Towards malaria elimination: a case-control study to assess associated factors to malaria relapses in the extra-Amazon Region of Brazil from 2008 to 2019.

BACKGROUND: Malaria is an infectious disease caused by the Plasmodium species and is a global burden. When not treated correctly, it can reemerge as a relapse or recrudescence. Malaria relapse cases can contribute to maintaining active transmission chains and can influence the patient to develop severe malaria, potentially leading to hospitalization or death. The objective of this study is to estimate the number of malaria relapse cases in the extra-Amazon region of Brazil and to investigate the associated factors. METHODS: This is a case-control study that analyses malaria infections caused by Plasmodium vivax, as reported in Notifiable Diseases Information System (Sinan) for the Brazilian extra-Amazon region (an area not endemic for the disease) from 2008 to 2019. For the identification of relapse cases, deduplication record linkage processes in R software were used. Malaria relapses were defined as the case group, and new malaria infections were defined as the control group. Logistic regression models were used to assess associated factors. RESULTS: Of the 711 malaria relapses, 589 (82.8%) were first relapses. Most relapses (71.6%) occurred between 30 and 120 days after the previous infection. Malaria relapses are spread throughout the extra-Amazon region, with a higher concentration near big cities. Driver occupation was found to be a common risk factor compared to other occupations, along with asymptomatic individuals. Other associated factors were: being infected in the Brazilian Amazon region, having follow-ups for malaria relapses, and having parasite density of the previous infection higher than 10,000 parasites per mm3. CONCLUSIONS: This study provides evidence that allows malaria health surveillance services to direct their efforts to monitor cases of malaria in the highest risk segments identified in this study, particularly in the period between 30 and 120 days after being infected and treated. Relapses were associated to driver occupation, absence of symptoms, infection in endemic areas of Brazil, being detected through active surveillance or routine follow-up actions, and with parasitaemia greater than 10,000 parasites per mm3 in the previous infection. Improving cases follow-up is essential for preventing relapses.

Epidemiology and management of transient ischemic attack in Trieste district, how day hospital assessment improves outcomes: a five-year retrospective study.

BACKGROUND: Transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction, without acute infarction or tissue injury lasting less than 24 h. Previous data suggest TIA precedes 15% of ischemic strokes, with a higher risk in the first week. Current practice guidelines advise evaluation through rapid neurological visit or admission to hospital. We provide data on TIA incidence in Trieste, and we compare three different types of assessment: day hospital (DH), stroke unit (SU), and emergency department/outpatients (ED). METHODS: This is a 5-year retrospective study of transient cerebrovascular events admitted in the University Hospital of Trieste (230.623 inhabitants), between 2016 and 2020. We calculated TIA prevalence in Trieste district's general population. Our primary endpoint is ischemic recurrences within 90 days, and we evaluate the possible association between different types of management. RESULTS: TIA incidence rate was 0.54/1000 inhabitants. In the multivariate analysis remained significantly associated with primary endpoint: ABCD2 (OR 1.625, CI 95% 1.114-2.369, p = 0.012) and DH evaluation (OR 0.260, CI 95% 0.082-0.819, p = 0.021). CONCLUSIONS: Incidence of TIA in Trieste district is in line with previous data. We demonstrate the crucial role of DH evaluation over the outpatient/ED in reducing overall mortality and recurrence rate. Prompt recognition of patients at high risk for cerebrovascular events and specialist follow-up may reduce the incidence of major vascular events and death.

A Self-Reported Study on Explanatory Variables of Stress in Multiple Sclerosis Patients: Exploring the Effect of Physical Conditions and Emotion Regulation Processes.

