Most Pb and Cd neurotoxicity studies investigate exposure to either of the toxic metals alone, while data on co-exposure are scarce. The aim of our study was to fill that gap by investigating acute ...combined effects of Pb and Cd on redox and essential metal status in the brain of Wistar rats. Animals were randomised in four groups of six to eight rats, which received 15 or 30 mg/kg of Cd, 150 mg/kg of Pb, or 150 mg/kg of Pb + 15 mg/kg of Cd by gavage. The fifth, control, group received distilled water only. Co-treatment with Pb and Cd induced significant increase in malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) compared to control and groups receiving either metal alone. This is of special importance, as MDA presence in the brain has been implicated in many neurodegenerative disorders. The groups did not significantly differ in Zn, Cu, Mn, and Fe brain levels. Our findings highlight the importance of metal mixture studies. Neurotoxicity assessments of single chemicals do not provide a real insight into exposure to mixtures in real life. Further research should look into interactions between these metals to reveal complex molecular mechanisms of their neurotoxicity.
Lead (Pb) is a toxic metal that affects almost all human's system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity ...requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.
•Lead-low doses affected memory in rats that was related to inhibition of acetylcholinesterase.•Hyperactivity and dose-dependent induction of oxidative stress and Zn elevation was obtained.•The lowest BMD was calculated for total oxidative status (4.5e-06 mg Pb/kg b.w./day).•The obtained results provide useful data for further evaluation of referent point of Pb.
Immunochromatographic strips for urine drug screening tests (UDSTs) are common and very suitable for drug abuse monitoring, but are also highly susceptible to adulterants kept in the household, which ...can significantly alter test results. The aim of this study was to see how some of these common adulterants affect UDST results in practice and whether they can be detected by sample validity tests with pH and URIT 11G test strips. To this end we added household chemicals (acids, alkalis, oxidizing agents, surfactants, and miscellaneous substances) to urine samples positive for amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), tetrahydrocannabinol, heroin, cocaine, or benzodiazepines (diazepam or alprazolam) and tested them with one-component immunochromatographic UDST strips. The UDST for cocaine resisted adulteration the most, while the cannabis test produced the most false negative results. The most potent adulterant that barely changed the physiological properties of urine specimens and therefore escaped adulteration detection was vinegar. Besides lemon juice, it produced the most false negative test results. In conclusion, some urine adulterants, such as vinegar, could pass urine specimen validity test and remain undetected by laboratory testing. Our findings raise concern about this issue of preventing urine tampering and call for better control at sampling, privacy concerns notwithstanding, and better sample validity tests.
: We conducted a comparative assessment of the productivity loss associated with the two different treatment options for Dupuytren's disease: collagenase and fasciectomy.
: The retrospective claims ...analysis was performed using the data from IBM MarketScan® Commercial (CD) and Health and Productivity Management (HPM) Databases over five years (2012-2016). We identified two cohorts of patients who underwent either collagenase or fasciectomy in the CD. Propensity-score matched patients were linked to their productivity loss claims in the HPM database. Productivity loss measures were assessed over a 12-month follow-up period.
: Out of 702 collagenase and 999 fasciectomy propensity score-matched patients in the CD, there were 147 collagenase and 273 fasciectomy patients in the HPM database. Over the follow-up period, collagenase-treated patients were significantly less likely to use short-term disability (STD) leave (9.7% vs. 20.2%;
= 0.009), reflecting in the lower average number of absent STD days (mean, 2.8 vs. 8.1;
= 0.002) in comparison to fasciectomy-treated. The mean indirect STD cost was considerably lower in the collagenase vs. fasciectomy group ($375 vs. $1,108;
= 0.002).
: This study indicates that collagenase vs. fasciectomy treatment may be related to a lower rate of workplace absence and lower indirect cost in a year following the treatment.
