Pharmacotherapy for gastric and intestinal cramping pain: current and emerging therapies.

INTRODUCTION: Acute gastrointestinal cramping pain (GICP) is a debilitating condition that affects many people worldwide, significantly reducing their quality of life. As such, prompt treatment is crucial. AREAS COVERED: This article will explore relevant literature from databases such as PubMed, Scopus, Google Scholar, Cochrane Library, and Web of Science. Additionally, we searched ClinicalTrials.gov and the WHO ICTRP database for the latest clinical trials. EXPERT OPINION: Consensus dictates that antispasmodics such as hyoscine-N-butyl bromide and mebeverine should be the primary treatment for GICP. If these prove ineffective, patients can switch to an antispasmodic with a different mode of action or add acetaminophen/NSAIDs for more severe cases. Currently, several antispasmodics are undergoing clinical trials, including drotaverine, alverine, pinaverium, otilonium bromide, fenoverine, tiropramide, otilonium bromide, trimebutine, and peppermint oil. Well-designed head-to-head studies are necessary to evaluate current antispasmodics' safety, efficacy, pharmacokinetic, and pharmacoeconomics profiles. Recent studies have shown that fixed-dose combinations of antispasmodics + NSAIDs or two different antispasmodics can improve patient compliance and synergistically reduce GICP. Therefore, it is recommended that the global availability and accessibility of these products be enhanced.

Assessment of cloth masks ability to limit Covid-19 particles spread: a systematic review.

After the spread of Covid 19 worldwide, the use of cloth masks increased significantly due to a shortage of medical masks. Meanwhile, there were different opinions about the effectiveness of these masks and, so far, no study has been done to find the best fabric masks. This study reviews and summarizes all studies related to fabric masks' effectiveness and various fabrics against coronavirus. This systematic review is based on PRISMA rules. Two researchers separately examined three databases: PubMed, Scopus, and Web of Science. Laboratory and clinical studies were included. After extracting the articles, their quality was assessed with the Joanna Briggs Institute (JBI) tool. In addition to efficacy, other factors, including the penetration of masks, pressure drop, and quality factor, were examined to select the best fabrics. Of the 42 studies selected, 39 were laboratory studies, and 3 were clinical studies. Among the various fabrics examined, cotton quilt 120 thread per inch (TPI), copy paper (bonded), hybrid of cotton with chiffon/ silk, and flannel filtration were found to have over 90% effectiveness in the particle size range of Covid-19. The results and comparison of different factors (pressure drop, filtration efficacy, penetration, filtration quality, and fit factor have been evaluated) showed that among different fabrics, hybrid masks, 2-layered cotton quilt, 2-layered 100% cotton, cotton flannel, and hairy tea towel + fleece sweater had the best performance. Clinical studies have not explicitly examined cloth masks' effectiveness in Covid-19, so the effectiveness of these types of masks for Covid 19 is questionable, and more studies are needed.

The Effect of Levosimendan on Phosphine-Induced Nephrotoxicity: Biochemical and Histopathological Assessment.

BACKGROUND: Aluminum phosphide (AlP) toxicity is associated with a high risk of death due to heart, liver, and kidney failure as the target organs. Phosphine gas released due to the ingestion is the main factor involved in the multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs. This study aimed to investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat model. METHOD: Six groups included control group (almond oil only), sole LEV group (48 µg/kg), AlP group (LD50=10 µg/kg), and the poisoned groups treated with LEV at doses of 12, 24, and 48 µg/kg 30 min after AlP gavage. After 24 hours of treatment, serum and kidney samples were taken for biochemical and histopathological analyses. RESULT: Biochemical analysis of the AlP group showed that the activity of complexes I, II, and IV was significantly reduced, while the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS), lactate, and myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live renal cells and elevated necrosis. However, the levels of serum creatinine and blood urea nitrogen were not affected by the poisoning. LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels. Additionally, the histopathological analysis showed the detrimental effects of AlP on kidney tissue, which was mitigated by LEV administration. CONCLUSION: Our findings showed that LEV can potentially improve oxidative stress, imbalance in the redox status, necrosis, and pathological injuries in kidney tissue following AlP-poisoning.