BACKGROUND: Multiple sclerosis (MS)-linked stress is frequent, multidetermined and facilitates the onset/exacerbation of MS. However, few explanatory models of stress analysed the joint explanatory effect of emotion regulation and clinical outcomes of MS in those patients. OBJECTIVE: This study explored whether self-reported MS-related conditions (number of relapses, fatigue and global disability) and specific emotion regulation processes (experiential avoidance and self-compassion) explain stress symptoms in MS patients. METHODS: The MS sample comprised 101 patients with MS diagnosis receiving treatment in hospitals and recruited through the Portuguese MS Society. The no-MS sample included 134 age-, sex- and years of education-matched adults without MS recruited from the general Portuguese population. Both samples did not report other neurological disorders. Data were collected using self-response measures. RESULTS: All potential explanatory variables differed significantly between samples, with higher scores found in MS patients. In MS clinical sample, those variables and years of education correlated with stress symptoms and predicted stress symptoms in simple linear regression models. These results allowed their selection as covariates in a multiple linear regression model. Years of education, the number of relapses, fatigue and experiential avoidance significantly predicted 51% of stress symptoms' total variance. CONCLUSIONS: This study provides preliminary evidence on the importance of clinicians and researchers considering the simultaneous contribution of years of education, the number of perceived relapses, fatigue and experiential avoidance as factors that can increase vulnerability to stress in MS patients. Psychological intervention programmes that tackle these factors and associated stress symptomatology should be implemented.

Genetic Profiling of Plasmodium ovale wallikeri Relapses With Microsatellite Markers and Whole-Genome Sequencing.

Like Plasmodium vivax, both Plasmodium ovale curtisi and Plasmodium ovale wallikeri have the ability to cause relapse in humans, defined as recurring asexual parasitemia originating from liver-dormant forms subsequent to a primary infection. Here, we investigated relapse patterns in P ovale wallikeri infections from a cohort of travelers who were exposed to the parasite in sub-Saharan Africa and then experienced relapses after their return to France. Using a novel set of 8 highly polymorphic microsatellite markers, we genotyped 15 P ovale wallikeri relapses. For most relapses, the paired primary and relapse infections were highly genetically related (with 12 being homologous), an observation that was confirmed by whole-genome sequencing for the 4 relapses we further studied. This is, to our knowledge, the first genetic evidence of relapses in P ovale spp.

Detecting isolated cognitive relapses in persons with MS.

BACKGROUND: The existence of isolated cognitive relapses (ICRs) in persons with MS (PwMS) has been debated. OBJECTIVE: To examine relapses with decline on Symbol Digit Modalities Test (SDMT) but no change on Expanded Disability Status Scale (EDSS). METHODS: This 3-year prospective cohort study identified PwMS experiencing a relapse with decrease on SDMT. Participants with SDMT decline/stable EDSS were labeled "ICR," while those with a corresponding decrease on EDSS were classified "Relapse with Cognitive Decline (RCD)." Two definitions of SDMT decline were explored: (1) ⩾ 8 points, and (2) ⩾ 4 points. Logistic regression was used to analyze the relationship between ICR and RCD. RESULTS: The full cohort had 592 participants: 83 experienced relapses; 22 (26.5%) had an SDMT decrease of ⩾ 8 points; 14 (63.6%) met ICR criteria. Logistic regression (X2(1) = 5.112, p = 0.024) using demographics and disease characteristics explained 28.4% of the variance in ICR versus RCD. Only the MS Neuropsychological Questionnaire was associated with ICR (odds ratio (OR): 8.6; 95% confidence interval (CI): 1.1-16.4) 40 relapsing participants with SDMT decrease of ⩾ 4 points were identified: 26 (65%) had a stable EDSS (ICR). Logistic regression did not find any variable predictive of ICR. CONCLUSION: This prospective study demonstrates evidence of ICR in PwMS.

Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community.

BACKGROUND AND OBJECTIVES: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. METHODS: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. RESULTS: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. CONCLUSION: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles.

Frequency of new asymptomatic MRI lesions during attacks and follow-up of patients with NMOSD in a real-world setting.

BACKGROUND: We aimed to assess the frequency of new asymptomatic lesions on brain and spinal imaging (magnetic resonance imaging (MRI)) and their association with subsequent relapses in a large cohort of neuromyelitis optica spectrum disorder (NMOSD) patients in Argentina. METHODS: We retrospectively reviewed 675 MRI (225 performed during an attack and 450 during the relapse-free period (performed at least 3 months from the last attack)) of NMOSD patients who had at least 2 years of clinical and MRI follow-up since disease onset. Kaplan-Meier (KM) curves were used for depicting time from remission MRI to subsequent relapse. RESULTS: We included 135 NMOSD patients (64.4% were aquaporin-4-immunoglobulin G (AQP4-IgG)-positive). We found that 26 (19.26%) and 66 (48.88%) of patients experienced at least one new asymptomatic MRI lesion during both the relapse-free period and attacks, respectively. The most frequent asymptomatic MRI lesions were optic nerves followed by short-segment myelitis during the relapse-free period and attacks. KM curves did not show differences in the time taken to develop a new relapse. CONCLUSION: Our findings showed that new asymptomatic lesions are relatively frequent. However, the presence of new asymptomatic MRI lesions during the relapse-free period and at relapses was not associated with a shorter time to developing subsequent relapses.

