Attitudes, practices, and determinants of community care-seeking behaviours for fever/malaria episodes in the context of the implementation of multiple first-line therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso.

BACKGROUND: Malaria case management relies on World Health Organization (WHO)-recommended artemisinin-based combination therapy (ACT), and a continuous understanding of local community knowledge, attitudes, and practices may be a great support for the success of malaria disease control efforts. In this context, this study aimed to identify potential facilitators or barriers at the community level to inform a health district-wide implementation of multiple first-line therapies (MFT) as a new strategy for uncomplicated malaria case management. METHODS: A community-based cross-sectional study using a mixed-method design was carried out from November 2018 to February 2019, in the health district (HD) of Kaya in Burkina Faso. Quantitative data were collected using a standardized questionnaire from 1394 individuals who had fever/malaria episodes four weeks prior to the survey. In addition, 23 focus group discussions (FGDs) were conducted targeting various segments of the community. Logistic regression models were used to assess the predictors of community care-seeking behaviours. RESULTS: Overall, 98% (1366/1394) of study participants sought advice or treatment, and 66.5% did so within 24 h of fever onset. 76.4% of participants preferred to seek treatment from health centres as the first recourse to care, 5.8% were treated at home with remaining drug stock, and 2.3% preferred traditional healers. Artemether-lumefantrine (AL) was by far the most used anti-malarial drug (98.2%); reported adherence to the 3-day treatment regimen was 84.3%. Multivariate analysis identified less than 5 km distance travelled for care (AOR = 2.7; 95% CI 2.1-3.7) and education/schooling (AOR = 1.8; 95% CI 1.3-2.5) as determinants of prompt care-seeking for fever. Geographical proximity (AOR = 1.5, 95% CI 1.2-2.1), having a child under five (AOR = 4.6, 95% CI 3.2-6.7), being pregnant (AOR = 6.5, 95% CI 1.9-22.5), and living in an urban area (AOR = 2.8, 95% CI 1.8-4.2) were significant predictors for visiting health centres. The FGDs showed that participants had good knowledge about malaria symptoms, prevention tools, and effective treatment. Behaviour change regarding malaria treatment and free medication for children under five were the main reasons for participants to seek care at health centres. CONCLUSIONS: The study showed appropriate knowledge about malaria and positive community care-seeking behaviour at health centres for fever/malaria episodes. This could potentially facilitate the implementation of a MFT pilot programme in the district. CLINICALTRIALS: gov Identifier: NCT04265573.

A snapshot on patient-reported outcome measures of people with multiple sclerosis on first-line therapies in a real world setting.

BACKGROUND: Patient-reported outcomes (PROs) may help patients and clinicians in selecting disease-modifying therapies (DMTs) for multiple sclerosis (MS). OBJECTIVE: To evaluate PRO differences among first-line DMTs for relapsing-remitting (RR) people with MS (pwMS). METHODS: Multicenter study. RR pwMS on first-line DMTs completed Fatigue Severity Scale (FSS), PROs Indices for MS (PRIMUS), 36-item Short-Form Health Survey (SF-36), treatment satisfaction questionnaire for medication (TSQM), Beck Depression Inventory-II (BDI-II), and Symbol Digit Modalities Test (SDMT). Differences among PROs across DMTs were tested by ANOVA. Multivariable linear regressions were used to investigate associations between PROs and the treatment group. RESULTS: Two-hundred eighty pwMS were enrolled: 56% were on interferons (INF), 22% on dimethylfumarate (DMF), 13% on glatiramer acetate, and 9% on teriflunomide (Teri). Compared with INF, pwMS on Teri were the oldest, with higher disability, worst depression at BDI, worst cognitive performances at SDMT (p = 0.001), fatigue at FSS (p = 0.001), and activity limitation and quality of life respectively at PRIMUS (p = 0.005) and SF-36 Mental Composite Score (p < 0.001); pwMS on DMF reported highest side effects and, together with pwMS on Teri, better treatment satisfaction at TSQM. CONCLUSIONS: Compared with INF-treated patients, pwMS on DMF and Teri reported the best treatment satisfaction, although DMF-treated pwMS reported higher side effects and those on Teri the worst QoL and fatigue; however, the older age, higher disability and depression, and worse cognitive performance of pwMS on Teri suggest to be careful in evaluating these results.

