Assessment of the Roles of Magnesium and Zinc in Clinical Disorders.

The ability and facility of magnesium (Mg2+) and zinc (Zn2+) to interact with phosphate ions confer them the characteristics of essential trace elements. Trace elements are extremely necessary for the basic nucleic acid chemistry of cells of all known living organisms. More than 300 enzymes require zinc and magnesium ions for their catalytic actions, including all the enzymes involved in the synthesis of ATP. In addition, enzymes such as isomerases, oxidoreductases, lyases, transferases, ligases and hydrolases that use other nucleotides to synthesize DNA and RNA require magnesium and zinc. These nucleotides may trigger oxidative damage or important changes against free radicals. In the same way, nucleotides may play an important role in the pathophysiology of degenerative diseases, including in some clinical disorders, where vascular risk factors, oxidative stress and inflammation work to destabilize the patients` homeostatic equilibrium. Indeed, reduced levels of zinc and magnesium may lead to inadequate amount of antioxidant enzymes, and thus, acts as an important contributing factor for the induction of oxidative stress leading to cellular or tissue dysfunction. Hence, the development of zinc or magnesium enzyme inhibitors could be a novel opportunity for the treatment of some human disorders. Therefore, the objective of the present work was to assess the clinical benefits of zinc and magnesium in human health and their effects in some clinical disorders.

Ultrasound assessment of muscle mass and correlation with clinical outcomes in critically ill patients: a prospective observational study.

PURPOSE: Muscular atrophy implies structural and functional alterations related to muscular force production and movement. This condition has been reported to be the main reason for generalized muscle weakness; it reflects the severity of the disease and can have a profound impact on short- and long-term clinical outcomes. The purpose of this study was to determine whether muscle atrophy ultrasound parameters early predict muscle weakness, morbidity, or 28-days mortality. METHODS: This was a prospective, observational single center cohort study. Ultrasound was used to determine the cross-sectional area and muscle thickness of the rectus femoris on the first and third day of ICU stay. The main outcome was the incidence of significant muscle atrophy (≥ 10%). RESULTS: Ultrasound measurements were made in 31 patients, 58% (18/31) of which showed significant muscle atrophy. The relative loss of muscle mass per day was 1.78 at 5% per day. The presence of muscle atrophy presents increased risk for limb muscle weakness and handgrip weakness. The 28-days mortality rate was similar in both subgroups. CONCLUSION: The presence of muscle atrophy presents an increased clinical risk for the development of limb ICUAW and handgrip, although these observations were not statistically significant. The results could be used to plan future studies on this topic.

Pain Recognition and Assessment in Birds.

The recognition and assessment of pain in avian species are crucial tools in providing adequate supportive care in clinical, laboratory, zoologic, rehabilitation, and companion animal settings. With birds being a highly diverse class of species, there is still much to be determined regarding how to create specific criteria to recognize and assess pain in these animals. This article provides a clinical review on the physiology of pain in birds, observed behavioral and physiologic alterations with pain, how different sources and degrees of pain can alter behaviors observed, and how this information can be applied in a clinical setting.

Recognition and Assessment of Pain-Related Behaviors in Avian Species: An Integrative Review.