Comprehensive study on the administrative, economic, regional, and regulatory prospects of complementary and alternative medicine (CAM) in inflammatory bowel disease (IBD).

Introduction: Due to the high cost, low effectiveness, and adverse effects plus the life-long nature of inflammatory bowel disease (IBD), and misconception on safety, efficacy, and cost-effectiveness of complementary and alternative medicine (CAM), the market demand for CAM has risen over the past decades. A critical review of patients' and physicians' attitudes, market drivers, economic aspects, regulatory roles, and regional distribution is lacking.Areas covered: Through relevant databases, the existing English language literature concerning the association of CAM use with IBD was collected over the past two decades. Data was then analyzed, comprehensively summarized in tables/figures, and justified concerning administrative, organizational, regional, economic, and regulatory perspectives.Expert opinion: Although CAM utilization is more prevalent among younger, female, and high-educated IBD patients, issues concerning weak study designs, limited-time period/regional distribution of recent surveys, and lack of economic evaluations on CAM make it entirely unfeasible to draw a firm conclusion. Regulators are lagging in meeting the dire need of IBD patients, especially the elderly. Lack of legislation regarding registration, sales monitoring, licensing, insurance coverage, efficacy/safety assessments, post-marketing surveillance, quality assurance, and reference pricing alongside the limited support for CAM research are the main matters that should be urgently addressed.

Achieving Equitable Access to Medicines and Health Services: A COVID-19-time Recalled Matter.

In the 21st century, while some people seek to use artificial intelligence for health services delivery, others have to surrender their health rights to meet basic needs. The gradient in health has become more pronounced in the COVID-19 crisis considering discrepancies in disease prevalence, geographical accessibility, availability, affordability, quality/safety of health services, and human resources. Through PubMed, GoogleScholar, Scopus, WHO, OECD, and UN databases, the English documents and global statistics were collected. Determining the role of health equity-related factors and introducing mechanisms to maintain regional and international justice in health, specifically during the COVID-19 pandemic, were among the core concepts of this paper. Social determinants of health (SDH), interregional and intraregional bodies are the main drivers of discrimination in health services. Governments should relish chief health strategists' role in possessing legitimacy, accountability, direction, transparent performance, fairness, and good governance in one word. Improving health literacy and telemedicine, providing income support, and reforming insurance where needed, are other national mechanisms to amend inequity. Among interregional issues, what is concerning is the matter of sanctions on access to health services, which is against the Universal Declaration of Human Rights. Shortage of vital medications, ventilators, test kits, COVID-19 vaccines, pharmaceutical raw materials, foreign currency, decreased national currency value, purchasing power parity, and quality/safety of health services resulted from such oppression. The article also provides practical suggestions, paving the way for re-establishing global solidarity and developing health justice in deprived regions.

An overview of interventions for constipation in adults.

INTRODUCTION: The increasing global prevalence of the symptoms of constipation adversely affects the quality of life (QOL) of symptomatic patients. An acceptable universal definition of constipation does not exist and a detailed history taking form each patient with various complaints including stool consistency, sensing of incomplete evacuation or a manual need to assist evacuation is required. Complexity of obtaining etiologic diagnosis and the wide range of therapeutic options can mislead physicians in choosing correct treatment. AREAS COVERED: This review, considers the pathophysiology of constipation and the diagnostic approach to identify the etiology of constipation. Available interventions including non-pharmacological, pharmacological, and invasive methods such as acupuncture and surgical management are discussed. This review utilized on PubMed, Google Scholar, Scopus, and clinicaltrials.gov to search for studies and reviews published between 2000 and 2020. EXPERT COMMENTARY: Constipation necessitates careful considerations to detect the exact pathophysiology. Medical history, focused physical assessments, and selected diagnostic tests help choosing the right management. Non-pharmacological methods are beneficial in most of the cases. If a satisfactory response is not achieved, over the counter or prescribed medications are available. Options for patients who failed to respond to available medications are addressed in this review.

Assessment of arsenic-induced modifications in the DNA methylation of insulin-related genes in rat pancreatic islets.

