The effect of albendazole treatment on non-seizure outcomes in patients with symptomatic neurocysticercosis.
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ABSTRACT:
SUBMITTER: Thapa K
PROVIDER: S-EPMC6019022 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:To develop a causal model for the occurrence of neurocysticercosis (NC)-related seizures and test hypotheses generated from the model. METHODS:We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow-up using generalized linear mixed effect models. RESULTS:We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time-treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. SIGNIFICANCE:Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3-6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.
| S-EPMC6751555 | biostudies-literature
Project description:BACKGROUND:In neurocysticercosis, the larval form of the pork tapeworm Taenia solium appears to evolve through three phases-active, degenerative and sometimes calcification-before disappearance. The antihelmintic drug, albendazole, has been shown to hasten the resolution of active cysts in neurocysticercosis. Little is known about the time cysts take to progress through each phase, with or without treatment. METHODS:We reconfigured brain imaging data from patient level to cyst level for 117 patients in a randomized clinical trial of albendazole in which images were taken at baseline, 1, 6, 12 and 24 mo. Applying a multistate model, we modelled the hazard of a cyst evolving to subsequent cyst phases before the next imaging (vs no change). We examined the impact of albendazole treatment overall and by patient and cyst characteristics on the hazard. RESULTS:Albendazole accelerated the evolution from the active to degenerative phase (HR=2.7, 95% CI 1.3 to 6.5) and from the degenerative phase to disappearance (HR=1.9, 95% CI 1.1 to 3.9). Albendazole's impact was stronger for patients who were male, did not have calcified cysts at baseline and who had multiple cysts in different locations. CONCLUSIONS:This research provides a better understanding of where in the cyst trajectory albendazole has the greatest impact.
| S-EPMC6903786 | biostudies-literature
Project description:BACKGROUND:The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS:ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS:There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS:We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.
| S-EPMC6853673 | biostudies-literature
Project description:BackgroundThe onset of anthelmintic treatment of neurocysticercosis (NCC) provokes an acute immune response of the host, which in human cases is associated with exacerbation of neurological symptoms. This inflammation can occur at the first days of therapy. So, changes in the brain cysts appearance may be detected by medical imaging. We evaluated radiological changes in the appearance of brain cysts (enhancement and size) on days two and five after the onset of antiparasitic treatment using naturally infected pigs as a model for human NCC.Methods and resultsContrast T1-weighted magnetic resonance imaging with gadolinium was performed before and after antiparasitic treatment. Eight NCC-infected pigs were treated with praziquantel plus albendazole and euthanized two (n = 4) and five (n = 4) days after treatment; another group of four infected pigs served as untreated controls. For each lesion, gadolinium enhancement intensity (GEI) and cyst volume were measured at baseline and after antiparasitic treatment. Volume and GEI quantification ratios (post/pre-treatment measures) were used to appraise the effect of treatment. Cysts from untreated pigs showed little variations between their basal and post treatment measures. At days 2 and 5 there were significant increases in GEI ratio compared with the untreated group (1.32 and 1.47 vs 1.01, p = 0.021 and p = 0.021). Cyst volume ratios were significantly lower at days 2 and 5 compared with the untreated group (0.60 and 0.22 vs 0.95, p = 0.04 and p = 0.02). Cysts with lower cyst volume ratios showed more marked post-treatment inflammation, loss of vesicular fluid and cyst wall wrinkling.Conclusion/significanceA significant and drastic reduction of cyst size and increased pericystic enhancement occur in the initial days after antiparasitic treatment as an effect of acute perilesional immune response. These significant changes showed that early anthelmintic efficacy (day two) can be detected using magnetic resonance imaging.