The appropriate recognition and assessment of pain in animals is an essential tool that can be used by veterinary professionals, rehabilitators, household caregivers, and others to provide supportive care and analgesia to patients. Although the use of behavioral, postural, and facial changes to recognize pain have been studied in popular domestic species such as dogs (Canis lupus familiaris), cats (Felis catus), and rabbits (Oryctolagus cuniculus), very little is known relative to avian species. The purpose of this article is to provide a literature review comprising structured searches on the topic of avian pain recognition. The emphasis of the searches were based on the behavioral and postural alterations that have thus far been explored. The literature review was performed in the months of August-September 2020 over 5 online databases: MEDLINE/ PubMed, CAB Direct, Biosis, Zoological Record, and Scopus. Additional "snowballing" was incorporated by looking at the references and articles that cited the 126 articles from the initial abstract and full-text screening. Of the 194 full-text articles reviewed, 132 sources of literature were included in the final analysis. From these 132 sources of literature, 31.8% were general review articles in which avian pain behaviors were described irrespective of species, with others being specific to a particular species (chickens 47.8%, turkeys 7.6%, parrots 3.8%, pigeons [Columba livia] 3%, raptors 3%, and "other" 3%-2 on ducks, 1 on emus [Dromaius novaehollandiae], and 1 on Eurasian blue tits [Cyanistes caeruleus]). Pain stimulus varied depending on species, although the vast majority of the pain stimuli involved welfare issues such as beak trimming, limb abnormalities, and keel bone fractures in chickens. Although information regarding this topic remains limited for many avian species, this review provides a more thorough understanding of behavioral indicators of pain in species such as chickens, turkeys, psittacines, pigeons, raptors, and select others. It is the hope that this review will motivate further interest and future analgesia research for the improvement of avian welfare.

Association of Low Socioeconomic Status With Premature Coronary Heart Disease in US Adults.

Importance: Individuals with low socioeconomic status (SES) bear a disproportionate share of the coronary heart disease (CHD) burden, and CHD remains the leading cause of mortality in low-income US counties. Objective: To estimate the excess CHD burden among individuals in the United States with low SES and the proportions attributable to traditional risk factors and to other factors associated with low SES. Design, Setting, and Participants: This computer simulation study used the Cardiovascular Disease Policy Model, a model of CHD and stroke incidence, prevalence, and mortality among adults in the United States, to project the excess burden of early CHD. The proportion of this excess burden attributable to traditional CHD risk factors (smoking, high blood pressure, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, type 2 diabetes, and high body mass index) compared with the proportion attributable to other risk factors associated with low SES was estimated. Model inputs were derived from nationally representative US data and cohort studies of incident CHD. All US adults aged 35 to 64 years, stratified by SES, were included in the simulations. Exposures: Low SES was defined as income below 150% of the federal poverty level or educational level less than a high school diploma. Main Outcomes and Measures: Premature (before age 65 years) myocardial infarction (MI) rates and CHD deaths. Results: Approximately 31.2 million US adults aged 35 to 64 years had low SES, of whom approximately 16 million (51.3%) were women. Compared with individuals with higher SES, both men and women in the low-SES group had double the rate of MIs (men: 34.8 [95% uncertainty interval (UI), 31.0-38.8] vs 17.6 [95% UI, 16.0-18.6]; women: 15.1 [95% UI, 13.4-16.9] vs 6.8 [95% UI, 6.3-7.4]) and CHD deaths (men: 14.3 [95% UI, 13.0-15.7] vs 7.6 [95% UI, 7.3-7.9]; women: 5.6 [95% UI, 5.0-6.2] vs 2.5 [95% UI, 2.3-2.6]) per 10 000 person-years. A higher burden of traditional CHD risk factors in adults with low SES explained 40% of these excess events; the remaining 60% of these events were attributable to other factors associated with low SES. Among a simulated cohort of 1.3 million adults with low SES who were 35 years old in 2015, the model projected that 250 000 individuals (19%) will develop CHD by age 65 years, with 119 000 (48%) of these CHD cases occurring in excess of those expected for individuals with higher SES. Conclusions and Relevance: This study suggested that, for approximately one-quarter of US adults aged 35 to 64 years, low SES was substantially associated with early CHD burden. Although biomedical interventions to modify traditional risk factors may decrease the disease burden, disparities by SES may remain without addressing SES itself.

Risk Factors for Falls in Older Adults Experiencing Homelessness: Results from the HOPE HOME Cohort Study.