Extended exposure to inorganic arsenic through contaminated drinking water has been linked with increased incidence of diabetes mellitus. The most common exposure occurs through the consumption of contaminated drinking water mainly through geogenic sources of inorganic arsenic. Epigenetic modifications are important mechanisms through which environmental pollutants could exert their toxic effects. Bisulfite sequencing polymerase chain reaction method followed by Sanger sequencing was performed for DNA methylation analysis. Our results showed that sodium arsenite treatment significantly reduced insulin secretion in pancreatic islets. It was revealed that the methylation of glucose transporter 2 (Glut2) gene was changed at two cytosine-phosphate-guanine (CpG) sites (-1743, -1734) in the promoter region of the sodium arsenite-treated group comparing to the control. No changes were observed in the methylation status of peroxisome proliferator-activated receptor-gamma (PPARγ), pancreatic and duodenal homeobox 1 (Pdx1) and insulin 2 (Ins2) CpG sites in the targeted regions. Measuring the gene expression level showed increase in Glut2 expression, while the expression of insulin (INS) and Pdx1 were significantly affected by sodium arsenite treatment. This study revealed that exposure to sodium arsenite changed the DNA methylation pattern of Glut2, a key transporter of glucose entry into the pancreatic beta cells (ß-cells). Our data suggested possible epigenetic-mediated toxicity mechanism for arsenite-induced ß-cells dysfunction. Further studies are needed to dissect the precise epigenetic modulatory activity of sodium arsenite that affect the biogenesis of insulin.

An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS), globally affecting 11.2% of the population and imposing a direct annual cost of $1.7bn-$10bn in the US, is one of the today's major therapeutic challenges. Therefore, there is urgent need to address this issue through reviewing the tolerability and efficacy of available medications. AREAS COVERED: Over the past decade, related experiments were cited through Clinicaltrials.gov, PubMed, WHO ICTRP, and Cochrane library. Pharmacological parameters of approved medications available in the USFDA, EMA, TGA and PMDA were also stated. EXPERT OPINION: Anti-spasmodics are used as the first-line treatment in pain-predominant IBS and IBS-D, among which calcium channel blockers and neurokinin-type 2 receptor antagonists seem to replace anti-cholinergic drugs. As second-line treatments, rifaximin is considered to be the best for IBS-D though it has lower efficacy than alosetron and eluxadoline. For IBS-C, linaclotide is the most effective and the safest second-line therapy, following laxatives/fibers, which may be replaced by tenapanor, in the future. When moderate to severe IBS is associated with severe pain or comorbid psychological disorders, gut-brain neuromodulators could also be prescribed. Regarding all this, there is still a paramount need to conduct careful clinical studies on efficacy, safety and cost-effectiveness of current approved and non-approved treatments.

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

Mechanistic assessment of cadmium toxicity in association with the functions of estrogen receptors in the Langerhans islets.

OBJECTIVES: Diabetes is a metabolic disease with an increasing prevalence for which finding new and efficient therapeutic approaches has always been a challenge. Preserving integrity and functionality of pancreatic ß-cells as the only source of insulin in the body is such a case. To achieve this goal different cellular targets have been proposed among which pancreatic estrogen receptors have gotten much attention. In this work, we evaluated the integrity and function of islets of Langerhans under the influence of factors known to intervene with estrogen receptors. Cadmium, a toxic heavy metal, has been recently shown to interact with estrogen receptors but its toxicity in the pancreatic islets regarding this mechanism remains unclear. MATERIALS AND METHODS: Isolated islets of Langerhans from the pancreas of rats were grouped and treated with cadmium chloride and also cadmium chloride plus ß-estradiol. After 24 hr incubation, parameters of cellular viability, oxidative stress, apoptosis, and insulin secretion were measured . RESULTS: The results indicated that cadmium reduced viability of the islets along with an increase in the formation of reactive oxygen species and apoptosis markers, and ß-estradiol, in turn, was able to alleviate these disturbances to some extent, implicating the protective role of ß-estradiol against pancreatic toxicity of cadmium. CONCLUSION: It can be concluded that modification of estrogen receptors in the endocrine pancreas and especially ß-cells may be a promising target to find a new therapeutic strategy for diabetes and even uncovering mechanisms of environmental toxicants that have been known as risk factors of diabetes.

Effectiveness of audit and feedback in addressing over prescribing of antibiotics and injectable medicines in a middle-income country: an RCT.

