Treatment of primate platynosomosis: A word of caution about the use of praziquantel in marmosets.

BACKGROUND: The successive reports of Platynosomum illiciens in Neotropical captive primates have increased interest in platynosomosis; however, its treatment is little known. METHODS: Callithrix penicillata (n = 10) naturally and chronically infected with P. illiciens were treated with praziquantel (25 mg/kg BW, three s.c. doses at 24 hours intervals), and coproparasitological tests performed over 67 days. The proportions of primates with a reduction in fecal egg counts (FEC) or negative results progressively increased after treatment, and at the last fecal tests, marmosets were negative. RESULTS AND CONCLUSIONS: Although all primates tolerated the initial days of study well, 40% (4/10) of them died between the 8th and 16th days after the onset of treatment. Clinical signs and necropsies indicated the occurrence of hepatic involvement, biliary obstruction, and cholangitis. Marmosets with a higher previous FEC were more likely to die after treatment. Use of praziquantel should be considered carefully on a case-by-case basis.

Adverse effects of routine bovine health treatments containing triclabendazole and synthetic pyrethroids on the abundance of dipteran larvae in bovine faeces.

Macrocyclic lactone treatments for livestock can have detrimental effects on the arthropod populations in livestock faeces. For the last twenty years, avoidance of these products has been a standard recommendation on livestock farms that are managed for wildlife by the Royal Society for Protection of Birds (RSPB). However, the continued decline in the populations of birds (in particular the red-billed chough Pyrrhocorax pyrrhocorax) that are dependent on dung invertebrates on islands in the Inner Hebrides of Scotland prompted us to investigate the effects of livestock treatments that are commonly used on these islands. We conducted a replicated field plot study over two years to quantify the effects of livestock treatments containing copper, deltamethrin and triclabendazole on invertebrate density in pooled, artificial faecal pats on the island of Islay. We found that the density of arthropod larvae was significantly reduced by the triclabendazole and deltamethrin treatments in both years and by as much as 86% when the treatments were combined. Copper-containing boluses did not consistently affect abundance of arthropod larvae. These results suggest that veterinary treatment of livestock might contribute to a reduction in the food supply of chough.

Quality of Vitamin K Antagonist Control and 1-Year Outcomes in Patients with Atrial Fibrillation: A Global Perspective from the GARFIELD-AF Registry.

AIMS: Vitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0-3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality. METHODS AND RESULTS: TTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027). CONCLUSION: A large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01090362.

High risk use of OTC NSAIDs and ASA in family medicine: A retrospective chart review.

BACKGROUND: Complications associated with the use of NSAIDs, antiplatelet agents, and anticoagulants are among the top causes of preventable drug-related ER visits, hospitalizations and death. Although over-the-counter (OTC) NSAIDs and ASA also contribute to this preventable risk, it is unclear how well these medications are documented in primary care records. METHODS: A retrospective electronic and paper chart review was conducted to evaluate the prevalence of 13 evidence-based high-risk prescriptions and the contribution of OTC NSAIDs and ASA to these potentially inappropriate prescriptions (PIPs). RESULTS: Of the 148 patients included in the review, ASA was taken by 117 patients (79%) while OTC NSAIDs were taken by 36 (24%). OTC NSAIDs were never documented within the "medication" section of the electronic record, whereas ASA was documented in 65 (56%) cases. Eighty percent (118/148) taking either OTC NSAIDs or ASA were identified as having at least one PIP. CONCLUSION: OTC NSAIDs and ASA are widely available and are commonly taken without the knowledge of the prescriber. These medications contribute to the overall risk of bleeding. Review and documentation of OTC NSAIDs and ASA use should be part of all relevant patient encounters when prescribing NSAIDs, antiplatelets and anticoagulants.

Efficacy and safety of antiplatelet-combination therapy after drug-eluting stent implantation.

