Substandard and falsified ivermectin tablets obtained for self-medication during the COVID-19 pandemic as a source of potential harm.

In 2019, a global viral pandemic, due to the SARS-CoV-2 virus, broke out. Soon after, the search for a vaccine and/or antiviral medicine began. One of the candidate antiviral medicines tested was ivermectin. Although several health authorities warned the public against the use of this medicine outside clinical trials, the drug was widely used at the end of 2020 and in 2021. Simultaneously, several reports started to emerge demonstrating serious adverse effects after self-medicating with ivermectin. It stands to reason that the self-administration of substandard or falsified (SF) medicines bearing harmful quality deficiencies have contributed to this phenomenon. In order to have a better view on the nature of these harmful quality deficiencies, SF ivermectin samples, intercepted in large quantities by the Belgian regulatory agencies during the period 2021-2022, were analyzed in our official medicines control laboratory. None of the samples (n = 19) were compliant to the quality criteria applicable to medicinal products. These SF products either suffered from a systematic underdosing of the active pharmaceutical ingredient or were severely contaminated with bacteria, two of which were contaminated with known pathogens that cause gastrointestinal illness upon oral intake. In addition to the direct risks of self-medicating with such a product, the improper usage and dosage of ivermectin medication might also facilitate ivermectin tolerance or resistance in parasites. This may have detrimental consequences on a global scale, certainly as the number of newly developed active pharmaceutical ingredients that can safely be used to combat parasites is rather scarce.

Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial.

BACKGROUND: In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown. METHODS: In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding. RESULTS: Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; P=0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; P=0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compared with the VKA group was 0.39 (95% CI, 0.17 to 0.90; P=0.03) in the rivaroxaban group, 0.48 (95% CI, 0.22 to 1.08; P=0.08) in the rivaroxaban and vitamin K2 group and 0.44 (95% CI, 0.23 to 0.85; P=0.02) in the pooled rivaroxaban groups. CONCLUSIONS: In patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Oral Anticoagulation in Hemodialysis, NCT03799822.

Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The use of vitamin K antagonists (VKAs) in hemodialysis patients with atrial fibrillation (AF) is controversial. No randomized trials are available and observational studies have yielded conflicting results, engendering a large clinical practice variability and physician uncertainty. An unresolved but highly relevant question is whether AF poses a true risk of ischemic stroke in hemodialysis and whether any form of oral anticoagulation is therefore warranted. METHODS: We conducted a systematic review of studies that compared the incidence of ischemic stroke and bleeding in hemodialysis patients with AF taking VKA and those not taking VKA. When hemodialysis patients had been pooled with peritoneal dialysis, kidney transplant, or stage V chronic kidney disease patients, unpublished outcome data of the hemodialysis subgroup were obtained through personal communication. The main outcome measures were ischemic stroke/thromboembolic events, all-cause mortality, major bleeding, and hemorrhagic stroke. Combined hazard ratios (HRs) and 95% CIs were calculated using a random-effects model. RESULTS: Twelve prospective or retrospective cohort studies were included in the meta-analysis, totaling 17,380 hemodialysis patients of whom 4,010 (23.1%) received VKA. In VKA-treated patients, mean CHADS2 or CHA2DS2VASc score was low (range 1.7-2.75) or a sizeable proportion of patients had scores <2 (range 2%-23%). Time in the therapeutic range or mean international normalized ratio was generally low. Treatment with VKA was associated with a nonsignificant 26% reduction of the risk of ischemic stroke (HR 0.74; 0.51-1.06), a 21% increase in total bleeding risk (HR 1.21; 1.03-1.43), and no effect on mortality (HR 1.00; 0.92-1.09). Vitamin K antagonist almost doubled the risk of hemorrhagic stroke, but this did not reach the limit of statistical significance (4 studies, n = 16.365; HR 1.93; 0.93-3.98). CONCLUSION: Our meta-analysis revealed a trend for a reduction of the risk of ischemic stroke in hemodialysis patients with AF treated with VKA. The true protective effect may have been underestimated, owing to inclusion of low-risk patients not expected to benefit from anticoagulation and to suboptimal anticoagulation. However, assessment of the overall effect of VKA in hemodialysis patients should also take into account the increased risk of bleeding, in particular of hemorrhagic stroke. Whether new oral anticoagulants provide a better benefit-risk ratio in hemodialysis patients should be the subject of future trials.

