Impact of preventive chemotherapy on Strongyloides stercoralis: A systematic review and meta-analysis.

BACKGROUND: Strongyloides stercoralis is a neglected soil-transmitted helminth (STH) that leads to significant morbidity in endemic populations. Infection with this helminth has recently been recognised by the World Health Organization (WHO) as a major global health problem to be addressed with ivermectin preventive chemotherapy, and therefore, there is now, the need to develop guidelines for strongyloidiasis control that can be implemented by endemic countries. This study aimed to evaluate the impact of ivermectin preventive chemotherapy (PC) on S. stercoralis prevalence in endemic areas to generate evidence that can inform global health policy. METHODOLOGY/PRINCIPAL FINDINGS: This study was a systematic review and meta-analysis. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and LILACS for literature published between 1990 and 2022 and reporting prevalence of S. stercoralis before and after PC with ivermectin, administered either at school or at community level. The search strategy identified 933 records, eight of which were included in the meta-analysis. Data extraction and quality assessment were carried out by two authors. Meta-analysis of studies based on fecal testing demonstrated a significant reduction of S. stercoralis prevalence after PC: prevalence Risk Ratio (RR) 0.18 (95% CI 0.14-0.23), I2 = 0. A similar trend was observed in studies that used serology for diagnosis: RR 0.35 (95% CI 0.26-0.48), I2 = 4.25%. A sensitivity analysis was carried out for fecal tests where low quality studies were removed, confirming a post-intervention reduction in prevalence. The impact of PC could not be evaluated at different time points or comparing annual vs biannual administration due to insufficient data. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate a significant decrease of S. stercoralis prevalence in areas where ivermectin PC has taken place, supporting the use of ivermectin PC in endemic areas.

Immunotherapy for people with clinically isolated syndrome or relapsing-remitting multiple sclerosis: treatment response by demographic, clinical, and biomarker subgroups (PROMISE)-a systematic review protocol.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system with an increasing worldwide prevalence. Since 1993, more than 15 disease-modifying immunotherapies (DMTs) have been licenced and have shown moderate efficacy in clinical trials. Based on the heterogeneity of the disease and the partial effectiveness of therapies, a personalised medicine approach would be valuable taking individual prognosis and suitability of a chosen therapy into account to gain the best possible treatment effect. The primary objective of this review is to assess the differential treatment effects of all approved DMTs in subgroups of adults with clinically isolated syndrome or relapsing forms of MS. We will analyse possible treatment effect modifiers (TEM) defined by baseline demographic characteristics (gender, age), and diagnostic (i.e. MRI measures) and clinical (i.e. relapses, disability level) measures of MS disease activity. METHODS: We will include all published and accessible unpublished primary and secondary analyses of randomised controlled trials (RCTs) with a follow-up of at least 12 months investigating the efficacy of at least one approved DMT, with placebo or other approved DMTs as control intervention(s) in subgroups of trial participants. As the primary outcome, we will address disability as defined by the Expanded Disability Status Scale or multiple sclerosis functional composite scores followed by relapse frequency, quality of life measures, and side effects. MRI data will be analysed as secondary outcomes. MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL and major trial registers will be searched for suitable studies. Titles and abstracts and full texts will be screened by two persons independently using Covidence. The risk of bias will be analysed based on the Cochrane "Risk of Bias 2" tool, and the certainty of evidence will be assessed using GRADE. Treatment effects will be reported as rate ratio or odds ratio. Primary analyses will follow the intention-to-treat principle. Meta-analyses will be carried out using random-effects models. DISCUSSION: Given that individual patient data from clinical studies are often not available, the review will allow to analyse the evidence on TEM in MS immunotherapy and thus support clinical decision making in individual cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021279665 .

Effects of goal-oriented care for adults with multimorbidity: A systematic review and meta-analysis.

OBJECTIVE: To systematically review the evidence from randomized controlled trials comparing the effects of goal-oriented care against standard care for multimorbid adults. DATA SOURCES/STUDY SETTING: The literature presenting the results of randomized trials assessing the outcomes of goal-oriented care compared with usual care for adults with multimorbidity. STUDY DESIGN: Systematic review and meta-analysis. DATA COLLECTION/EXTRACTION METHODS: We searched the Cochrane Database of Systematic Reviews (CENTRAL), EMBASE, MEDLINE, CINHAL, trial registries such as ClinicalTrial.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP), and the references of eligible trials and relevant reviews. Goal-oriented care was defined as an approach that engages patients, establishes personal goals, and sets targets for patients and clinicians to plan a course of action and measure outcome. We reviewed 228 trials, and 12 were included. We extracted outcome data on quality of life, hospital admission, patients' satisfaction, patient and caregiver burden. Risk of bias was assessed and certainty of evidence was evaluated using GRADE. PRINCIPAL FINDINGS: No study was fully free of bias. No effect was found on quality of life (standardized mean difference [SMD]: 0.05; 95% CI: -0.05 to 0.16) and hospital admission (risk ratio [RR]: 0.87; 95% CI: 0.65 to 1.17). There was a very small effect for patients' satisfaction (SMD: 0.15; 95% CI: 0.00 to 0.29) and caregiver burden (SMD: -0.13; 95% CI: -0.26 to 0.00). Certainty of evidence was low for all outcomes. CONCLUSIONS: No firm conclusions can be reached about the effects of goal-oriented care for multimorbid adults. Future research should overcome the shortcomings of trials assessed in this meta-analysis. Sound application of the indications for research of complex healthcare interventions is warranted.