| S-EPMC5470720 | biostudies-literature
Project description:BackgroundNeurocysticercosis, infection of the brain with larvae of Taenia solium (pork tapeworm), is one of several forms of human cysticercosis caused by this organism. We investigated the role of albendazole and praziquantel in the treatment of patients with parenchymal neurocysticercosis by performing a meta-analysis of comparative trials of their effectiveness and safety.Methods and principal findingsWe performed a search in the PubMed database, Cochrane Database of Controlled Trials, and in references of relevant articles. Six studies were included in the meta-analysis. Albendazole was associated with better control of seizures than praziquantel in the pooled data analysis, when the generic inverse variance method was used to combine the incidence of seizure control in the included trials (patients without seizures/[patients x years at risk]) (156 patients in 4 studies, point effect estimate [incidence rate ratio] = 4.94, 95% confidence interval 2.45-9.98). In addition, albendazole was associated with better effectiveness than praziquantel in the total disappearance of cysts (335 patients in 6 studies, random effects model, OR = 2.30, 95% CI 1.06-5.00). There was no difference between albendazole and praziquantel in reduction of cysts, proportion of patients with adverse events, and development of intracranial hypertension due to the administered therapy.ConclusionsA critical review of the available data from comparative trials suggests that albendazole is more effective than praziquantel regarding clinically important outcomes in patients with neurocysticercosis. Nevertheless, given the relative scarcity of trials, more comparative interventional studies--especially randomized controlled trials--are required to draw a safe conclusion about the best regimen for the treatment of patients with parenchymal neurocysticercosis.
| S-EPMC2265431 | biostudies-literature
Project description:PurposeAcute symptomatic seizures (ASyS) are common in critically ill patients. It is unknown how ASyS affect posthospitalization self-reported health compared to patients with established epilepsy.MethodsThis is a retrospective cohort study from 2010 to 2018. Patients were identified by an institutional epilepsy database (Ebase). Patient-reported outcome measures (PROMs) were completed as part of standard of care and included the number of seizures in the prior 4 weeks, Liverpool Seizure Severity Scale (LSSS) ictal score, quality of life in epilepsy (QOLIE)-10, Patient Health Questionnaire-9 scales, and the PROM Information System Global Health (PROMIS-GH) scale. Mixed-effects models were created to adjust for age, sex, and race and to examine score trajectory over the 1 year after baseline.ResultsA total of 15 311 established epilepsy patients and 317 patients with ASyS were identified. When compared to patients with epilepsy, patients with ASyS were older, mostly male, more often black, and had worse baseline scores on the QOLIE-10 (P < .001), PROMIS-GH Physical Health (P = .037), and LSSS Ictal (P = .006) scales. Patient-Reported Outcomes Measurement Information System Mental and Physical Health T-scores were worse than the general population (T-score = 50) for patients with both ASyS (44 and 42.5, respectively) and epilepsy (44.2 and 44.6, respectively). After adjusting for age, sex, and race, patients with ASyS reported 38% fewer seizures (P = .006) yet worse QOLIE-10 score (P = .034). We found that scores improved over time for all PROMs except for PROMIS-GH Mental Health.ConclusionCompared to patients with epilepsy, patients with ASyS had fewer seizures but worse epilepsy-specific quality of life. Independent of group status, scores generally improved over time.
| S-EPMC7271623 | biostudies-literature
Project description:BackgroundNeurocysticercosis (NCC) is a common parasitic infection of the central nervous system, caused by the tapeworm Taenia solium. It is endemic to certain parts of the world, including Central America, South America, Asia, and Africa. The racemose form, characterized by extraparenchymal location, increased morbidity and mortality, and large loculated cystic lesions, is rarely seen in industrialized countries, such as the United States. The management of racemose neurocysticercosis (RNCC) differs from that of the typical parenchymal variant. The ideal course of treatment is debated by experts, but typically includes either surgical intervention with subsequent medical therapy or medical therapy alone.Case descriptionWe present the case of a 34-year-old male diagnosed with RNCC and treated successfully with surgical cyst drainage, resection, and subsequent medical therapy.ConclusionCurrently, no standardized evidence-based protocol exists that dictate appropriate treatment for extraparenchymal or racemose NCC. We present a case of RNCC treated successfully with surgical and medical intervention. Further research encompassing well-designed clinical trials is necessary to delineate appropriate and standardized protocols for treatment of this disease.