BACKGROUND/AIMS: Combination single-pill therapy can improve cost-effectiveness in a typical medical therapy. However, there is a little evidence about the efficacy and tolerability of combination single-pill antiplatelet therapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: From June to November 2012, in total, 142 patients who met the following criteria were enrolled: at least 18 years old; successful PCI with DES at least 3 months earlier; and regular medication of aspirin and clopidogrel with no side effects. After VerifyNow P2Y12 and aspirin assays, the combination single pill of aspirin and clopidogrel was given and laboratory tests were repeated 6 weeks later. RESULTS: At baseline, the incidence of aspirin resistance, defined as aspirin reaction unit (ARU) ≥ 550, was 9.2%, that of clopidogrel resistance, defined as P2Y12 reaction unit (PRU) ≥ 230, was 46.5%, and that of percent inhibition of PRU < 20% was 32.4%. At follow-up, the incidence of resistance by ARU value was 7.0%, 50.0% by PRU value, and 35.9% by percentage inhibition of PRU, respectively. The mean values of ARU (431.5 ± 63.6 vs. 439.8 ± 55.2; p = 0.216) and PRU (227.5 ± 71.4 vs. 223.3 ± 76.0; p = 0.350) were not significantly different before versus after antiplatelet-combination single-pill therapy. Five adverse events (3.5%) were observed during the study period. CONCLUSIONS: Combination single-pill antiplatelet therapy, which may reduce daily pill burden for patients after PCI with DES, demonstrated similar efficacy to separate dual-pill antiplatelet therapy.

Platelet function testing in patients with acute coronary syndrome.

In patients with an acute coronary syndrome (ACS), inhibition of the platelet P2Y12 receptor is standard of care. The shortcomings of the most commonly used P2Y12 receptor inhibitor clopidogrel-that is its delayed onset of action, its interindividual response variability, and the phenomenon of high on-treatment platelet reactivity-led to the development of more potent P2Y12 receptor inhibitors (prasugrel and ticagrelor) that proved their superiority in terms of reducing thrombotic events compared to clopidogrel. Available randomized studies that aimed at investigating the value of a personalized antiplatelet treatment regimen based on platelet function monitoring results were negative with regard to the possible benefits of monitoring but were all limited by mainly enrolling elective and stable patients with coronary artery disease. Thus, it still warrants further investigation if a tailored, platelet function guided, antiplatelet therapy in ACS patients with the available P2Y12 receptor inhibitors prasugrel, ticagrelor, and clopidogrel can lead to improved patients outcome.

Synthesis and anthelmintic activity of osthol analogs against Dactylogyrus intermedius in goldfish.

In an attempt to develop novel anthelmintic agents, our previously isolated osthol was used as lead structures for further optimization. In our research, a series of coumarin analogs, prepared from 7-hydroxy coumarin or 7-hydroxy-4-methyl coumarin, have been evaluated for their anthelmintic activities. In all of the compounds, 6 and 7 were first synthesized, and their structures were identified based on NMR and MS values. Among the candidates, 8-allyl-7-allyloxycoumarin showed better anthelmintic activity than other compounds against Dactylogyrus infestation with EC(50) value of 1.81 mg/L. The quantitative structure-activity relationship (QSAR) of 16 osthol analogs with anthelmintic activity expressed as pEC(50) and toxicity to goldfish expressed pLC(50), such results can offer useful theoretical references for future experimental works.

Anthelmintic activity of artesunate against Fasciola hepatica in naturally infected sheep.

In light of rapidly spreading triclabendazole resistance alternative fasciocidal drugs are urgently needed. Following up on promising results obtained with artemether in Fasciola hepatica infected sheep, we here report the efficacy and safety of artesunate in sheep with a natural F. hepatica infection. Artesunate was administered intravenously and intramuscularly, adverse events were monitored and drug efficacy was elucidated by means of faecal egg and worm burden reductions. A single 40 mg/kg intravenous dose of artesunate induced an egg count reduction of 68.9% and a worm burden reduction of 77.4%. Intramuscular artesunate at 40 mg/kg reduced faecal egg count and worm burden by 97.6% and 91.9%, respectively; whereas at 60 mg/kg it caused 93.2% and 87.1% reduction in faecal egg count and worm burden, respectively. Three sheep died 24-72 h post-treatment with a double dose of 40 mg/kg intramuscular artesunate, showing lethargy, sialorrhoea, reduced rumination and tremors. Egg and worm burden reductions of 93.3% and 83.9%, respectively, were calculated in the three surviving sheep. In conclusion, the interesting fasciocidal properties of artesunate in sheep warrant further investigations with an emphasis on toxicity studies.