BACKGROUND: More than half of homeless adults are of age ≥ 50 years. Falls are a common cause of morbidity in older adults in the general population. Risk factors for falls in the general population include poor health, alcohol use, and exposure to unsafe environments. Homeless adults aged ≥ 50 have a high prevalence of known risk factors and face additional potential risks. OBJECTIVES: To examine the prevalence of and risk of falling in a cohort of older homeless adults. DESIGN: Longitudinal cohort study with participant interviews every 6 months for 3 years; data were analyzed using generalized estimating equations (GEEs). PARTICIPANTS: Three hundred fifty adults aged ≥ 50, homeless at study entry, recruited via population-based sampling. MEASURES: The dependent variable is any falls in prior 6 months; independent variables include individual (i.e., illness, behaviors) and social/environmental (i.e., social support, experiencing violence, living unsheltered) factors. RESULTS: Over three quarters of participants were men (77.1%) and Black (79.7%). The median age was 58 (IQR 54, 61). At baseline, one third (33.7%) reported a fall in the prior 6 months. At follow-up visits, 23.1% to 31.2% of participants reported having fallen. In GEE models, individual risk factors (non-Black race, being a women, older age, functional impairment, urinary incontinence, history of stroke, and use of assistive devices, opioid, and marijuana) were associated with increased odds of falls. Environmental and social factors (spending any nights unsheltered (adjusted odds ratio (AOR) = 1.42, CI = 1.10-1.83) and experiencing physical assault (AOR = 1.67, CI = 1.18-2.37) were also associated. CONCLUSIONS: Older homeless adults fall frequently. Likely contributors include having a high prevalence of conditions that increase the risk of falls, compounded by heightened exposure to unsafe environments. Fall prevention in this population should target those at highest risk and address modifiable environmental conditions. Providing shelter or housing and addressing substance use could reduce morbidity from falls in homeless older adults.

The Harm of Ableism: Medical Error and Epistemic Injustice.

This paper argues that epistemic errors rooted in group- or identity-based biases, especially those pertaining to disability, are undertheorized in the literature on medical error. After sketching dominant taxonomies of medical error, we turn to the field of social epistemology to understand the role that epistemic schemas play in contributing to medical errors that disproportionately affect patients from marginalized social groups. We examine the effects of this unequal distribution through a detailed case study of ableism. There are four primary mechanisms through which the epistemic schema of ableism distorts communication between nondisabled physicians and disabled patients: testimonial injustice, epistemic overconfidence, epistemic erasure, and epistemic derailing. Measures against epistemic injustices in general and against schema-based medical errors in particular are ultimately issues of justice that must be better addressed at all levels of health care practice.

Unmet mental health and substance use treatment needs among older homeless adults: Results from the HOPE HOME Study.

AIMS: To examine the prevalence of and factors associated with unmet need for mental health and substance use treatment in older homeless adults. METHODS: Among 350 homeless adults aged ≥50, we examined prevalence of mental health and substance use problems and treatment. Using logistic regression, we examined factors associated with unmet treatment need. RESULTS: Among those with a mental health problem, being aged ≥65 was associated with an increased odds, while having a regular healthcare provider and case manager were associated with a decreased odds of having unmet need for mental health treatment. A first homelessness episode at age ≥50 was associated with increased, while spending time in jail/prison or having a case manager was associated with decreased odds of unmet needs for substance use treatment. CONCLUSION: Older homeless adults have a high prevalence of unmet behavioral health treatment need. There is a need for targeted services for this population.

Albuminuria Testing by Race and Ethnicity among Patients with Hypertension with and without Diabetes.