Systemic relapses of primary CNS lymphomas (PCNSL): a LOC network study.

Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms.

Efficacy and safety of co-trimoxazole in eradication phase of melioidosis; systematic review.

BACKGROUND: Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis. The safety profile of co-trimoxazole was not documented in the literature, nor have systematic studies of its effectiveness been done. This systematic review sought to study on the dose, duration and combination of co-trimoxazole therapy in view of clinical efficacy and safety in the eradication phase of melioidosis. MAIN BODY: This systematic review included all of the published articles that employed co-trimoxazole in the eradication phase after 1989, including, randomized clinical trials, case-control studies, cohorts, case reports, and case series. Throughout the eradication (maintenance) phase, co-trimoxazole usage was permissible in any dose for any period. A total of 40 results were included in the analysis which contained six clinical trials, one cohort study, one Cochrane review, and thirty-two case series/case reports. Clinical and microbial relapse rates are low when co-trimoxazole is used in single therapy than in combination. There were several adverse events of co-trimoxazole, however, a quantitative analysis was not conducted as the data did not include quantitative values in most studies. SHORT CONCLUSION: The dose of co-trimoxazole, duration of the eradication phase, and other combinations used in the treatment was varying between studies. Compared to combined therapy patients treated with co-trimoxazole alone the mortality and relapse rates were low. The lowest relapse rate and lowest mortality rate occur when using co-trimoxazole 1920 mg twice daily. The duration of therapy varies on the focus of melioidosis and it is ranged from 2 months to one year and minimum treatment duration associated with low relapse rate is 3 months. The use of co-trimoxazole over the maintenance phase of melioidosis is associated with clinical cure but has adverse effects.

Single vs split dose of prednisolone in the treatment of relapses of childhood nephrotic syndrome.

Nephrotic syndrome is the commonest glomerular disease in childhood. It usually follows a relapsing and remitting course. Corticosteroids are the mainstay of treatment for both the first episode and subsequent relapses. This study was conducted at a single centre to compare the clinical response to a single dose vs. split dose of prednisolone in the treatment of relapses of childhood nephrotic syndrome. Children between the ages of 1 and 14 years admitted with a relapse of idiopathic steroid sensitive nephrotic syndrome from August 2019 to February 2020 were considered for recruitment. A block randomization method based on age was used for allocation. Patients randomised to group A received oral prednisolone at 60 mg/m2 as a single morning dose, while those randomised to group B received the same total dose as two divided doses, of which 2/3 was given in the morning and the rest in the evening. Treatment was continued until remission was achieved following which all patients were switched to alternate day prednisolone. An independent sample t test was used to compare the two groups. One hundred and four episodes of relapse occurring in 96 children were included of which 49 were treated with prednisolone as a split dose and 55 were treated with a single dose of prednisolone. The mean duration to achieve remission for the split-dose group was 8.02 days (SD 1.58) while it was 9.74 days (SD 3.72) for the single-dose group. This difference was statistically highly significant (t(102) = 3.004; p = 0.001; CI 0.58 to 2.86). There was no difference in the adverse events profile of the two groups.  Conclusion: The use of prednisolone as a split dose results in a shorter duration to achieve remission when compared to a single morning dose, resulting in a lower cumulative dose of prednisolone to achieve remission. What is Known: • Corticosteroids are the mainstay of treatment for childhood nephrotic syndrome. • Corticosteroids are given as a single dose in the morning to minimise adrenocortical suppression. What is New: • A more rapid attainment of remission can be achieved with a split dose of corticosteroids.

Brain MRI activity during the year before pregnancy can predict long-term clinical worsening in patients with Multiple Sclerosis.