Clinical and laboratory features of Strongyloides stercoralis infection at diagnosis and after treatment: a systematic review and meta-analysis.

BACKGROUND: The clinical and laboratory characterization of Strongyloides stercoralis infection at diagnosis and after treatment is still poorly defined. OBJECTIVES: The primary objective was to describe the pattern and frequency of clinical and laboratory characteristics associated with S. stercoralis infection. The secondary objectives were (a) comparison of characteristics reported in endemic versus non-endemic areas; and (b) the evaluation of the resolution of identified characteristics after treatment. METHODS: We searched PubMed, EMBASE, LILACS and CENTRAL up to May 2021. Eligible studies were randomized controlled trials (RCTs) for the treatment of S. stercoralis infection and prospective observational studies reporting data on symptoms caused by strongyloidiasis in individuals diagnosed with a highly specific test. Quality assessment was performed to assess the risk of bias. Demographic and clinical data were summarized using descriptive statistics. Meta-analysis was done by pooling the proportion of participants with symptoms with random effects model. RESULTS: Twenty studies were included: nine RCTs and 13 observational studies. Overall, symptoms were reported in 50.4% cases (95% CI 47.6-53.1), and were more often reported in non-endemic (58.6%, 95% CI 55.0-62.2) than in endemic (35.7%, 95% CI 31.4-39.9) areas. The removal of an article of lower quality did not impact on figures. Frequency of symptoms tended to reduce after treatment. Three studies reported the proportion of participants with eosinophilia before and after treatment: 76.9% of participants (95% CI 73.4-80.4) had eosinophilia at diagnosis, reducing to 27.4% (95% CI 24.0-30.7) after treatment. CONCLUSIONS: About half of infected people complain at least of one symptom and almost 70% have eosinophilia. The frequency of symptoms and eosinophilia decreased after treatment, though the association with cure is not clearly defined. Providing relief from symptoms and eosinophilia is another reason, in addition to prevention of disseminated disease, for promoting screening and treatment of individuals with strongyloidiasis.

Theoretical Models of Consciousness: A Scoping Review.

The amount of knowledge on human consciousness has created a multitude of viewpoints and it is difficult to compare and synthesize all the recent scientific perspectives. Indeed, there are many definitions of consciousness and multiple approaches to study the neural correlates of consciousness (NCC). Therefore, the main aim of this article is to collect data on the various theories of consciousness published between 2007-2017 and to synthesize them to provide a general overview of this topic. To describe each theory, we developed a thematic grid called the dimensional model, which qualitatively and quantitatively analyzes how each article, related to one specific theory, debates/analyzes a specific issue. Among the 1130 articles assessed, 85 full texts were included in the prefinal step. Finally, this scoping review analyzed 68 articles that described 29 theories of consciousness. We found heterogeneous perspectives in the theories analyzed. Those with the highest grade of variability are as follows: subjectivity, NCC, and the consciousness/cognitive function. Among sub-cortical structures, thalamus, basal ganglia, and the hippocampus were the most indicated, whereas the cingulate, prefrontal, and temporal areas were the most reported for cortical ones also including the thalamo-cortical system. Moreover, we found several definitions of consciousness and 21 new sub-classifications.

Epidemiological distribution of Echinococcus granulosus s.l. infection in human and domestic animal hosts in European Mediterranean and Balkan countries: A systematic review.