| S-EPMC5551286 | biostudies-literature
Project description:BACKGROUND:Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. METHODS:In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. FINDINGS:Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group). INTERPRETATION:Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.
| S-EPMC4157934 | biostudies-literature
Project description:BACKGROUND:Remission criteria were proposed by Andreasen et al. for classifying patients with schizophrenia according to the severity of psychopathology. Up to the present time, there have been no cohort studies exploring the association between remission status and employment outcomes in patients with schizophrenia. The study explored whether symptomatic remission is significantly associated with employment outcomes in a two-year longitudinal study. METHODS:All 525 stable patients with schizophrenia in the therapeutic community of a public mental hospital in Taiwan were recruited between 2013 and 2015. Employment outcomes, defined as the cumulative on-the-job duration (months/per year) and income (new Taiwan dollars, NT$/per year), were investigated at the end of 1- and 2-year follow-up periods after enrollment. For repeated measurements, linear mixed models were constructed to examine the association between symptomatic remission and employment outcomes after controlling for potential confounding variables including age, sex, education, type and daily dose of antipsychotics, cognitive function, psychosocial functioning and initial employment type. RESULTS:The average age of patients was 51.8?years, and 65.3% were males. Among them, 124 patients (23.6%, 124/525) met the remission criteria at baseline. The linear mixed-model analysis showed that patients who had symptomatic remission were employed 0.8 of a month longer (p?=?0.029) and earned NT$3250 more (p?=?0.001) within 1?year than those who did not show symptomatic remission. CONCLUSION:Our study suggests that assessing symptomatic remission is a useful part of monitoring treatment effectiveness for schizophrenia, and all strategies targeting the bio-psycho-social domains to attain symptomatic remission are paramount to maintaining favorable employment outcomes.
| S-EPMC7216656 | biostudies-literature
Project description:BackgroundRespiratory syncytial virus (RSV) is an increasingly common cause of respiratory illness in adult non-immunocompromised patients. Oral ribavirin was reported to improve outcomes of RSV infection in immunocompromised patients. This study aimed to determine the outcomes of non-immunocompromised patients hospitalized with RSV-associated acute respiratory illnesses (RSV-ARI), the factors independently associated with the outcomes and the effect of oral ribavirin treatment.MethodsThis retrospective, observational cohort study included 175 adults admitted to the hospital with virologically confirmed RSV-ARI during 2014-2019. Severe ARI was identified using Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) criteria for severe community-acquired pneumonia. The primary outcome was all-cause mortality within 30 days after enrollment. A multivariable Cox model was performed to identify significant predictors of mortality.ResultsMean age was 76 ± 12.7 years. Seventy-eight (44.6%) patients met the diagnostic criteria for severe ARI. Thirty-six (20.6%) patients required invasive mechanical ventilation, and 11 (6.3%) required vasopressor. Ninety-nine (56.6%) patients received oral ribavirin treatment, and 52 (29.7%) received systemic corticosteroids. Forty-one (23.4%) patients had evidence of bacterial infection. Overall mortality was 7.4%. Mortality among patients with non-severe ARI and severe ARI was 1.04% and 15.4%, respectively. Estimated glomerular filtration rate <50 ml/min/1.73 m2 , severe ARI, systemic corticosteroids, and bacterial infection were independently associated with higher risk of mortality. Treatment with oral ribavirin was the only factor associated with reduced mortality (adjusted HR: 0.19, 95% CI: 0.04-0.9, P = 0.03).ConclusionRSV-ARI may result in significant mortality and health care utilization. Treatment with oral ribavirin may improve survival in these patients.
| S-EPMC9178057 | biostudies-literature