Overprescribing of antibiotics and injectable medicines is common in ambulatory care in many low- and middleincome countries. We evaluated the effects of three different interventions in improving physician prescribing. We conducted a four-armed randomized controlled trial with one-month and three- months follow-up. General physicians, pediatricians, and infectious disease specialists were included in this study if they had an outpatient office in Tehran, Iran. The study involved two behaviorally guided interventions: "new-design audit and feedback (NA&F)"; "printed educational material (PEM)" and an existing intervention of "routinely conducted audit and feedback (RA&F)". The theoretical framework underpinning the intervention was the theory of planned behavior. Main outcome measures were the percentage change in the proportion of prescriptions containing injectable dexamethasone; oral amoxicillin and cefixime. NA&F reduced the proportion of prescriptions particularly those containing dexamethasone injectable and cefixime (1.64, 0.99 absolute percentage change, p = 0.006, p = 0.01 respectively). PEM reduced the proportion of prescriptions containing cefixime (0.93 absolute percentage change p = 0.04). Other primary outcomes had no significant differences. A secondary outcome measure showed overall prescribing of injectables also reduced (absolute risk reduction: 3%). Overally, the study provides strong evidence that using theoretical insights in the development of the intervention improved prescribing behavior that lasted at least three months after the intervention. The design, format, and presentation of messages in feedback forms significantly influence the impact of audit and feedback on physician prescribing. While the interventions were effective, the impacts on inappropriate prescribing were modest and limited. In settings with rampant problems of overprescribing, intensive interventions are required to substantially improve prescribing patterns. Graphical abstract Graphical abstract.

The relationship between mercury exposure and epigenetic alterations regarding human health, risk assessment and diagnostic strategies.

BACKGROUND: Exposure to the environmental toxicants poses a serious threat to human health. The extent of exposure and the development of diseases are interrelated with each other. Chronic exposure to mercury (Hg) increases the risk of developing serious human disorders from embryo to adulthood. OBJECTIVES: The purpose of this review is to highlight the most common human disorders induced by Hg exposure on the basis of epigenetic mechanisms. A growing body of evidence shows that Hg exposure leads to alterations in the epigenetic markers. METHODS: We performed an organized search of the available literature using PubMed, Google Scholar, Medline, Reaxys, EMBASE and Scopus databases. All the relevant citations, including research and review articles in English were evaluated. The search terms included mercury, Hg, epigenetics, epigenetic alterations, DNA methylation, histone modifications, microRNAs (miRNAs), and risk assessment. RESULTS: Data on human toxicity due to Hg exposure shows broad variations in terms of chemical nature, doses, and the rate of exposure. Hg consumption either via foods or environmental sources may create deleterious health effects on various physiological systems at least partially through an epigenetic mechanism. CONCLUSION: Hg exposure could trigger epigenetic alterations, hence leading to various human disorders including reduced newborn cerebellum size, adverse behavioral outcomes, atherosclerosis and myocardial infarction. Similarly, in adults, occupational Hg exposure has been associated with an increased risk of autoimmunity. It has been revealed that miRNAs in the woman's cervix are a novel responder to maternal Hg exposure during pregnancy. Hg-induced epigenetic alterations analysis of kidney tissues showed a significant interruption in renal function. DNA methylation and histone post-translation modifications are predominant types of Hg epigenetic alterations.

Efficacy and safety of interleukin-1 antagonists in rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progression of the disease. Therefore, the aim of this study was to evaluate the clinical efficacy and safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis. Clinical trials and extension studies that compared anakinra with placebo or other medications were included. Electronic bibliographic databases: PubMed, Scopus, and Web of Sciences were searched from inception to November 2017. The American College of Rheumatology 20% (ACR20) improvement was the primary efficacy outcome measure. Total number of adverse drug events, serious adverse drug events, total treatment withdrawals, and treatment-related withdrawals were safety outcome measures. Ten studies were included in this review. One study did not fulfil quantitative criteria and was assessed qualitatively. Six clinical trials and three extension studies were included in meta-analysis. Patients treated with anakinra are 42% more likely to have ACR20 response than patients without IL-1Ra (pooled RR 1.42; 95% CI 1.01, 2.00). Patients on 30-150 mg anakinra have lower Health Assessment Questionnaire (HAQ) score than patients without IL-1Ra (SMD - 0.28; 95% CI - 0.53, - 0.03). The inflammatory marker erythrocyte sedimentation rate (ESR) was significantly lower among patients treated with 30-150 mg anakinra (SMD - 0.44; 95% CI - 0.65, - 0.23). Patients on anakinra have a 34% more risk of treatment-related withdrawal than placebo. The other parameters were not found to be statistically significant. Anakinra has a significant improvement in ACR20, HAQ, and ESR. The ACR20 response is maintained after 48 weeks of treatment. Anakinra shows higher episodes of treatment-related withdrawals than placebo.