The effect of antiplatelet drugs clopidogrel and aspirin is less immediately after stent implantation.

INTRODUCTION: A decreased effect of clopidogrel or aspirin on platelets corresponds to an increased risk of major adverse coronary events. The aim was to investigate if the inhibition of platelet function by clopidogrel and aspirin is equal at two different time points: immediately after percutaneous coronary intervention (PCI) and one day thereafter. MATERIALS AND METHODS: Platelet function was assessed by the Vasodilator Stimulated Phosphoprotein (VASP) phosphorylation assay, Impedance Aggregometry, Platelet Function Analyzer and the Cone and Platelet Analyzer in 30 patients on chronic treatment with clopidogrel and aspirin. RESULTS: Inhibition of platelets by clopidogrel and aspirin was less post PCI than one day after PCI as measured with the VASP assay and aggregometry: the platelet reactivity index, the adenosine diphosphate/prostaglandin and the arachidonic acid -induced platelet aggregation were 23% (p=0.009), 75% (p=0.001) and 127% (p<0.001) higher post PCI than one day after PCI, respectively. The collagen/adenosine diphosphate closure time was 30% higher after PCI compared to one day thereafter (p=0.047), which could in part be due to a two-fold increase in von Willebrand factor-ristocetin cofactor activity one day after PCI (p=0.001). CONCLUSION: Inhibition of platelets by clopidogrel and aspirin was less immediately post PCI as compared to one day thereafter. This indicates that the time point of platelet function testing is important for the determination of cut-off points and the definition of nonresponsiveness to antiplatelet drugs.

Long-term evaluation of patients with hydatidosis treated with albendazole and praziquantel.

Hydatidosis is a usually asymptomatic chronic disease. In most patients who undergo surgery, hydatidosis is not resolved due to high recurrence rate. However, long-term treatment with albendazole has been found to have a significant efficacy that has been further improved when albendazole is combined with praziquantel and fat-rich diet. In this study a retrospective evaluation of the outcome of hydatidosis in 70 patients, was performed. In group A, a combined chemotherapy of albendazole plus praziquantel was given after surgical removal of cysts. In group B chemotherapy alone was administered without surgery. Sera of all patients were assayed for IgG, IgM, IgA and IgE antibodies by ELISA. In addition, ultrasonography (US) and/or computerized tomography (CT) scans were performed every 3 months for 18 months, and then, each year until the end of follow-up. The difference between the two kinds of treatment used in the present study was found to be not significant, nor was the difference of the shrinkage and extended calcification of the HCs between the two groups. However, the difference of the shrinkage of the HCs of more than 80%, as well as the extended calcifications of the cysts between the two groups were found to be statistically significant. In all patients high levels of IgG and IgA were detected, while IgE in group A and/or IgM in group B were marginally detected above the background level throughout the study. Level of IgG was strongly fluctuated and significantly decreased at 11.7 years after the end of chemotherapy, or at 8.5 years after relapses in group A, while was dramatically decreased at 3.6 years after the termination of chemotherapy in group B. Relapses occurred in 11.4% of patients within the first six months after end of chemotherapy. After additional chemotherapy with albendazole for 3-6 months, all of them were considered cured at 8.5 years of follow up.

[Preclinical studies of cucurbita maxima (pumpkin seeds) a traditional intestinal antiparasitic in rural urban areas]. / Estudios preclínicos de cucurbita máxima (semilla de zapallo) un antiparasitario intestinal tradicional en zonas urbano rurales.

Experimental research was carried out at the Parasitology and Chemistry laboratories of the Jorge Basadre Grohmann National University, in Tacna. The process involved two phases: (1) determination of the minimum inhibitory concentration (MIC) of Cucurbita Maxima as an antiparasitic agent using canine tapeworms with an intestinal isolation of 5 to 6 hours, and (2) determination of the side-effects of Curbita Maxima on exposed albino rats. It was found that the MIC of 23 gr. of pumpkin seed in 100 ml. of distilled water can produce an antihelminthic effect. This concentration is equivalent to +/- 73 pumpkin seeds (x2 = 5.6, p<0.01). Macroscopically, alterations in helminthic motility are present at a dose of > 23 gr. There is a protheolithic effect with an average survival time of 38.4 minutes. Microscopically the mature proglottids present a destruction of the tegument involving the basal membrane. In the gravid proglottids there is egg destruction. These findings are accentuated when experimenting with Cucurbita Maxima in a concentration of 30 and 32 gr. Superficial non-erosive gastritis was found in weys rats after 4 hours of administering 9 gr/kg.