BACKGROUND: Pregnancy has been observed to reduce the frequency of relapses in Multiple Sclerosis (MS) patients, but the relapse risk tends to increase during the early post-partum period. Increased pre- and post-partum disease activity may predict a poor long-term prognosis. This study aimed to evaluate the correlation between magnetic resonance imaging (MRI) activity during the year before pregnancy and long-term clinically meaningful worsening in Expanded Disability Status Scale (EDSS). METHODS: This observational, retrospective, case-control study included 141 pregnancies in 99 females with MS. Statistical analyses were used to evaluate the correlation between MRI activity during the year pre-pregnancy and post-partum clinical worsening during a 5-year follow-up. Clustered logistic regression was used to investigate the predictors of 5-year clinically meaningful worsening in EDSS (lt-EDSS). RESULTS: We found a significant correlation between an active MRI pre-pregnancy and lt-EDSS (p = 0.0006). EDSS pre-pregnancy and lt-EDSS were also significantly correlated (p = 0.043). Using a multivariate model, we predicted which females would not experience long-term clinical deterioration by a stable MRI pre-pregnancy (92.7% specificity; p = 0.004). CONCLUSIONS: An active MRI pre-conception is a strong predictor of lt-EDSS and a higher annual relapse rate during the follow-up period, regardless of whether the female had clinical evidence of disease activity prior to conception and delivery. Optimizing disease control and achieving imaging stability prior to conception may reduce the risk of long-term clinical deterioration.

The course of non-infectious uveitis in pregnancy: a retrospective study of 79 pregnancies.

PURPOSE: The study aims to describe the course and management of non-infectious uveitis during pregnancy and postpartum period in European populations. METHODS: A retrospective observational study in two tertiary centers in France was performed. Pregnant patients during the follow-up of a non-infectious uveitis as well as those with new-onset uveitis were included. The medical records were analyzed with a systematic collection of the characteristics of the uveitis, the treatment and evolution of the uveitis, and the course of the pregnancy including obstetric complications. RESULTS: Seventy-nine pregnancies in 59 women were included: 48 patients (68 pregnancies) were followed for uveitis and 11 had a new-onset uveitis diagnosis. Most patients had idiopathic uveitis (32.2%) or sarcoid uveitis (27.1%). Among the patients followed for uveitis at the time of conception, there were 18 relapses (26.5%) requiring treatment escalation. Relapses occurred mainly in the two first trimester (n = 12) or during the postpartum period (n = 5) and were significantly associated with an active uveitis at the time of conception (OR = 9.2, 95% CI [1.57-48.4], p = 0.01). The characteristics of the new-onset uveitis were similar to those already existing before pregnancy. Obstetric complications occurred in 25 pregnancies (31.6%), mainly gestational hypertension and gestational diabetes. CONCLUSION: The frequency of non-infectious uveitis relapses decreases as pregnancy progresses, in agreement with data from other non-European studies. However, multidisciplinary monitoring should be advised, especially to uncontrolled patients at the time of conception.

Diagnostic accuracy of antineutrophil cytoplasmic antibodies (ANCA) in predicting relapses of ANCA-associated vasculitis: systematic review and meta-analysis.

Relapse in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is associated with significant morbidity and mortality. Utility of ANCA for prediction of relapses is still controversial. PubMed/MEDLINE, Scopus, and WebOfScience were searched, screened and confirmed for inclusion [PROSPERO No: CRD42020220308]. Studies measuring serial ANCA by ELISA or indirect immunofluorescence (IF), reporting relapses with sufficient data to calculate sensitivity and specificity were included. Diagnostic odds ratio (OR), sensitivity, specificity and likelihood ratios (LR) were synthesized using a bivariate mixed-effect regression model. Sub-group analysis included a comparison between ELISA and IIF, anti-myeloperoxidase (MPO) and -proteinase 3(PR3), and type of rise in ANCA. For meta-analysis of survival outcomes, hazard ratios were synthesized using a random-effect model. QUADAS-2 was used for assessing quality of studies, I2 statistic for heterogeneity Begg's test for publication bias. 2946 abstracts and 43 full-texts were reviewed to identify 26 eligible studies that included 2623 patients with AAV and 848 relapses. Overall heterogeneity was high [I2 = 99%] and the overall risk of bias was low to moderate. ANCA positivity by either ELISA or immunofluorescence for predicting relapse of AAV had a sensitivity of 0.70(95% CI 0.58-0.81), specificity of 0.66(0.55-0.76), positive LR of 2.1(1.6-42.7) and negative LR of 0.44(0.30-0.60). ELISA performed marginally better [OR: 5(3-7)] than IIF [OR: 4(2-9)] with similar sensitivity, specificity, PLR and NLR. The area under the curve for PR3 was 0.74(0.7-0.77), while that for MPO was not computed as the number of eligible studies was only three. In the survival analysis, the hazard ratio for relapse was 3.11(1.7-5.65). The meta-analysis shows modest accuracy of ANCA in predicting relapses of ANCA vasculitis and supports the use of serial ANCA monitoring as a biomarker for relapse.