Zah V, Pelivanovic J, Tatovic S, et al. ClinicoeconOutcomes Res. 2020;12:635-643. The authors have advised that the Disclosure statement onpage 642 is incorrect. The first sentence "Vladimir ...Zah,Djurdja Vukicevic, and Martina Imro are employees ofZRx Outcomes Research Inc. (institution founded byEndo Pharmaceuticals to conduct the present analysis),and have received grants from Endo PharmaceuticalsInc" should read "Vladimir Zah, Djurdja Vukicevic, andMartina Imro are employees of ZRx Outcomes ResearchInc. (institution funded by Endo Pharmaceuticals to conductthe present analysis), and have received grants fromEndo Pharmaceuticals Inc". The authors apologize for this error. Read the original article
Studies examining differences in US healthcare resource utilization (HCRU) and associated healthcare costs between collagenase clostridium histolyticum (CCH) and fasciectomy for Dupuytren contracture ...(DC) are limited. This study evaluated US HCRU and direct healthcare cost for the treatment of DC in privately insured patients using insurance claims.
This retrospective observational cohort study analyzed data from large nationwide insurance claims databases; it included individuals diagnosed with DC between July 1, 2011, and June 30, 2017, who were adults at index date (date of first treatment: CCH or fasciectomy). Participants had continuous health plan coverage 24 months pre-index and 12 months post-index date. All-cause and DC-related HCRU and healthcare costs from the payers' perspective were compared between propensity score-matched cohorts. Generalized linear models assessed factors associated with all-cause total healthcare costs.
Of 83,983 patients diagnosed with DC, 1932 adults receiving fasciectomy and 953 adults receiving CCH were included. The mean ± standard deviation total all-cause healthcare cost was significantly lower with CCH than with fasciectomy (US$11,897 ± US$14,633 versus US$15,528 ± US$22,254, respectively;
<0.001). After propensity score matching, 702 and 999 patients remained in the CCH and fasciectomy cohorts, respectively. In this analysis, all-cause and DC-related total costs were significantly lower in the CCH cohort versus the fasciectomy cohort (all-cause: US$11,044 ± US$12,856 versus US$12,912 ± US$19,237, respectively,
=0.02; DC-specific: US$3417 ± US$3671 versus US$5800 ± US$4985,
<0.001), mainly due to the lower frequency of outpatient visits. CCH treatment and the use of a consumer-driven healthcare plan were associated with lower healthcare costs.
Based on matched cohort data, adjusted 1-year healthcare costs for CCH-treated individuals were significantly lower compared with costs for fasciectomy-treated individuals.
Chronic pain treatment imposes a substantial economic burden on US society. Treatment costs may vary across subgroups of patients with different types of pain. The aim of our study was to compare ...healthcare costs (HC) and resource utilization in musculoskeletal (MP), neuropathic (NP), and cancer pain (CaP) patients treated with long-acting opioids (LAO), using real-world evidence.
We compared total HC and resource utilization in subgroups of chronic pain patients (MP, NP or CaP) treated with three LAO alternatives: morphine-sulfate extended-release (MsER), oxycodone ER (OxnER) and tapentadol ER (TapER). Retrospective claims data were analyzed in the IBM Truven Health MarketScan
Commercial Claims Database (October 2012 through March 2016). All patients were continuously health plan enrolled for at least 12 months before the index date (first LAO prescription date) and during the LAO-treatment period. The cohorts were propensity-score matched.
A total of 2824 TapER-treated patients were matched to 16,716 OxnER-treated patients, while 2827 TapER patients were matched to 16,817 MsER patients. The average monthly total HC were lower in the TapER than in the OxnER cohort ($2510 vs. $3720, p<0.001), reflecting significantly lower outpatient, inpatient and emergency department visit rates in the TapER cohort. Similarly, the TapER cohort exhibited a lower average monthly total HC ($2520 vs. $2900, p<0.05) than MsER cohort, with significantly fewer inpatient and outpatient visits in the TapER cohort. TapER demonstrated significantly lower total HC than OxnER in patients with NP and MP, and similar to OxnER in CaP patients. TapER costs were similar to MsER costs in all pain-type subpopulations.