Gouty arthritis of the spine in a renal transplant patient: a clinical case report: an unusual presentation of a common disorder.

Axial gout is a well-documented but uncommon manifestation of gout. Its mimicking nature and the impracticality of axial joint aspiration might considerably delay its diagnosis. We report a case in a normouricemic renal transplant recipient, whereby the primary symptom of severe neck pain suggested pyogenic spondylodiscitis as an initial tentative diagnosis. Clinical findings included a high C-reactive protein concentration and elevated body temperature. The patient did not respond to empiric antibiotic treatment and suffered consecutive attacks of severe wrist and ankle pain in conjunction with a persistent fever. Blood and joint cultures were negative, but analysis of aspirated ankle joint fluid revealed monosodium urate crystals. A dual-energy computed tomography scan confirmed the presence of monosodium urate crystals in the costovertebral joints. Colchicine treatment dramatically improved the patient's clinical condition. Axial gout should be considered in transplant recipients with severe neck or back pain, fever, and increased inflammatory parameters with a high likelihood of an infectious etiology, despite the presence of paradoxically normal or even decreased serum urate concentrations. Dual-energy computed tomography is a noninvasive technique of possible benefit in the detection of axial gout when joint fluid aspiration is not deemed safe.

Hemodialysis catheter design and catheter performance: a randomized controlled trial.

BACKGROUND: A complication of long-term use of tunneled cuffed catheters for hemodialysis is the high rate of infection and thrombus-related dysfunction. Specific mechanical features of tunneled cuffed catheters may improve hemodynamic performance and decrease thrombosis and infection rates. However, there currently is no proven advantage of one design over another. STUDY DESIGN: Single-center randomized clinical trial. SETTING & PARTICIPANTS: 302 hemodialysis patients who required a tunneled cuffed catheter as temporary or definite vascular access. INTERVENTION: Palindrome Symmetric Tip Dialysis Catheter or HemoStar Long-Term Hemodialysis Catheter. OUTCOMES & MEASUREMENTS: The primary end point was primary assisted patency. Secondary end points were incidence of catheter-related bloodstream infections (CRBSIs), thrombosis, and 2 indicators of rheologic function: mean effective blood flow rate and urokinase use. RESULTS: Mean primary assisted patency was 135.9 days for Palindrome and 136.5 days for HemoStar (P=0.8). Definite CRBSI occurred in 0.24 and 0.10/1,000 catheter-days for Palindrome and HemoStar, respectively (P=0.3). Removal rates for thrombosis that could not be resolved with thrombolysis were 0.53 and 0.43/1,000 catheter-days for Palindrome and HemoStar, respectively (P=0.7). Urokinase use was lower for Palindrome than for HemoStar, as evidenced by a lower number of urokinase infusions/1,000 catheter-days (17 and 35; P<0.001) and higher number of catheters that never required thrombolysis (58% and 45%; P=0.03). Mean effective blood flow rate was higher for Palindrome than for HemoStar (333 and 304mL/min; P<0.001). LIMITATIONS: Single-center nonblinded trial. CONCLUSIONS: Primary assisted patency and incidence of infection and thrombosis were similar for both catheter types. The Palindrome catheter required less thrombolysis and achieved higher blood flow rates than the HemoStar catheter. These findings suggest that mechanical catheter design may improve catheter rheology, but does not affect risks for thrombosis and infection and hence catheter survival.