Treatment regimens for neuromyelitis optica spectrum disorder attacks: a retrospective cohort study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy. METHODS: We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome. RESULTS: We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response. CONCLUSIONS: We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids.

Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies.

BACKGROUND: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study of patients with relapsing-remitting multiple sclerosis, treatment with cladribine tablets 3.5 mg/kg (CladT) significantly reduced the annualised relapse rate (ARR) versus placebo; this effect was sustained in CLARITY Extension, without further treatment. OBJECTIVE: To assess the frequency and severity of relapses in patients treated with CladT versus placebo in CLARITY over 2 years and evaluate the durability of effect in patients who received no further treatment for 2 years in CLARITY Extension. METHODS: In this post hoc analysis, ARRs were calculated for qualifying and all relapses, and qualifying and all severe relapses (i.e. requiring steroid treatment or leading to hospitalisation) in patients treated with CladT (n = 433) and placebo (n = 437) in CLARITY, and those from the CladT group who received placebo in CLARITY Extension (n = 98). RESULTS: At Month 6, Year 1 and Year 2, patients receiving CladT had a significantly lower risk of qualifying or all relapses (all p < 0.0001), and qualifying or all severe relapses (all p < 0.005), compared with placebo. This effect was sustained in CLARITY Extension without further treatment. CONCLUSION: The results show durable efficacy of cladribine tablets 3.5 mg/kg for reducing frequency and severity of relapses in patients with relapsing-remitting multiple sclerosis.CLARITY: NCT00213135; CLARITY Extension: NCT00641537.

Factors involved in time reduction between seizure relapses in patients with epilepsy attending emergency rooms in Medellín, Colombia.

BACKGROUND: Seizure relapses are the leading cause of admission to emergency rooms (ER) in people with epilepsy. OBJECTIVE: To analyze administrative and clinical factors associated with the duration between seizure relapses in people with epilepsy admitted to the Neurological Institute of Colombia (Medellin) between July 2018 and July 2019. MATERIALS AND METHODS: A retrospective follow-up study of 156 patients over 18 years old, diagnosed with epilepsy, and treated for over a year. The outcome variable was the time between seizure relapses, identified through the record of ER attendances. In addition, difficulties in the prescription filling process (delay, omission, or brand change) and clinical characteristics were analyzed as potential associated influence factors. The statistical analysis was performed using the Prentice, Williams & Peterson-Gap Time survival model for recurrent events. Finally, Adjusted Hazard Ratios (aHR) with 95% confidence intervals (95%CI) are also presented. RESULTS: One hundred fifty-six patients were analyzed. Their average age of diagnosis was 15.5 years (SD = 22.5), the median number of monthly seizures was 3 (SD = 9.3), and 50.6% were women. Moreover, difficulties in the prescription filling process were associated with a time reduction between seizure relapses (aHR = 2.61; 95%CI 1.49-4.57), showing a similar impact as having a history of three or four types of events (aHR = 2.96; 95%CI 1.23-7.12) and neuropsychiatric comorbidity (aHR = 1.89; 95%CI 1.04-3.54). CONCLUSION: Neuropsychiatric comorbidity, history of several types of events, and experiencing difficulties with prescription filling are associated with lower benefit from treatment to control seizure relapses.

Mild blurry vision as the initial presentation of central nervous system relapses of acute lymphoblastic leukemia: a case report.