Comparisons of Therapeutic Efficacy and Safety of Solifenacin versus Tolterodine in Patients with Overactive Bladder: A Meta-Analysis.

OBJECTIVES: This meta-analysis was to assess solifenacin and tolterodine in patients with overactive bladder. METHODS: We searched PubMed, the Cochrane Library, EMBASE, CNKI, Wanfang, and ClinicalTrials.gov databases for randomized controlled trials (RCTs). The efficacy endpoint was daily micturition frequency, daily urgency episodes, daily incontinence episodes, and micturition volume per voiding. The safety endpoint was the incidence of the rate of major bleeding, intracranial bleeding, and gastrointestinal bleeding. RESULTS: Seven RCTs met the inclusion criteria and 1,318 patients were included. The meta-analysis showed that, compared with tolterodine, solifenacin was associated with similar daily micturition frequency, daily urgency episodes, daily incontinence episode, and micturition volume per voiding at 8 and 12 weeks of follow-up. Moreover, no significant difference was obtained in the incidence of dry mouth between solifenacin and tolterodine at 8 and 12 weeks of follow-up. However, tolterodine decreased the constipation rate at 12 weeks compared with solifenacin. CONCLUSION: Solifenacin and tolterodine yielded similar results on daily micturition frequency, daily urgency episodes, daily incontinence episodes, micturition volume per voiding, and the incidence of dry mouth. However, tolterodine can decrease the constipation rate at 12 weeks compared with solifenacin.

Feasibility and Acceptability of a Strategy Deploying Multiple First-Line Artemisinin-Based Combination Therapies for Uncomplicated Malaria in the Health District of Kaya, Burkina Faso.

(1) Background: Effective malaria case management relies on World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs), but partial resistance to artemisinin has emerged and is spreading, threatening malaria control and elimination efforts. The strategy of deploying multiple first-line therapies (MFT) may help mitigate this threat and extend the therapeutic life of current ACTs. (2) Methods: A district-wide pilot quasi-experimental study was conducted, deploying three different ACTs at the public health facility (PHF) level for uncomplicated malaria treatment from December 2019 to December 2020 in the health district (HD) of Kaya, Burkina Faso. Mixed methods, including household and health facility-based quantitative and qualitative surveys, were used to evaluate the pilot programme. (3) Results: A total of 2008 suspected malaria patients were surveyed at PHFs, of which 79.1% were tested by rapid diagnostic test (RDT) with 65.5% positivity rate. In total, 86.1% of the confirmed cases received the appropriate ACT according to the MFT strategy. The adherence level did not differ by study segment (p = 0.19). Overall, the compliance level of health workers (HWs) with MFT strategy was 72.7% (95% CI: 69.7-75.5). The odds of using PHF as the first source of care increased after the intervention (aOR = 1.6; 95% CI, 1.3-1.9), and the reported adherence to the 3-day treatment regimen was 82.1%; (95% CI: 79.6-84.3). Qualitative results showed a high acceptance of the MFT strategy with positive opinions from all stakeholders. (4) Conclusions: Implementing an MFT strategy is operationally feasible and acceptable by stakeholders in the health systems in Burkina Faso. This study provides evidence to support the simultaneous use of multiple first-line artemisinin combination therapies in malaria-endemic countries such as Burkina Faso.

Breaking the cycle of malaria treatment failure.