Large cerebral infarction during praziquantel therapy in neurocysticercosis.

BACKGROUND: Large cerebral infarction is a rare complication of neurocysticercosis. Endarteritis by inflammation of the leptomeninges is known to be its cause. CASE DESCRIPTION: A 59-year-old man with known neurocysticercosis developed a large cerebral infarction during praziquantel therapy. A follow-up MRI obtained immediately after his cerebral infarction demonstrated notable decrease in the size of the cysts and more prominent enhancement around the peripheral margins of the cysts and the major vessels in comparison with the initial MRI. Cerebral angiography disclosed occlusions and narrowing of both internal carotid arteries at the supraclinoid portions, where multiple cysts were found on the MRI. CONCLUSIONS: Findings in our patient strongly suggest that a secondary inflammation reaction caused by the destruction of the cysts might have enhanced the process of endarteritis. The possible deleterious effects of praziquantel therapy should be considered in the treatment of patients with subarachnoid cysticerci.

[The procedure for the wide use of praziquantel in a complex of measures to control opisthorchiasis. 2. The tolerance and efficacy of Russian-made azinox in mass treatment in foci]. / Taktika shirokogo primeneniia prazikvantelia v komplekse mer bor'by s opistorkhozom. Soobshchenie 2. Perenosimost' i éffektivnost' azinoksa otechestvennogo proizvodstva pri massovom lechenii v ochagakh.

Whether the Russian praziquantel analog azinox can be widely used in the foci of opisthorchiasis was first assessed. The outpatient treatment of 7405 patients with the agent in doses of 30, 40, 60 mg/kg body weight revealed that azinox tolerance did not depend upon the intensity and degree of clinical infection signs but it was slightly worse when a dose of 60 mg/kg was given. Children virtually showed no adverse reactions, in adults their frequency was no more than 52 +/- 1.4%. The parasitological efficiency of azinox in the used doses was 96-99% in children and 82-86% in adults. There was a clinical improvement in 65% of the treated. Thus, the national drug azinox is not inferior to the imported agent bilthricide in tolerance, parasitological and clinical efficiency. Bearing in mind the equal efficiency, but the better tolerance and less cost of the drug doses of 30 and 40 mg/kg body weight, it is advisable to use them in the foci for outpatient treatment.

[Efficacy and tolerance of praziquantel (Biltricide) in the treatment of distomatosis caused by Fasciola hepatica]. / Efficacité et tolérance du praziquantel (Biltricide) dans le traitement de la distomatose à Fasciola hepatica.

OBJECTIVES: Due to the side-effects of dehydroemetine, we have chosen praziquantel, a broad-spectrum antihelmintic, as a treatment for distomatosis secondary to Fasciola hepatica in humans. The aim of this retrospective study was to evaluate the efficacy and tolerance to praziquantel in patients with this disease. METHODS: Twenty-five patients (12 men) with a definite diagnosis of distomatosis and no previous treatment were followed-up between 8 months and 3 years (> 18 months in 76% of cases). The follow-up was based on clinical, biochemical and serological criteria. All patients received praziquantel (75 mg/kg/day orally) for 5 days. Treatment was started after endoscopic or surgical removal of parasites locolized in the biliary tract, in two patients. A similar therapeutic course was administered twice in four patients with persistent clinical symptoms, hypereosinophilia or arch 2 on immunoelectrophoresis. RESULTS: Cumulative rates of patients with normalized eosinophilia and seronegativation at 6, 9 and 12 months were 55, 65, 75% and 55, 70, 100%, respectively. Complete recovery occurred in 18 patients (72%) whereas hypereosinophilia persisted for more than one year in 5 patients. No side-effects, except transient nausea in a few cases, were observed. CONCLUSION: Since praziquantel seems to be both effective and well tolerated in a large proportion of patients, this drug can be recommended as a first choice for distomatosis due to Fasciola hepatica in human.