Recent advances in biosensor technology in assessment of early diabetes biomarkers.

Discovery of biosensors has acquired utmost importance in the field of healthcare. Recent advances in biological techniques and instrumentation involving nanomaterials, surface plasmon resonance, and aptasensors have developed innovative biosensors over classical methods. Integrated approaches provided a better perspective for developing specific and sensitive devices with wide potential applications. Type 2 diabetes mellitus is a complex disease affecting almost every tissue and organ system, with metabolic complications extending far beyond impaired glucose metabolism. Although there is no known cure for Type 2 diabetes, early diagnosis and interventions are critical to prevent this disease and can postpone or even prevent the serious complications that are associated with diabetes. Biomarkers for type 2 diabetes are useful for prediction and intervention of the disease at earlier stages. Proper selection of biomarkers that represent health and disease states is vital for disease diagnosis and treatment by detecting it before it manifests. In this respect, we provide an overview of different types of biosensors being used, ranging from electrochemical, fluorescence-based, nanomonitors, SPR-based, and field-effect transistor biosensors for early detection and management of diabetes with focus on prediabetes. In the future, novel non-invasive technologies combined with blood and tissue-based biomarkers will enable the detection, prevention, and treatment of diabetes and its complications long before overt disease develops.

Pattern of Antidepressant Utilization and Cost in Iran from 2006 to 2013 in Comparison with Other Countries.

Antidepressant prescribing patterns have changed globally over the past few years, with conventional drugs including tricyclic antidepressants and monoamine oxidase inhibitors being replaced by selective serotonin reuptake inhibitors (SSRIs) and novel antidepressants. The objective of this study was to assess antidepressant utilization in Iran from 2006 to 2013 and to show Iran's situation in antidepressant consumption compared with other countries. A cross-sectional study was undertaken using prescription claims data from Iranian insurance agencies. In addition, total antidepressant sales data were obtained from the databank of the national regulatory authority. Medicines were classified according to the Anatomic Therapeutic Chemical (ATC-2012 edition) System. The Organisation for Economic Co-operation and Development data were used to compare national results from Iran with other countries. Antidepressant sales were four-fold higher than those of prescribed antidepressants [24 defined daily doses (DDD)/1000 inhabitants/day were sold whereas 6 DDD/1000 inhabitants/day were prescribed in 2013]. The trend in antidepressant prescriptions and consumption showed increasing use of SSRIs (N06AB). Nortriptyline, fluoxetine, and citalopram accounted for more than 60% of all prescriptions each year. The type of adverse reactions with new expensive antidepressants may seem convincing for the growing tendency toward using these medicines, but considering their high costs, health policymakers have to be aware of the risk of overprescription of newer antidepressant. Drivers of over-the-counter purchase of antidepressants need to be explored.

Ethics in Pharmacy Curriculum for Undergraduate Pharmacy Students: A Needs Assessment Study.

INTRODUCTION: Recent advances in pharmacy practice have created serious ethical challenges for the pharmacists. Pursuing a new philosophy of practice is required to overcome these challenges and optimize the standard of care. In this regard, the current ethics guideline in the Pharmacy curriculum used in Tehran University of Medical Sciences, does not provide a fully comprehensive understanding of the issue. Therefore, the aim of the present study was to revise the current curriculum based on a needs assessment study. METHODS: In this study, a two-part questionnaire was presented to pharmacists to obtain their views on the importance of topics in their daily routine practice. Part one of the questionnaire consisted of demographic data and part two of 23 topics in pharmacy ethics. RESULTS: Out of a total of 200 questionnaires, 158 questionnaires were returned. We reached consensus on 24 topics, of which 8 topics gained a score of higher than 4 (the highest score was considered to be 5) and the rest obtained a score of 3 and higher. The highest score pertained to the pharmacists' relationship with patients, awareness of the rules and regulations, and medication error. CONCLUSION: Based on the results, a revised curriculum was designed for ethics in pharmacy. It seems that the designed curriculum is context-based and will develop appropriate educational material regarding pharmacists' requirements in daily practice. Consideration of interactive methods for teaching the curriculum is highly recommended.

