Use of prescription opioids in Israel and socio-economic correlations between 2010 and 2020.

BACKGROUND: The use of opioids has increased dramatically over the past several years in Israel. The aim of this study was to explore the trends of opioid consumption in Israel over a decade (2010-2020) stratified by socioeconomic status (SES), residence in the periphery, and ethnic background. METHODS: This cross-sectional study included all adult Maccabi Healthcare Services (MHS) patients who filled at least one prescription for opioids during the past decade. In order to standardize dosages and compare different opioid medications, we used the Morphine Milligram Equivalent (MME) conversion factor. We performed The Mann-Kendall test with autocorrelation correction to assess each trend. We then checked the differences between the trends with the Mann-Whitney test (for periphery) and the Kruskal Wallis (for SES and ethnic background). RESULTS: Between the years 2010-2020, 261,270 MHS members met the study's inclusion criteria. The proportions of opioids consumption were 23.9/1000 patients in 2010 and 27.6/1000 patients in 2020, representing a 15% increase. The average daily consumption of opioids was 4.6 and 10.5 MME in 2010 and 2020, respectively, an increase of 227%. The daily MME during 2020 was higher for residents of the periphery compared to non-periphery residents (daily MME of 14.0 compared to 10.1, respectively). Average daily MME increased gradually during the study period for all levels of SES; the values were highest for the low SES group and the lowest for the high SES group (daily MME in 2020 for the lowest, middle, and high SES groups were 15.2 vs. 11.8 vs. 6.7 respectively). CONCLUSIONS: This study highlights that the primary concern in the increase of opioid use is the increasing dosages. The increase in the number of patients using opioids is also significant but to a minor extent. These phenomena disproportionately impact vulnerable populations. Education programs should be offered to physicians regarding the possible harms of long-term use of opioids. These programs should emphasize the risk factors associated with the development of opioid use disorder (OUD) and the caution needed when increasing dosages or switching to higher-potency drugs. Pain clinics and centers for rehabilitation for patients with chronic pain or OUD should be available, not only in central areas but also in the periphery of the country. These clinics and centers should use a holistic approach and a multidisciplinary team that includes specialists in pain and addiction. They should be financially accessible for patients from low SES group and provide solutions in multiple languages.

Assessment of the response characteristics of pollution load in Huntai Basin under climate change.

This study establishes a calibrated SWAT (Soil and Water Assessment Tool) model for the Huntai Basin, driven by SSP126, SSP245, SSP585, and multi-model ensemble (MME) models in CMIP6 (Coupled Model Intercomparison Project-6), to investigate the effects of climate change on hydrological processes and pollution load in the Huntai Basin. The results show that the annual mean temperature and the annual precipitation will gradually increase. The nitrogen and phosphorus pollution loads in the basin exhibit a trend of decreasing-increasing-decreasing. The correlation between the nitrogen-phosphorus pollution load and the hydrological process strengthens with increasing radiative forcing. In the four scenarios, CO2 is a primary driving factor that contributes greatly to nitrogen and phosphorus pollution. The main differences are in the total driving factors, and SSP126 and SSP245 are less than those of other models. The total phosphorus and total nitrogen pollution in different climate models were higher than the average level during the benchmark period, except for ammonia nitrogen pollution, which was lower. The nitrogen and phosphorus pollution in SSP126 and SSP245 modes will reach the maximum in 2040s, and the pollution in other periods will be lower than that in SSP585 and MME scenarios. In the long run, the development state between SSP126 and SSP245 may be better appropriate for the Huntai Basin's future sustainable development. This paper analyzes the occurrence and influencing factors of nitrogen and phosphorus pollution under climate change to provide reference to the protection of water environment under changing environments.

Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.

High Density Supercritical Carbon Dioxide for the Extraction of Pesticide Residues in Onion with Multivariate Response Surface Methodology.