BACKGROUND: Detection of chronic kidney disease (CKD) with urine albumin-to-creatinine ratio (UACR) among patients with hypertension (HTN) provides an opportunity for early treatment, potentially mitigating risk of CKD progression and cardiovascular complications. Differences in UACR testing patterns among racial/ethnic populations at risk for CKD could contribute to known disparities in CKD complications. METHODS: We examined the prevalence of UACR testing among low-income adult primary care patients with HTN, defined by a new administrative code for HTN or 2 clinic blood pressures >140/90 mm Hg between January 1, 2014, and January 1, 2017, in one public health-care delivery system with a high prevalence of end-stage kidney disease among race/ethnic minorities. Logistic regression was used to identify odds of UACR testing within 1 year of a HTN diagnosis, overall, and by racial/ethnic subgroup, adjusted for demographic factors, estimated glomerular filtration rate, and HTN severity. Models were also stratified by diabetes status. RESULTS: The cohort (n = 16,414) was racially/ethnically diverse (16% White, 21% Black, 34% Asian, 19% Hispanic, and 10% other) and 51% female. Only 35% of patients had UACR testing within 1 year of a HTN diagnosis. Among individuals without diabetes, odds of UACR testing were higher among Asians, Blacks, and Other subgroups compared to Whites (adjusted OR [aOR] 1.19; 95% CI 1.00-1.42 for Blacks; aOR 1.33; 1.13-1.56 for Asians; aOR 1.30; 1.04-1.60 for Other) but were not significantly different between Hispanics and Whites (aOR 1.17; 0.97-1.39). Among individuals with diabetes, only Asians had higher odds of UACR testing compared to Whites (aOR 1.35; 1.12-1.63). CONCLUSIONS: Prevalence of UACR testing among low-income patients with HTN is low in one public health-care delivery system, with higher odds of UACR testing among racial/ethnic minority subgroups compared to Whites without diabetes and similar odds among those with diabetes. If generalizable, less albuminuria testing may not explain higher prevalence of kidney failure in racial/ethnic minorities.

High perceived social support and hospital readmissions in an older multi-ethnic, limited English proficiency, safety-net population.

BACKGROUND: Early readmission amongst older safety-net hospitalized adults is costly. Interventions to prevent early readmission have had mixed success. The role of perceived social support is unclear. We examined the association of perceived social support in 30-day readmission or death in older adults admitted to a safety-net hospital. METHODS: This is an observational cohort study derived from the Support From Hospital to Home for Elders (SHHE) trial. Participants were community-dwelling English, Spanish and Chinese speaking older adults admitted to medicine wards at an urban safety-net hospital in San Francisco. We assessed perceived social support using the Multidimensional Scale of Perceived Social Support (MSPSS). We defined high social support as the highest quartile of MSPSS. We ascertained 30-day readmission and mortality based on a combination of participant self-report, hospital and death records. We used multiple/multivariable logistic regression to adjust for patient demographics, health status, and health behaviors. We tested for whether race/ethnicity modified the effect high social support had on 30-day readmission or death by including a race-social support interaction term. RESULTS: Participants (n = 674) had mean age of 66.2 (SD 9.0), with 18.8% White, 24.8% Black, 31.9% Asian, and 19.3% Latino. The 30-day readmission or death rate was 15.0%. Those with high social support had half the odds of readmission or death than those with low social support (OR = 0.47, 95% CI 0.26-0.88). Interaction analyses revealed race modified this association; higher social support was protective against readmission or death among minorities (AOR = 0.35, 95% CI 0.16-0.76) but increased likelihood of readmission or death among Whites (AOR = 3.7, 95% CI 1.07-12.9). CONCLUSION: In older safety-net patients nearing discharge, high perceived social support may protect against 30-day readmission or death among minorities. Assessing patients' social support may aid targeting of transitional care resources and intervention design. How perceived social support functions across racial/ethnic groups in health outcomes warrants further study. TRIAL REGISTRATION: NIH trials registry number ClinicalTrials.gov: NCT01221532 .

The Use of Trace and Essential Elements in Common Clinical Disorders: Roles in Assessment of Health and Oxidative Stress Status.

During the early life, the diet of infants is mainly dominated by milk. Milk is a natural food rich in trace elements focus on essential elements. These elements are very necessary for human metabolism and since they cannot be synthesized by the body, the only source available for the humans to obtain them is by ingestion of natural food. This mini-review aims at updating the knowledge on trace elements, outlining their natural food sources, and their possible implications in common clinical disorders in early and adult life. However, it was found that consumption of food with micronutrients and trace elements may release intracellular compounds and offer oxidative protection or exacerbate oxidative damage to metabolically compromised cells.

Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial.

Background: The ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial included participants with a recent acute coronary syndrome. Compared with participants receiving statins alone, those receiving a statin plus alirocumab had lower rates of a composite outcome including myocardial infarction (MI), stroke, and death. Objective: To determine the cost-effectiveness of alirocumab in these circumstances. Design: Decision analysis using the Cardiovascular Disease Policy Model. Data Sources: Data sources representative of the United States combined with data from the ODYSSEY Outcomes trial. Target Population: U.S. adults with a recent first MI and a baseline low-density lipoprotein cholesterol level of 1.81 mmol/L (70 mg/dL) or greater. Time Horizon: Lifetime. Perspective: U.S. health system. Intervention: Alirocumab or ezetimibe added to statin therapy. Outcome Measures: Incremental cost-effectiveness ratio in 2018 U.S. dollars per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Compared with a statin alone, the addition of ezetimibe cost $81 000 (95% uncertainty interval [UI], $51 000 to $215 000) per QALY. Compared with a statin alone, the addition of alirocumab cost $308 000 (UI, $197 000 to $678 000) per QALY. Compared with the combination of statin and ezetimibe, replacing ezetimibe with alirocumab cost $997 000 (UI, $254 000 to dominated) per QALY. Results of Sensitivity Analysis: The price of alirocumab would have to decrease from its original cost of $14 560 to $1974 annually to be cost-effective relative to ezetimibe. Limitation: Effectiveness estimates were based on a single randomized trial with a median follow-up of 2.8 years and should not be extrapolated to patients with stable coronary heart disease. Conclusion: The price of alirocumab would have to be reduced considerably to be cost-effective. Because substantial reductions already have occurred, we believe that timely, independent cost-effectiveness analyses can inform clinical and policy discussions of new drugs as they enter the market. Primary Funding Source: University of California, San Francisco, and Institute for Clinical and Economic Review.

Adapting and Evaluating a Health System Intervention From Kaiser Permanente to Improve Hypertension Management and Control in a Large Network of Safety-Net Clinics.

BACKGROUND: Nearly half of Americans with diagnosed hypertension have uncontrolled blood pressure (BP) while some integrated healthcare systems, such as Kaiser Permanente Northern California, have achieved control rates upwards 90%. METHODS AND RESULTS: We adapted Kaiser Permanente's evidence-based treatment protocols in a racially and ethnically diverse population at 12 safety-net clinics in the San Francisco Health Network. The intervention consisted of 4 elements: a hypertension registry, a simplified treatment intensification protocol that included fixed-dose combination medications containing diuretics, standardized BP measurement protocol, and BP check visits led by registered nurse and pharmacist staff. The study population comprised patients with hypertension who made ≥1 primary care visits within the past 24 months (n=15 917) and had a recorded BP measurement within the past 12 months. We conducted a postintervention time series analysis from August 2014 to August 2016 to assess the effect of the intervention on BP control for 24 months for the pilot site and for 15 months for 11 other San Francisco Health Network clinics combined. Secondary outcomes were changes in use of guideline-recommended medication prescribing. Rates of BP control increased at the pilot site (68%-74%; P<0.01) and the 11 other San Francisco Health Network clinic sites (69%-74%; P<0.01). Statistically significant improvements in BP control rates (P<0.01) at the 11 San Francisco Health Network clinic sites occurred in all racial and ethnic groups (blacks, 60%-66%; whites, 69%-75%; Latinos, 67%-72%; Asians, 78%-82%). Use of fixed-dose combination medications increased from 10% to 13% (P<0.01), and the percentage of angiotensin-converting enzyme inhibitor prescriptions dispensed in combination with a thiazide diuretic increased from 36% to 40% (P<0.01). CONCLUSIONS: Evidence-based system approaches to improving BP control can be implemented in safety-net settings and could play a pivotal role in achieving improved population BP control and reducing hypertension disparities.