Growing knowledge of using embryonic stem cells as a novel tool in developmental risk assessment of environmental toxicants.

Developmental toxicology is an important area of novel toxicology. In recent years, there have been big concerns toward the increasing exposure to pharmaceutical agents, food additives, pesticides, occupational toxicants, and environmental pollutants, as well as their possible association with all aspects of male or female-mediated transient or permanent defects in progeny. Therefore, it is of great importance to look for new predictive models to evaluate environmental toxicants before they can harm the human health and embryo development. In this regard, new cell-based in vitro screening models have been developed and validated in predictive toxicology to minimize assay costs and animal usage. Stem cell-based models have been increasingly applied for predicting the toxicity of chemicals. One of the most promising existing in vitro developmental toxicity tests is the validated embryonic stem cell test (EST) which employs marine or human embryonic stem cells to assess the potential of chemicals embryotoxicity. These cells are very suitable for embryotoxicity assessment as they have been demonstrated to specify cellular developmental processes during early embryogenesis and gene expression patterns of differentiation to functionally competent specialized cell types. The present paper aimed at criticizing the human and experimental evidence for developmental toxic effects of environmental toxicants based on ESCs models. Accordingly, pesticides, heavy metals, plasticizers, nanomaterials and some solvents have been considered as the main evaluated environmental toxicants inducing developmental toxicity. At the end, current challenges, pros and cons of using ESCs as an alternative validated in vitro model for specific developmental toxicity screening are discussed.

Cost and Predictors of Hospitalizations for Ambulatory Care - Sensitive Conditions Among Medicaid Enrollees in Comprehensive Managed Care Plans.

INTRODUCTION: Preventable hospitalizations are responsible for increasing the cost of health care and reflect ineffectiveness of the health services in the primary care setting. The objective of this study was to assess expenditure for hospitalizations and utilize expenditure differentials to determine factors associated with ambulatory care - sensitive conditions (ACSCs) hospitalizations. METHODS: A cross-sectional study of hospitalizations among Medicaid enrollees in comprehensive managed care plans in 2009 was conducted. A total of 25 581 patients were included in the analysis. Expenditures on hospitalizations were examined at the 50th, 75th, 90th, and 95th expenditure percentiles both at the bivariate level and in the logistic regression model to determine the impact of differing expenditure on ACSC hospitalizations. RESULTS: Compared with patients without ACSC admissions, a larger proportion of patients with ACSC hospitalizations required advanced treatment or died on admission. Overall mean expenditures were higher for the ACSC group than for non-ACSC group (US$18 070 vs US$14 452). Whites and blacks had higher expenditures for ACSC hospitalization than Hispanics at all expenditure percentiles. Patient's age remained a consistent predictor of ACSC hospitalization across all expenditure percentiles. Patients with ACSC were less likely to have a procedure on admission; however, the likelihood decreased as expenditure percentiles increased. At the median expenditure, blacks and Hispanics were more likely than other race/ethnic groups to have ACSC hospitalizations (odds ratio [OR]: 1.307, 95% confidence interval [CI]: 1.013-1.686 and OR 1.252, 95% CI: 1.060-1.479, respectively). CONCLUSION: Future review of delivery and monitoring of services at the primary care setting should include managed care plans in order to enhance access and overall quality of care for optimal utilization of the resources.

Preclinical assessment of ß-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug.

CONTEXT: ß-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of ß-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far. OBJECTIVE: The study was designed to determine the acute and subchronic toxicity of ß-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively. MATERIALS AND METHODS: For the acute toxicity study, the animals received orally five different single doses of ß-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study. RESULTS: The results of acute toxicity indicated that the LD50 of ß-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats. CONCLUSIONS: Our results suggest that ß-D-mannuronic acid is relatively safe when administered orally in animals.