The excessive use of pesticides is a serious health problem due to their toxicity and bioaccumulation through the food chain. Due to the complexity of foods, the analysis of pesticides is challenging often giving large matrix effects and co-extracted compounds. To overcome this problem, a selective and "green" supercritical fluid extraction method was developed, using neat carbon dioxide as a solvent at pressures of up to 800 bars. A Box-Behnken response surface experimental design was used, with the independent variables of density (0.70-1.0 g mL-1), temperature (40-70 C), and volume (10-40 mL) of solvent, and the dependent variable of extracted amount of pesticides. The optimum extraction condition was found at the use of 29 mL of supercritical CO2 at 0.90 g mL-1 and 53C (corresponding to 372 bars of pressure). It was observed that increasing the density of CO2 significantly increased the extraction recovery of endrin and 2,4'-dichlorodiphenyldichloroethane. Matrix-matched calibration curves showed satisfactory linearity (R2 ≥ 0.994), and LODs ranged from 0.2 to 2.0 ng g-1. Precision was lower than 11% and recoveries between 80%-103%. Thus, the developed method could efficiently be used for trace analysis of pesticides in complex food matrices without the use of organic solvents.

[Effect of acupuncture along affected meridian on the MME gene expression of migraine patients without aura of gan-yang hyperactivity syndrome].

OBJECTIVE: To observe the effect of acupuncture along affected meridian on the mem- brane metallo-endopeptidase (MME) gene expression of migraine patients without aura (MO) of Gan-yang hyperactivity syndrome (GYHS). METHODS: Totally 20 MO patients of GYHS were randomly assigned to the acupoint group (acupuncture along affected meridian) and the non-acupoint group, 10 cases in each group. Needling was performed once per day for 10 consecutive days. Gene chip technology was used to obtain two sets of gene expression profiles and analyzed using Gene Ontology (GO). RESULTS: In the acupoint group, MME gene expression decreased after needling (P = 0.0023).That gene was rich in the beta-amyloid metabolic process (P = 3.16E-05) and the peptide metabolic process (P = 0.009612). Its expression was not seen in the non-acupoint group. CONCLUSION: The effect of point selection along affected meridian could be achieved possibly by regulating the MME gene expression.

Effect of acupuncture along affected meridian on the MME gene expression of migraine patients without aura of gan-yang hyperactivity syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of acupuncture along affected meridian on the mem- brane metallo-endopeptidase (MME) gene expression of migraine patients without aura (MO) of Gan-yang hyperactivity syndrome (GYHS).</p><p><b>METHODS</b>Totally 20 MO patients of GYHS were randomly assigned to the acupoint group (acupuncture along affected meridian) and the non-acupoint group, 10 cases in each group. Needling was performed once per day for 10 consecutive days. Gene chip technology was used to obtain two sets of gene expression profiles and analyzed using Gene Ontology (GO).</p><p><b>RESULTS</b>In the acupoint group, MME gene expression decreased after needling (P = 0.0023).That gene was rich in the beta-amyloid metabolic process (P = 3.16E-05) and the peptide metabolic process (P = 0.009612). Its expression was not seen in the non-acupoint group.</p><p><b>CONCLUSION</b>The effect of point selection along affected meridian could be achieved possibly by regulating the MME gene expression.</p>

[Anti tumor activities of lentinan and micellapist in tumor-bearing mice].

Although Lentinan (LNT) is sold as a medicine, and Micellapist (MME) sold as a food supplement, both LNT and MME are beta-glucans isolated from the Shiitake mushroom (Lentinula edodes). These two substances have been thought to be the same component of Shiitake. In the present study, we evaluated anti tumor activities of LNT and MME in tumor-bearing mice (B10.D2 mice implanted with S908D2 tumor cells) and examined the mechanism of immunopotentiation of these substances. The tumor growth was significantly suppressed in the LNT-treated group. In ex vivo evaluation, the tumor cytotoxicity was significantly reduced by a treatment of splenocytes with anti-CD8 antibody in the LNT-treated group. Furthermore, the tumor cytotoxicity of the LNT-treated group was also significantly reduced by a treatment of splenocytes with anti-CD8 antibody and its complement and with an anti-CD4 and its complement in the effector phase and the induction phase, respectively. A significant prolongation of the survival of tumor-bearing mice as compared to the untreated control group was noted in the LNT-treated group. In the mice treated intraperitoneally with LNT, CD8-positive cells appeared to have suppressed tumor cell proliferation. CD4-positive cells appeared to be involved in this activity of CD8-positive cells. On the other hand, orally administered MME has exerted no clear cytotoxic effects.