Advance Care Planning for Older Homeless-Experienced Adults: Results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age Study.

Older homeless-experienced adults have low engagement in advance care planning (ACP) despite high morbidity and mortality. We conducted a cross-sectional analysis of a cohort of 350 homeless-experienced adults aged 50 and older in Oakland, California. We assessed the prevalence of potential surrogate decision-makers, ACP contemplation, discussions, and ACP documentation (surrogate designation, advance directives). We used multivariable logistic regression to examine factors associated with ACP discussions and documentation. The median age of the cohort was 59 (range 52-82), 75.2% were male, and 82.1% were black. Sixty-one percent reported a potential surrogate, 21.5% had discussed ACP, and 19.0% reported ACP documentation. In multivariable models, having 1 to 5 confidants versus none (adjusted odds ratio (aOR)=5.8, 95% confidence interval (CI)=1.7-20.0), 3 or more chronic conditions versus none (aOR=2.3, 95% CI=0.9-5.6), and a recent primary care visit (aOR=2.1, 95% CI=1.0-4.4) were associated with higher odds of ACP discussions and each additional 5 years of homelessness (aOR=0.7, 95% CI=0.5-0.9) with lower odds. Having 1 to 5 confidants (aOR=5.0, 95% CI=1.4-17.5), being black (aOR=5.5, 95% CI=1.5-19.5), and having adequate versus limited literacy (aOR=7.0, 95% CI=1.5-32.4) were associated with higher odds of ACP documentation and illicit drug use (aOR=0.3, 95% CI=0.1-0.9) with lower odds. Although the majority of older homeless-experienced adults have a potential surrogate, few have discussed or documented their ACP wishes; the odds of both were greater with larger social networks. Future interventions must be customized for individuals with limited social networks and address the instability of homelessness, health literacy, and the constraints of safety-net healthcare settings.

Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats.

BACKGROUND: The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. OBJECTIVE: The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. METHODS: Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium (S.Typh) (1 × 106 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H2O2, and total ATPase activity using validated methods. RESULTS: DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh. 5-HIAA, GSH, and H2O2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh. TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. CONCLUSION: MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. SUMMARY: The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar.

Management of Hypertension in Primary Care Safety-Net Clinics in the United States: A Comparison of Community Health Centers and Private Physicians' Offices.

OBJECTIVE: To examine adherence to guideline-concordant hypertension treatment practices at community health centers (CHCs) compared with private physicians' offices. DATA SOURCES/STUDY SETTING: National Ambulatory Medical Care Survey from 2006 to 2010. STUDY DESIGN: We examined four guideline-concordant treatment practices: initiation of a new medication for uncontrolled hypertension, use of fixed-dose combination drugs for patients on multiple antihypertensive medications, use of thiazide diuretics among patients with uncontrolled hypertension on ≥3 antihypertensive medications, and use of aldosterone antagonist for resistant hypertension, comparing use at CHC with private physicians' offices overall and by payer group. DATA COLLECTION/EXTRACTION METHODS: We identified visits of nonpregnant adults with hypertension at CHCs and private physicians' offices. PRINCIPAL FINDINGS: Medicaid patients at CHCs were as likely as privately insured individuals to receive a new medication for uncontrolled hypertension (AOR 1.0, 95 percent CI: 0.6-1.9), whereas Medicaid patients at private physicians' offices were less likely to receive a new medication (AOR 0.3, 95 percent CI: 0.1-0.6). Use of fixed-dose combination drugs was lower at CHCs (AOR 0.6, 95 percent CI: 0.4-0.9). Thiazide use for patients was similar in both settings (AOR 0.8, 95 percent CI: 0.4-1.7). Use of aldosterone antagonists was too rare (2.1 percent at CHCs and 1.5 percent at private clinics) to allow for statistically reliable comparisons. CONCLUSIONS: Increasing physician use of fixed-dose combination drugs may be particularly helpful in improving hypertension control at CHCs where there are higher rates of uncontrolled hypertension.

