Using nirmatrelvir/ritonavir in patients with epilepsy: An update from the Israeli chapter of the International League Against Epilepsy.
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ABSTRACT:
SUBMITTER: Noyman I
PROVIDER: S-EPMC9314867 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Among the causes of epilepsy are several that are currently preventable. In this review, we summarize the public health burden of epilepsy arising from such causes and suggest priorities for primary epilepsy prevention. We conducted a systematic review of published epidemiologic studies of epilepsy of 4 preventable etiologic categories-perinatal insults, traumatic brain injury (TBI), central nervous system (CNS) infection, and stroke. Applying consistent criteria, we assessed the quality of each study and extracted data on measures of risk from those with adequate quality ratings, summarizing findings across studies as medians and interquartile ranges. Among higher-quality population-based studies, the median prevalence of active epilepsy across all ages was 11.1 per 1000 population in lower- and middle-income countries (LMIC) and 7.0 per 1000 in high-income countries (HIC). Perinatal brain insults were the largest attributable fraction of preventable etiologies in children, with median estimated fractions of 17% in LMIC and 15% in HIC. Stroke was the most common preventable etiology among older adults with epilepsy, both in LMIC and in HIC, accounting for half or more of all new onset cases. TBI was the attributed cause in nearly 5% of epilepsy cases in HIC and LMIC. CNS infections were a more common attributed cause in LMIC, accounting for about 5% of all epilepsy cases. Among some rural LMIC communities, the median proportion of epilepsy cases attributable to endemic neurocysticercosis was 34%. A large proportion of the overall public health burden of epilepsy is attributable to preventable causes. The attributable fraction for perinatal causes, infections, TBI, and stroke in sum reaches nearly 25% in both LMIC and HIC. Public health interventions addressing maternal and child health care, immunizations, public sanitation, brain injury prevention, and stroke prevention have the potential to significantly reduce the burden of epilepsy.
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Project description:Nirmatrelvir plus ritonavir (Paxlovid™; Pfizer) is a co-packaged combination of nirmatrelvir and ritonavir tablets, intended for co-administration and developed for the treatment and post-exposure prophylaxis of coronavirus disease 2019 (COVID-19). Nirmatrelvir is a peptidomimetic inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease, while ritonavir is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor and CYP3A inhibitor. Nirmatrelvir plus ritonavir received its first conditional authorization in December 2021 in the United Kingdom, for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19. In January 2022, nirmatrelvir plus ritonavir received authorization in the EU for use in the same indication. Nirmatrelvir plus ritonavir is authorized for emergency use in the USA. This article summarizes the milestones in the development of nirmatrelvir plus ritonavir leading to its first authorizations and approval for the treatment of COVID-19.
| S-EPMC8933659 | biostudies-literature
Project description:OBJECTIVE:Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. METHODS:This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). RESULTS:A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP. SIGNIFICANCE:This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases.
| S-EPMC6850288 | biostudies-literature
Project description:To determine the magnitude of risk factors and causes of premature mortality associated with epilepsy in low- and middle-income countries (LMICs). We conducted a systematic search of the literature reporting mortality and epilepsy in the World Bank-defined LMICs. We assessed the quality of the studies based on representativeness; ascertainment of cases, diagnosis, and mortality; and extracted data on standardized mortality ratios (SMRs) and mortality rates in people with epilepsy. We examined risk factors and causes of death. The annual mortality rate was estimated at 19.8 (range 9.7-45.1) deaths per 1,000 people with epilepsy with a weighted median SMR of 2.6 (range 1.3-7.2) among higher-quality population-based studies. Clinical cohort studies yielded 7.1 (range 1.6-25.1) deaths per 1,000 people. The weighted median SMRs were 5.0 in male and 4.5 in female patients; relatively higher SMRs within studies were measured in children and adolescents, those with symptomatic epilepsies, and those reporting less adherence to treatment. The main causes of death in people with epilepsy living in LMICs include those directly attributable to epilepsy, which yield a mean proportional mortality ratio (PMR) of 27.3% (range 5-75.5%) derived from population-based studies. These direct causes comprise status epilepticus, with reported PMRs ranging from 5 to 56.6%, and sudden unexpected death in epilepsy (SUDEP), with reported PMRs ranging from 1 to 18.9%. Important causes of mortality indirectly related to epilepsy include drowning, head injury, and burns. Epilepsy in LMICs has a significantly greater premature mortality, as in high-income countries, but in LMICs the excess mortality is more likely to be associated with causes attributable to lack of access to medical facilities such as status epilepticus, and preventable causes such as drowning, head injuries, and burns. This excess premature mortality could be substantially reduced with education about the risk of death and improved access to treatments, including AEDs.
| S-EPMC7012644 | biostudies-literature
Project description:Nirmatrelvir/Ritonavir is an oral treatment for mild to moderate COVID-19 cases with a high risk for a severe course of the disease. For this paper, a comprehensive literature review was performed, leading to a summary of currently available data on Nirmatrelvir/Ritonavir's ability to reduce the risk of progressing to a severe disease state. Herein, the focus lies on publications that include comparisons between patients receiving Nirmatrelvir/Ritonavir and a control group. The findings can be summarized as follows: Data from the time when the Delta-variant was dominant show that Nirmatrelvir/Ritonavir reduced the risk of hospitalization or death by 88.9% for unvaccinated, non-hospitalized high-risk individuals. Data from the time when the Omicron variant was dominant found decreased relative risk reductions for various vaccination statuses: between 26% and 65% for hospitalization. The presented papers that differentiate between unvaccinated and vaccinated individuals agree that unvaccinated patients benefit more from treatment with Nirmatrelvir/Ritonavir. However, when it comes to the dependency of potential on age and comorbidities, further studies are necessary. From the available data, one can conclude that Nirmatrelvir/Ritonavir cannot substitute vaccinations; however, its low manufacturing cost and easy administration make it a valuable tool in fighting COVID-19, especially for countries with low vaccination rates.
| S-EPMC10801539 | biostudies-literature
Project description:Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.
| S-EPMC7004822 | biostudies-literature
Project description: Not available
| S-EPMC9487421 | biostudies-literature
Project description:We isolated a SARS-CoV-2 BA.2 variant from a person with COVID-19 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing were performed with both parental SARS-CoV-2 and multiple variants of concern. We found that neither NM resistance nor absence of neutralizing immunity were likely causes of the recrudescence.
| S-EPMC9278181 | biostudies-literature
Project description:IntroductionAlthough real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5 days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking.MethodsThis retrospective cohort study included individuals aged ≥ 12 years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021-August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5 days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates.ResultsA total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50 years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions.ConclusionsMost patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5 days.
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Project description: Not available
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