Based on real-world evidence, the TapER treatment for chronic pain was associated with significantly lower HC compared with MsER or OxnER. When categorized by type of pain, TapER remained a less costly strategy in comparison with OxnER for MP and NP.
Preliminarna analiza prisutnosti psihoaktivnih tvari u mokraći pomoću imunokromatografskih testnih traka (UDST) našla je primjenu u mnogim područjima. Iako vrlo prikladne u kontroli zloporabe droga, ...testne su trake iznimno osjetljive na sredstva za patvorenje (adulterante) kao što su kućne kemikalije, što može značajno promijeniti rezultate testa. Cilj ovoga istraživanja bio je ispitati potencijal uobičajeno korištenih adulteranata kada je riječ o utjecaju na rezultate probira na prisutnost psihoaktivnih tvari u mokraći uporabom UDST-a. Ispitivane kemikalije (kiseline, lužine, oksidirajuća sredstva, površinski aktivne tvari i druge) dodane su uzorcima urina u kojima je, tekućinskom kromatografijom – masenom spektrometrijom (LC-MS) prethodno potvrđena prisutnost amfetamina, 3,4-metilendioksimetamfetaina (MDMA), tetrahidrokanabinola, heroina i kokaina benzodiazepina (diazepam ili alprazolam). U ispitivanju su korištene jednokomponentne imunokromatografske testne trake. Manipulacija uzorcima urina provjeravala se pomoću pH traka, kao i biokemijskih testnih traka za semikvantitativno određivanje koncentracija endogenih tvari i specifične težine uzoraka urina pomoću testnih traka URIT 11G. Rezultati ovoga ispitivanja pokazali su da je test za detekciju kokaina u urinu najmanje osjetljiv na utjecaj ispitivanih adulteranata, a test za detekciju kanabinoida najosjetljiviji, posebice u pogledu lažno negativnih rezultata. Najsnažniji adulterant koji je utjecao na rezultate testa a nije promijenio fiziološke parametre urina je alkoholni ocat. Osim soka od limuna, alkoholni ocat dodan u urin proizveo je najveći broj negativnih ishoda testiranja. Može se zaključiti da značajan broj adulteranata utječe na rezultate testa i da je moguće da neki od njih, poput alkoholnoga octa, mogu proći neopaženo pri kontroli valjanosti uzorka. Ovi nalazi upozoravaju na važnost strogo kontroliranog okruženja za uzorkovanje urina kako bi se spriječile manipulacije.
Dosadašnji podatci o neurotoksičnosti olova (Pb) i kadmija (Cd) uglavnom su opisani nakon izloženosti pojedinačnim metalima, a podatci o neurotoksičnom djelovanju smjese tih dvaju metala prilično su ...oskudni. Cilj ovoga rada bio je ispitati učinak akutnoga izlaganja smjesi olova i kadmija na parametre oksidacijskoga stresa i status bioelemenata u mozgu štakora. Životinje su bile podijeljene u pet skupina: Cd15 (15 mg/kg), Cd30 (30 mg/kg), Pb150 (150 mg/kg), Pb150+Cd15 i kontrolna, netretirana skupina. Smjesa olova i kadmija dovela je do značajno viših vrijednosti malondialdehida (MDA) i drugih produkata u mozgu štakora u usporedbi s kontrolnom skupinom i obama pojedinačnim metalima. To je iznimno važno, imajući u vidu da je prisutnost MDA-a u mozgu povezana s mnogim neurodegenerativnim poremećajima. Nije dobivena statistički značajna razlika između ispitivanih skupina u razinama cinka (Zn), bakra (Cu), mangana (Mn) I željeza (Fe). Rezultati ovoga istraživanja važan su doprinos budućim istraživanjima smjesa i upućuju na to da istraživanja toksičnosti u kojima se procjenjuje neurotoksičnost pojedinačnih kemikalija ne pružaju stvarni uvid u neurotoksičnost njihovih smjesa kojima smo izloženi u stvarnom životu. Dobiveni rezultati otvaraju daljnja pitanja o interakciji i mehanizmima toksičnosti smjese tih metala.
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