Cystic echinococcosis (CE) is a neglected zoonosis caused by infection with the cestode Echinococcus granulosus sensu lato. We carried out a systematic literature review on E. granulosus s.l. human and animal (cattle, sheep, dog) infection in European Mediterranean and Balkan countries in 2000-2019, to provide a picture of its recent epidemiology in this endemic area. MEDLINE, EMBASE, Scopus, Google Scholar and Open Grey databases were searched. Included cases were: i) for humans, data from hospital records and imaging studies; ii) for dogs, data from necropsy and coprological studies; iii) for ruminants, cases based on slaughter inspection. The NUTS (Nomenclature of Territorial Units for Statistics) classification was used to categorize extracted data in epidemiological units, defined as data referred to one NUTS2 (basic region) in one year time. Data were then aggregated to NUTS1 level (major regions), calculating the average incidence value of included epidemiological units. For prevalence studies covering different epidemiological units, the pooled prevalence was estimated. Data were extracted from 79 publications, 25 on human infection (covering 437 epidemiological units), and 54 on animal infection (52 epidemiological units for cattle, 35 for sheep and 25 for dogs). At NUTS1 level, average annual incidence rates of human CE ranged from 0.10-7.74/100,000; pooled prevalence values ranged from 0.003-64.09% in cattle, 0.004-68.73% in sheep, and 0-31.86% in dogs. Southern and insular Italy, central Spain, Romania and Bulgaria reported the highest values. Bovine data showed a more similar pattern to human data compared to sheep and dogs. Limitation of evidence included the paucity of human prevalence studies, data heterogeneity, and the patchy geographical coverage, with lack of data especially for the Balkans. Our results confirm Italy, Spain, and Eastern Europe being the most affected areas, but data are extremely heterogeneous, geographical coverage very patchy, and human prevalence studies extremely scant. Results also highlight the notorious problem of underreporting of E. granulosus s.l. infection in both humans and animals.

Morbidity Associated with Chronic Strongyloides stercoralis Infection: A Systematic Review and Meta-Analysis.

Strongyloides stercoralis, a worldwide-distributed soil-transmitted helminth, causes chronic infection which may be life threatening. Limitations of diagnostic tests and nonspecificity of symptoms have hampered the estimation of the global morbidity due to strongyloidiasis. This work aimed at assessing S. stercoralis-associated morbidity through a systematic review and meta-analysis of the available literature. MEDLINE, Embase, CENTRAL, LILACS, and trial registries (WHO portal) were searched. The study quality was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) of the association between symptoms and infection status and frequency of infection-associated symptoms were calculated. Six articles from five countries, including 6,014 individuals, were included in the meta-analysis-three were of low quality, one of high quality, and two of very high quality. Abdominal pain (OR 1.74 [CI 1.07-2.94]), diarrhea (OR 1.66 [CI 1.09-2.55]), and urticaria (OR 1.73 [CI 1.22-2.44]) were associated with infection. In 17 eligible studies, these symptoms were reported by a large proportion of the individuals with strongyloidiasis-abdominal pain by 53.1% individuals, diarrhea by 41.6%, and urticaria by 27.8%. After removing the low-quality studies, urticaria remained the only symptom significantly associated with S. stercoralis infection (OR 1.42 [CI 1.24-1.61]). Limitations of evidence included the low number and quality of studies. Our findings especially highlight the appalling knowledge gap about clinical manifestations of this common yet neglected soil-transmitted helminthiasis. Further studies focusing on morbidity and risk factors for dissemination and mortality due to strongyloidiasis are absolutely needed to quantify the burden of S. stercoralis infection and inform public health policies.

Accuracy of molecular biology techniques for the diagnosis of Strongyloides stercoralis infection-A systematic review and meta-analysis.

BACKGROUND: Strongyloides stercoralis infection is a neglected tropical disease which can lead to severe symptoms and even death in immunosuppressed people. Unfortunately, its diagnosis is hampered by the lack of a gold standard, as the sensitivity of traditional parasitological tests (including microscopic examination of stool samples and coproculture) is low. Hence, alternative diagnostic methods, such as molecular biology techniques (mostly polymerase chain reaction, PCR) have been implemented. However, there are discrepancies in the reported accuracy of PCR. METHODOLOGY: A systematic review with meta-analysis was conducted in order to evaluate the accuracy of PCR for the diagnosis of S. stercoralis infection. The protocol was registered with PROSPERO International Prospective Register of Systematic Reviews (record: CRD42016054298). Fourteen studies, 12 of which evaluating real-time PCR, were included in the analysis. The specificity of the techniques resulted high (ranging from 93 to 95%, according to the reference test(s) used). When all molecular techniques were compared to parasitological methods, the sensitivity of PCR was assessed at 71.8% (95% CI 52.2-85.5), that decreased to 61.8% (95% CI 42.0-78.4) when serology was added among the reference tests. Similarly, sensitivity of real-time PCR resulted 64.4% (95% CI 46.2-77.7) when compared to parasitological methods only, 56.5% (95% CI 39.2-72.4) including serology. CONCLUSIONS: PCR might not be suitable for screening purpose, whereas it might have a role as a confirmatory test.

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010.

BACKGROUND: Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. METHODS: Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. RESULTS: Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). CONCLUSIONS: We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.