Out-of-Network Emergency Department Use among Managed Medicaid Beneficiaries.

OBJECTIVE: Out-of-network emergency department (ED) use, or use that occurs outside the contracted network, may lead to increased care fragmentation and cost. We examined factors associated with out-of-network ED use among Medicaid beneficiaries. DATA SOURCES AND STUDY SETTING: Enrollment, claims, and encounter data for adult Medi-Cal health plan members with 1+ ED visits and complete Medicaid eligibility during the study period from 2013 to 2014. STUDY DESIGN: We analyzed the data to identify factors associated with out-of-network ED use classified by mode of arrival (ambulance vs. nonambulance). DATA EXTRACTION METHODS: We extracted encounter, ambulance, and ED census data and linked them together based on ED visit date. PRINCIPAL FINDINGS: Of 11,143 ED visits, 6,808 (61.1 percent) were out-of-network. The number of hours the study ED was on ambulance diversion increased the odds of out-of-network visits for the 3,365 (30.2 percent) ED visits arriving by ambulance. For all visit types, assignment to a primary care clinic at the in-network hospital and having had any primary care visit during the study period decreased the odds of out-of-network ED care. Individuals were more likely to go out-of-network for ED care if they lived in neighborhoods containing out-of-network EDs. CONCLUSIONS: There are a number of factors related to out-of-network ED use, including the proximity and density of out-of-network EDs, race and ethnicity, a prior history of out-of-network ED use, and individuals' connection to primary care. EDs that serve Medicaid beneficiaries may need to explore alternative sites and modalities of care as alternatives to the ED, and consider their ability to absorb large numbers of out-of-network visits given already limited capacity.

Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease.

IMPORTANCE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD) and have potential for broad ASCVD prevention. Their long-term cost-effectiveness and effect on total health care spending are uncertain. OBJECTIVE: To estimate the cost-effectiveness of PCSK9 inhibitors and their potential effect on US health care spending. DESIGN, SETTING, AND PARTICIPANTS: The Cardiovascular Disease Policy Model, a simulation model of US adults aged 35 to 94 years, was used to evaluate cost-effectiveness of PCSK9 inhibitors or ezetimibe in heterozygous FH or ASCVD. The model incorporated 2015 annual PCSK9 inhibitor costs of $14,350 (based on mean wholesale acquisition costs of evolocumab and alirocumab); adopted a health-system perspective, lifetime horizon; and included probabilistic sensitivity analyses to explore uncertainty. EXPOSURES: Statin therapy compared with addition of ezetimibe or PCSK9 inhibitors. MAIN OUTCOMES AND MEASURES: Lifetime major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke), incremental cost per quality-adjusted life-year (QALY), and total effect on US health care spending over 5 years. RESULTS: Adding PCSK9 inhibitors to statins in heterozygous FH was estimated to prevent 316,300 MACE at a cost of $503,000 per QALY gained compared with adding ezetimibe to statins (80% uncertainty interval [UI], $493,000-$1,737,000). In ASCVD, adding PCSK9 inhibitors to statins was estimated to prevent 4.3 million MACE compared with adding ezetimibe at $414,000 per QALY (80% UI, $277,000-$1,539,000). Reducing annual drug costs to $4536 per patient or less would be needed for PCSK9 inhibitors to be cost-effective at less than $100,000 per QALY. At 2015 prices, PCSK9 inhibitor use in all eligible patients was estimated to reduce cardiovascular care costs by $29 billion over 5 years, but drug costs increased by an estimated $592 billion (a 38% increase over 2015 prescription drug expenditures). In contrast, initiating statins in these high-risk populations in all statin-tolerant individuals who are not currently using statins was estimated to save $12 billion. CONCLUSIONS AND RELEVANCE: Assuming 2015 prices, PCSK9 inhibitor use in patients with heterozygous FH or ASCVD did not meet generally acceptable incremental cost-effectiveness thresholds and was estimated to increase US health care costs substantially. Reducing annual drug prices from more than $14,000 to $4536 would be necessary to meet a $100,000 per QALY threshold.