Endrin-induced depletion of glutathione and inhibition of glutathione peroxidase activity in rats.

1. Recent studies have shown that endrin induces lipid peroxidation and may produce toxicity through an oxidative stress. We have therefore examined the effect of endrin administration to rats on glutathione content and the activities of glutathione metabolizing enzymes. 2. The oral administration of endrin resulted in dose- and time-dependent decreases in hepatic and renal glutathione content with maximum depletion (90%) occurring in liver at approximately 24 hr post-treatment. 3. Decreases in glutathione content were also observed in lung, brain, spleen and heart. 4. Endrin (4 mg/kg) decreased selenium dependent glutathione peroxidase activity in liver and kidney by 64 and 50%, respectively, while small increases were observed in the activities of glutathione reductase and glutathione S-transferase. 5. The toxicity of endrin may be at least in part related to oxidative tissue damage associated with depletion of glutathione and inhibition of glutathione peroxidase activity.

The science of teratology in a regulatory setting.

The science of teratology is discussed from a regulatory point of view. A brief history of this branch of toxicology is presented with emphasis on specific instances of the inadvertent production of birth defects in humans as a result of exposure to exogenous agents. The basic principles of teratology are elucidated as a means of understanding current test protocols and their scientific rationale. A typical, general protocol is given and some of the major shortcomings of such a bioassay are presented. Among these shortcomings are the problems of significance of fetal toxicity and lack of a postnatal component to the teratology test system. The teratogenic and/or fetotoxic potential of selected pesticides are examined with special reference to the bioassay problems alluded to. Pesticides discussed include cacodylic acid, endrin, benomyl, ETU, nitrofen, and mirex. Finally, a brief discussion of a proposed teratology screen using pregnant laboratory animals is presented.

Short-term effect of two pesticides on the survival, ovarian 32P uptake and gonadotrophic potency in a freshwater catfish, Heteropneustes fossilis (Blouch).

The effects of pesticides containing either an organophosphate malathion (Cythion) or an organochloride endrin (Hexadrin) on the survival, ovarian 32P uptake and the gonadotrophic potency of the pituitary gland and serum of Heteropneustes fossilis were studied for 96 h. Hexadrin was found to be more toxic than Cythion. Reduced ovarian 32P uptake and a significantly decreased level of total gonadotrophin in the pituitary gland and serum were seen when fish were placed either in a drug concentration that had been found to kill half the fish in 96 h or in a safe concentration of Hexadrin and cythion in aquarium water. Administration of LH or homologous pituitary extract during the exposure of the fish to the pesticides increased the ovarian 32P uptake. The data suggest that these pesticides retarded gonadotrophin secretion which in turn reduced ovarian 32P uptake. However, they did not interfere with the effects of exogenous LH or pituitary extract at the dose levels tested.

Effect of spraying developed shoot system with insecticide "endrin" on rhizosphere mycoflora of both okra and lupins.

Spraying shoot system of okra and lupins plants with insecticide endrin caused changes in plant metabolism. These changes reflected themselves on root exudates. Accordingly, the balance between the higher plant and the fungal population in the root zone was disturbed.

A critical review of currently used single-dose rodenticides.

The introduction of the anticoagulants in the early 1950s, with their much greater safety to nontarget animals, resulted in a general decline in the use of single-dose rodenticides. However, the appearance of rodent resistance to the anticoagulants, first in the United Kingdom, later elsewhere in Europe, and still more recently in the USA, has revived interest in the use of single-dose rodenticides. Unfortunately, owing to their danger to nontarget mammals, the use of several of these compounds must be restricted; others, despite their long use, are now recognized to be unsatisfactory because of their poor acceptance or reacceptance by rats and mice. Thus, only very few compounds of this type are available for unrestricted use and there is an urgent need for the development of effective alternatives.