BACKGROUND: Leukemia relapses after hematopoietic stem cell transplantation can sometimes occur from the central nervous system prior to relapse from the bone marrow, and manifestations varied. CASE REPORT: We present a case of mild blurry vision as the initial symptom of central nervous system relapse of adult acute lymphoblastic leukemia. A 30-year-old man presented with a 1 week history of painless visual loss in both eyes. At that time there were no headaches or other systemic features. The neurological examination was without positive findings except bilateral optic nerve edema. He had a history of acute lymphoblastic leukemia and hematopoietic stem cell transplantation, which had been in clinical remission post-transplant for 1 year. Lumbar puncture revealed relapsed disease within the central nervous system, confirmed with cerebrospinal fluid leukemic blasts. CONCLUSIONS: It highlights the need for ophthalmologists to be aware of the possibility of central nervous system involvement in patients with the setting of leukemia when visual symptoms as the initial manifestation.

Molecular diagnosis and therapy for Plasmodium ovale infection of a returned traveler from East Africa.

Malaria is an infectious disease caused by Plasmodium parasites that are mainly transmitted through the bites of infected female Anopheles mosquitoes. The average annual number of malaria cases was less than ten in Taiwan in the last five years. Most of the cases were caused by Plasmodium vivax and Plasmodium falciparum, and were primarily diagnosed in travelers who returned from Southeast Asia and Africa. Here, we report the first case of Plasmodium ovale infection within five years that was confirmed by peripheral blood smear examination and molecular identification in a 25-year-old Asian female patient who returned from Uganda.

A randomized study of natalizumab dosing regimens for relapsing-remitting multiple sclerosis.

BACKGROUND: REFINE was an exploratory, dose- and frequency-blinded, prospective, randomized, dose-ranging study in relapsing-remitting multiple sclerosis (RRMS) patients. OBJECTIVE: To examine the efficacy, safety, and tolerability of natalizumab administered via various regimens in RRMS patients. METHODS: Clinically stable RRMS patients previously treated with 300 mg natalizumab intravenously for ⩾12 months were randomized to one of six natalizumab regimens over 60 weeks: 300 mg administered intravenously or subcutaneously every 4 weeks (Q4W), 300 mg intravenously or subcutaneously every 12 weeks (Q12W), or 150 mg intravenously or subcutaneously Q12W. The primary endpoint was the mean cumulative number of combined unique active magnetic resonance imaging (MRI) lesions at week 60. RESULTS: In total, 290 patients were enrolled. All Q12W dosing arms were associated with increased clinical and MRI disease activity and closed early; ⩾39.5% of patients in each Q12W arm met rescue criteria. In the 300 mg intravenous and subcutaneous Q4 W arms, the mean cumulative number of combined unique active MRI lesions was 0.23 and 0.02, respectively; annualized relapse rates were 0.07 and 0.08, respectively; and trough natalizumab serum levels and α4-integrin saturation were comparable. CONCLUSION: Natalizumab 300 mg subcutaneous Q4W was comparable to 300 mg intravenous Q4W dosing with respect to efficacy, pharmacokinetics/pharmacodynamics, and safety.

Siponimod: Disentangling disability and relapses in secondary progressive multiple sclerosis.

BACKGROUND: In multiple sclerosis, impact of treatment on disability progression can be confounded if treatment also reduces relapses. OBJECTIVE: To distinguish siponimod's direct effects on disability progression from those on relapses in the EXPAND phase 3 trial. METHODS: Three estimands, one based on principal stratum and two on hypothetical scenarios (no relapses, or equal relapses in both treatment arms), were defined to determine the extent to which siponimod's effects on 3- and 6-month confirmed disability progression were independent of on-study relapses. RESULTS: Principal stratum analysis estimated that siponimod reduced the risk of 3- and 6-month confirmed disability progression by 14%-20% and 29%-33%, respectively, compared with placebo in non-relapsing patients. In the hypothetical scenarios, risk reductions independent of relapses were 14%-18% and 23% for 3- and 6-month confirmed disability progression, respectively. CONCLUSION: By controlling the confounding impact of on-study relapses on confirmed disability progression, these statistical approaches provide a methodological framework to assess treatment effects on disability progression in relapsing and non-relapsing patients. The analyses support that siponimod may be useful for treating secondary progressive multiple sclerosis in patients with or without relapses.