Assessment of the effects of oseltamivir and indomethacin on dopamine, 5-HIAA, and some oxidative stress markers in stomach and brain of Salmonella typhimurium-infected rats.

OBJECTIVES: The purpose of this study was to measure the effect of oseltamivir and indomethacin on dopamine and 5-HIAA levels and some oxidative biomarkers in brain and stomach of young rats in conditions of infection. METHODS: Female Sprague Dawley rats in absence or presence of a live culture of Salmonella typhimurium (S.Typh), were treated as follows: PBS, group 1 (control); oseltamivir (100 mg/kg), group 2; indomethacin (67 µg/kg) group 3; oseltamivir (100 mg/kg) + indomethacin (67 µg/kg), group 4. The drugs were administered intraperitoneally every 24 hr for 5 days while S. Typh was give orally in the first and third day. C-reactive proteins was measured in blood on sacrifice, and from brain extract, dopamine and 5-HIAA levels as well as GSH, calcium, and H2O2 and total ATPase activity were measured by validated methods. RESULTS: Dopamine increased significantly in cortex and cerebellum/medulla oblongata of groups that received indomethacin and oseltamivir. 5-HIAA increased significantly in all groups that received S.Typh. H2O2 decreased significantly in cortex regions of animals that received oseltamivir and indomethacin in presence of S.Typh. Total ATPase increased significantly in cortex and hemispheres of groups that received oseltamivir as well as in cerebellum/medulla oblongata and stomach of animals that received oseltamivir and indomethacin combined with S.Typh. GSH increased and calcium decreased significantly in stomach of animals that received oseltamivir or indomethacin alone or combined with S.Typh. CONCLUSION: These results demonstrate the association between inflammatory response, oxidative stress, dopaminergic, and serotonergic metabolism in an experimental inflammatory animal model.

Displaying radiation exposure and cost information at order entry for outpatient diagnostic imaging: a strategy to inform clinician ordering.

BACKGROUND: Displaying radiation exposure and cost information at electronic order entry may encourage clinicians to consider the value of diagnostic imaging. METHODS: An urban safety-net health system displayed radiation exposure information for CT and cost information for CT, MRI and ultrasound on an electronic referral system for outpatient ordering. We assessed whether there were differences in numbers of outpatient CT scans and MRIs per month relative to ultrasounds before and after the intervention, and evaluated primary care clinicians' responses to the intervention. RESULTS: There were 23 171 outpatient CTs, 15 052 MRIs and 43 266 ultrasounds from 2011 to 2014. The ratio of CTs to ultrasounds decreased by 15% (95% CI 9% to 21%), from 58.2 to 49.6 CTs per 100 ultrasounds; the ratio of MRIs to ultrasounds declined by 13% (95% CI 7% to 19%), from 37.5 to 32.5 per 100. Of 300 invited, 190 (63%) completed the web-based survey in 17 clinics. 154 (81%) noticed the radiation exposure information and 158 (83.2%) noticed the cost information. Clinicians believed radiation exposure information was more influential than cost information: when unsure clinically about ordering a test (radiation=69.7%; cost=46.4%), when a patient wanted a test not clinically indicated (radiation=77.5%; cost=54.8%), when they had a choice between imaging modalities (radiation=77.9%; cost=66.6%), in patient care discussions (radiation=71.9%; cost=43.2%) and in trainee discussions (radiation=56.5%; cost=53.7%). Resident physicians and nurse practitioners were more likely to report that the cost information influenced them (p<0.05). CONCLUSIONS: Displaying radiation exposure and cost information at order entry may improve clinician awareness about diagnostic imaging safety risks and costs. More clinicians reported the radiation information influenced their clinical practice.