Global trends in typhoidal salmonellosis: A systematic review

Typhoid and paratyphoid fever continue to significantly contribute to global morbidity and mortality. Disease burden is higher in low-and middle-income settings where surveillance programs are rare and little systematic information exists at population level. This review evaluates national, regional, and global trends in the incidence of typhoid fever and of related morbidity and mortality. A literature search in Medline, Embase, and Web of Science was conducted in June 2016, followed by screening and data extraction in duplicate. Studies reporting blood culture estimates of typhoid or paratyphoid morbidity and mortality were included in the analysis. Five thousand five hundred sixty-three unique records were identified, of which 1978 were assessed for relevance with 219 records meeting the eligibility criteria. Salmonella enterica serotype Typhi was the most commonly reported organism (91%), with the occurrence of typhoidal Salmonella (either incidence or prevalence) being the most commonly reported outcome (78%), followed by typhoid fever mortality, ileal perforation morbidity, and perforation mortality, respectively. Fewer than 50% of studies stratified outcomes by age or urban/rural locality. Surveillance data were available from 29 countries and patient-focused studies were available from 32 countries. Our review presents a mixed picture with declines reported in many regions and settings but with large gaps in surveillance and published data. Regional trends show generally high incidence rates in South Asia, sub-Saharan Africa, and East Asia and Pacific where the disease is endemic in many countries. Significant increases have been reported in certain countries but should be explored in the context of long-term trends and underlying at-risk populations

Involvement of Nlrp5 in the Maintenance of Genome Integrity in Murine Oocytes

Nlrp5, a maternal-effect gene, is required for embryonic progression and female fertility in mice. Previous work indicated an age-related decline in Nlrp5 transcripts in murine oocytes. As maternal age is associated with increased spindle organization defects, studies in this thesis focused on the analysis of meiotic spindle defects in oocytes of Nlrp5-deficient mice. NALP5 protein showed a novel kinetochore-localization pattern, which was disturbed by spindle poisons. Nlrp5-deficient oocytes displayed a higher frequency of spindle abnormalities and chromosomal misalignment. Upon fertilization, these defects translated into increased incidences of multinucleation. As these phenotypes are associated with deficiencies in genome stability, we examined spindle assembly checkpoint (SAC) components. We found that numerous SAC proteins were dysregulated, implying that NALP5 may be critical in sensing oocyte-related SAC defects. We found that Nlrp5-deficient oocytes may have increased DNA damage. Thus, Nlrp5 may be an integral component responsible for preservation of genome integrity in female gametes.MAS

Clinical and economic impact of molecular testing for BRAF fusion in pediatric low-grade Glioma

Abstract Background Treatment personalization via tumor molecular testing holds promise for improving outcomes for patients with pediatric low-grade glioma (PLGG). We evaluate the health economic impact of employing tumor molecular testing to guide treatment for patients diagnosed with PLGG, particularly the avoidance of radiation therapy (RT) for patients with BRAF-fusion. Methods We performed a model-based cost-utility analysis comparing two strategies: molecular testing to determine BRAF fusion status at diagnosis against no molecular testing. We developed a microsimulation to model the lifetime health and cost outcomes (in quality-adjusted life years (QALYs) and 2018 CAD, respectively) for a simulated cohort of 100,000 patients newly diagnosed with PLGG after their initial surgery. Results The life expectancy after diagnosis for individuals who did not receive molecular testing was 39.01 (95% Confidence Intervals (CI): 32.94;44.38) years and 40.08 (95% CI: 33.19;45.76) years for those who received testing. Our findings indicate that patients who received molecular testing at diagnosis experienced a 0.38 (95% CI: 0.08;0.77) gain in QALYs and $1384 (95$-3486; $1204) reduction in costs over their lifetime. Cost and QALY benefits were driven primarily by the avoidance of long-term adverse events (stroke, secondary neoplasms) associated with unnecessary use of radiation. Conclusions We demonstrate the clinical benefit and cost-effectiveness of molecular testing in guiding the decision to provide RT in PLGG. While our results do not consider the impact of targeted therapies, this work is an example of the value of simulation modeling in assessing the long-term costs and benefits of precision oncology interventions for childhood cancer, which can aid decision-making about health system reimbursement

Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis

<div><p>Background</p><p>Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections.</p><p>Objective</p><p>We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression.</p><p>Methods</p><p>We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities.</p><p>Results</p><p>We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m², prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections.</p><p>Conclusion</p><p>Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.</p></div

Pooled prevalence estimates of comorbidities in severe and non-severe cases of flavivirus infections dengue fever and West Nile virus.

<p>Pooled prevalence estimates of comorbidities in severe and non-severe cases of flavivirus infections dengue fever and West Nile virus.</p

Characteristics of studies included in meta-analysis for prevalence of chronic comorbidities in flavivirus infections.

<p>Characteristics of studies included in meta-analysis for prevalence of chronic comorbidities in flavivirus infections.</p

Keywords for the search related terms and synonyms.

<p>Keywords for the search related terms and synonyms.</p

Flowchart of study selection and systematic literature review process.

<p>The flow diagram describes the systematic review of literature on the prevalence of comorbidities in flavivirus infections. A total of 65 unique studies were identified (47 studies for dengue fever and 18 for West Nile virus from an initial 1373 examined titles). aSome studies reported on more than one flavivirus disease. Studies drawn from the same population were not included in the meta-analyses.</p

Meta-analysis for the prevalence of clinical symptoms in flavivirus infections in the selected studies.

<p>Meta-analysis for the prevalence of clinical symptoms in flavivirus infections in the selected studies.</p

Meta-analysis for the frequency of clinical features in severe flavivirus infections in the selected studies.

<p>Meta-analysis for the frequency of clinical features in severe flavivirus infections in the selected studies.</p