from 2836 decedents, urine from 2807, and 4238 drug evidence items from 1775 death scenes. Time to complete death certificates decreased from weeks to months to hours to days. Overdose-specific information was distributed weekly to a network of law enforcement and public health agencies. As the surveillance project tracked the epidemic, fentanyl and methamphetamine became dominant and were associated with other indicators of social deterioration. In 2022, fentanyl was involved in 68% of 1021 overdose deaths. Homeless deaths increased sixfold; in 2022, 67% of 311 homeless deaths were due to overdose; fentanyl was involved in 49% and methamphetamine in 44%. Homicides increased 250%; in 2021, methamphetamine was positive in 35% of 149 homicides. The results are relevant to the value of rapid surveillance, its impact on standard operations, selection of cases requiring autopsy, and collaboration with other agencies in overdose prevention.
To address the challenges in monitoring the continuously accelerating drug overdose epidemic, the King County Medical Examiner's Office in Seattle, Washington, instituted a "real-time" fatal drug ...overdose surveillance project, depending on scene investigations, autopsy findings, and in-house testing of blood, urine, and drug evidence collected from death scenes. Validation of the project's rapid death certification methodology from 2019 through 2021 was performed at the following 3 levels: blood testing, urine testing, and death certification, and for the following 4 drugs: fentanyl, opiate, methamphetamine, and cocaine. For blood testing, sensitivity ranged from 90% to 99%, and specificity ranged from 86% to 97%. For urine testing, sensitivity ranged from 91% to 92%, and specificity ranged from 87% to 97%. The positive predictive value for cocaine was poor for both blood testing (57%) and urine testing (72%). Of 1034 deaths, 807 were certified as overdose by rapid methodology, and 803 (99.5%) were confirmed by formal toxicology results. Manners of death were changed from accident to natural in 3 of 1034 cases (0.29%). Results of this study indicate that the rapid overdose surveillance methodology described in this study offers benefits to families and provides useful, timely information for responding law enforcement and public health agencies.
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman ...should look like. The message should be “eat better, not more.” This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report “prudent” or “health-conscious” eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed.
Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
Notes for the Next Century Anyon, Roger; Barbour, Matthew J.; Bernhart, Bob ...
The Kiva (Tucson, Ariz.),
11/2015, Volume:
81, Issue:
1-2
Journal Article
Amphiphilic polyhedron-shaped p-sulfonatocalix4arene building blocks, which have been previously shown to assemble into bilayers in an antiparallel fashion, have been assembled in a parallel ...alignment into spherical and helical tubular structures by the addition of pyridine N-oxide and lanthanide ions. Crystallographic studies revealed how metal ion coordination and substrate recognition direct the formation of these supramolecular assemblies. The addition of greater amounts of pyridine N-oxide changed the curvature of the assembling surface and resulted in the formation of extended tubules.
Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line ...alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two recent clinical randomized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity. These developmental programming effects challenge the conclusion that metformin is equivalent to insulin. Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used, there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide. Moreover, it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and high rates of maternal hypoglycemia. We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists, which recommend insulin as the preferred agent, but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide, we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target medications based on individual patterns of hyperglycemia, and follow the offspring long-term for metabolic risk.
Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional ...low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher-complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity.
At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks.
After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE (10.1 ± 1.4 vs. 12.6 ± 2%, respectively).
A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet.
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