Treatment of symptomatic malaria became a routine component of the clinical and public health response to malaria after the second world war. However, all antimalarial drugs deployed against malaria eventually generated enough drug resistance that they had to be removed from use. Chloroquine, sulfadoxine-pyrimethamine, and mefloquine are well known examples of antimalarial drugs to which resistance did and still does ready evolve. Artemisinin-based combination therapies (ACTs) are currently facing the same challenge as artemisinin resistance is widespread in Southeast Asia and emerging in Africa. Here, I review some aspects of drug-resistance management in malaria that influence the strength of selective pressure on drug-resistant malaria parasites, as well as an approach we can take in the future to avoid repeating the common mistake of deploying a new drug and waiting for drug resistance and treatment failure to arrive. A desirable goal of drug-resistance management is to reduce selection pressure without reducing the overall percentage of patients that are treated. This can be achieved by distributing multiple first-line therapies (MFT) simultaneously in the population for the treatment of uncomplicated falciparum malaria, thereby keeping treatment levels high but the overall selection pressure exerted by each individual therapy low. I review the primary reasons that make MFT a preferred resistance management option in many malaria-endemic settings, and I describe two exceptions where caution and additional analyses may be warranted before deploying MFT. MFT has shown to be feasible in practice in many endemic settings. The continual improvement and increased coverage of genomic surveillance in malaria may allow countries to implement custom MFT strategies based on their current drug-resistance profiles.

Therapy of Pediatric-Onset Multiple Sclerosis: State of the Art, Challenges, and Opportunities.

Treatment of pediatric-onset multiple sclerosis (POMS) has been tailored after observational studies and data obtained from clinical trials in adult-onset multiple sclerosis (AOMS) patients. There are an increasing number of new therapeutic agents for AOMS, and many will be formally studied for use also in POMS. However, there are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss the current state of the art of POMS therapy and will focus on the newer therapies (oral and infusion disease-modifying drugs) and on those still currently under investigation.

[Clinical post-approval studies as part of the Therapy Allergen Regulation (TAV): A systematic review]. / Klinische Nachzulassungsstudien im Rahmen der Therapieallergene-Verordnung (TAV): Eine systematische Recherche.

With the introduction of the Therapy Allergens Ordinance (TAV) the previously unapproved therapeutic allergens on the existing market need to be checked for their risk-benefit ratio as a basic prerequisite for approval under pharmaceutical law. This process is criticized because it can lead to long transition periods so that patients will probably be treated for two decades with preparations whose effectiveness has not yet been proven and may never be proven. The aim of this work is to list the critical preparations for which no publicly accessible study activity has been recorded since the beginning of the TAV in 2008. For this purpose, the European Clinical Trials Register (clinicaltrialsregister.eu) and the American study register (ClinicalTrials.gov) are systematically searched. The following hypothesis, consistent with the TAV, will be checked: "In the past years, study programs were carried out for the preparations in the process of the TAV - the majority of these preparations are about to be approved by PEI". The hypothesis is refuted with the findings of this work. In fact, no preparation can currently be identified that is about to be TAV approved. 61 preparations are currently in the TAV process; only two preparations have already passed this successfully. If the total of 63 (61+2) preparations are combined in the homologous groups - trees, grasses, mites and mixtures -, there are 33 preparations that can be classified as follows: For the 33 preparations in the TAV process, 36 studies (phase II and III) that may potentially be relevant for TAV were found as part of the screening. For 15 of these studies the results have duly been entered in the European study register. The results of another 13 studies have not been stored in the study register although they are marked as completed. No information has been stored in the European study register for four studies so that the status of these studies remains unclear. Four studies have not yet been completed. Responsible doctors can make recommendations for the prescription of a certain SIT preparation only if there is adequate evidence of its effectiveness. For preparations that have not yet started studies more than ten years after the introduction of the TAV, it is very doubtful whether approval can still be obtained or whether it is even being sought. For the three main inhaled allergens (grasses, trees and mites) there is already a selection of approved, evidence-based and effective alternatives for both subcutaneous (SCIT) and sublingual (SLIT) application from various manufacturers on the market. The use of therapies that have been approved and proven effective is essential in terms of guideline-compliant, sensible care for patients.

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

INTRODUCTION: Natalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk. METHODS: Data from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated. RESULTS: Overall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (n = 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed. CONCLUSION: NTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation.