Modeling seasonal variation in rotavirus hospitalizations for use in evaluating the effect of rotavirus vaccine

Every year rotavirus epidemic repeats in cooler months of the year in temperate countries, but the size of the epidemic may often vary. Such seasonal variation needs to be considered when the effect of rotavirus vaccine is predicted before vaccine introduction or it is evaluated after vaccine introduction. A computer program based on a stochastic decision tree model was developed to produce stochastic variation, which was used as a proxy for seasonal variation, in the number of rotavirus hospitalizations. When the model was applied to a hypothetical community with a birth cohort of 1,000 children in Japan, it predicted the occurrence of up to 29% of stochastic variation from the average number of rotavirus hospitalizations. Then, the model was applied for use in evaluating the effect of rotavirus vaccine in two different scenarios regarding vaccine use in the community: a scenario where rotavirus vaccine was introduced only into the private sector, and another where it was incorporated into the universal immunization program. In the former scenario, an average of 23% reduction in the number of rotavirus hospitalizations was predicted, but this level of reduction would be obscured due to seasonal variation. In the latter scenario, an average of 74% reduction was predicted, which would be beyond seasonal variation. This model will be useful to inform stakeholders and policymakers how vaccine introduction will change the burden of rotavirus disease under different scenarios of vaccine implementation. J. Med. Virol. 82:1468–1474, 2010. © 2010 Wiley‐Liss, Inc.     

Seasonal variation of Pneumocystis jirovecii infection: analysis of underlying climatic factors

Pneumocystis jirovecii causes severe pneumonia (PCP) in immunocompromised patients. Seasonal changes of PCP incidence may be associated with climate changes. In this first study using multiple linear regression statistics to assess monthly climatic data and Pneumocystis , PCP incidence was positively correlated with mean temperature, but not with rainfall or wind strength.     

HUMA: A platform for the analysis of genetic variation in humans

The completion of the human genome project at the beginning of the 21st century, along with the rapid advancement of sequencing technologies thereafter, has resulted in exponential growth of biological data. In genetics, this has given rise to numerous variation databases, created to store and annotate the ever‐expanding dataset of known mutations. Usually, these databases focus on variation at the sequence level. Few databases focus on the analysis of variation at the 3D level, that is, mapping, visualizing, and determining the effects of variation in protein structures. Additionally, these Web servers seldom incorporate tools to help analyze these data. Here, we present the Human Mutation Analysis (HUMA) Web server and database. HUMA integrates sequence, structure, variation, and disease data into a single, connected database. A user‐friendly interface provides click‐based data access and visualization, whereas a RESTful Web API provides programmatic access to the data. Tools have been integrated into HUMA to allow initial analyses to be carried out on the server. Furthermore, users can upload their private variation datasets, which are automatically mapped to public data and can be analyzed using the integrated tools. HUMA is freely accessible at https://huma.rubi.ru.ac.za .     

Readability assessment of vaccine information: A systematic review for addressing vaccine hesitancy

ObjectiveVaccine hesitancy is a problem attracting growing attention and concern. Communication can be an effective tool to counteract vaccine hesitancy and promote optimal vaccine uptake. Readability has been recognized as one of the more important aspects of health communication for achieving good health literacy. We reviewed studies of readability assessment in the area of vaccine communication.MethodsWe conducted a systematic literature search in September 2020, using four online databases (Medline, CINAHL, PsycArticles, and PsycINFO). We included studies that assessed the readability level of online and offline vaccine information materials.ResultsWe found 12 articles that were appropriate for inclusion. Ten of the studies were published after 2016. The readability levels of the majority of the materials assessed were found to be difficult and higher than 8th-grade level.ConclusionReadability assessments of vaccine information are scarce. The limited evidence shows that the readability level of vaccine information supplied by health care providers is more difficult to read than recommended. More studies on the readability of vaccine information are recommended.Practice implicationsDifficulty reading vaccine information may influence attitudes toward acceptance of or hesitancy to take vaccines. It is recommended that health care professionals use guidelines and tools to create easy-to-read vaccine information.     

A twin analysis of dietary intake: Evidence for a need to control for possible environmental differences in MZ and DZ twins

In the NHLI Twin Study MZ twins are shown to get together substantially more often than DZ twins. With this result as an indicator of differences in shared environment, the assumption of equal shared environmental variation for MZ and DZ twins is assessed using nutritional data calculated from a food frequency questionnaire. Six nutrients show significant genetic variance for the total sample. However, when stratified on the basis of how frequently twins see each other, none of the nutrients shows significant genetic variance for both strata. A similar pattern is seen for several individual items from the questionnaire. In addition, four of the nutrients show significant correlation between the absolute difference in the nutrient intake of MZ twin pairs and how often they get together. These data appear to show that unequal environmental effects may lead to falsely high estimates of genetic variance for nutrient intake.     

International variation in adherence to referral guidelines for suspected cancer: a secondary analysis of survey data

Background

Variation in cancer survival persists between comparable nations and appears to be due, in part, to primary care practitioners (PCPs) having different thresholds for acting definitively in response to cancer-related symptoms.

Aim

To explore whether cancer guidelines, and adherence to them, differ between jurisdictions and impacts on PCPs’ propensity to take definitive action on cancer-related symptoms.

Design and setting

A secondary analysis of survey data from six countries (10 jurisdictions) participating in the International Cancer Benchmarking Partnership.

Method

PCPs’ responses to five clinical vignettes presenting symptoms and signs of lung (n = 2), colorectal (n = 2), and ovarian cancer (n = 1) were compared with investigation and referral recommendations in cancer guidelines.

Results

Nine jurisdictions had guidelines covering the two colorectal vignettes. For the lung vignettes, although eight jurisdictions had guidelines for the first, the second was covered by a Swedish guideline alone. Only the UK and Denmark had an ovarian cancer guideline. Survey responses of 2795 PCPs (crude response rate: 12%) were analysed. Guideline adherence ranged from 20–82%. UK adherence was lower than other jurisdictions for the lung vignette covered by the guidance (47% versus 58%; P <0.01) but similar (45% versus 46%) or higher (67% versus 38%; P <0.01) for the two colorectal vignettes. PCPs took definitive action least often when a guideline recommended a non-definitive action or made no recommendation. UK PCPs adhered to recommendations for definitive action less than their counterparts (P <0.01). There wasno association between jurisdictional guideline adherence and 1-year survival.

Conclusion

Cancer guideline content is variable between similarly developed nations and poor guideline adherence does not explain differential survival. Guidelines that fail to cover high-risk presentations or that recommend non-definitive action may reduce definitive diagnostic action.     

Routine psychosocial assessment of women in the antenatal period: frequency of risk factors and implications for clinical services

Summary Routine psychosocial assessment was introduced at an Australian public hospitals antenatal clinic in 2001. After modification, this assessment consists of 12 questions together with the Edinburgh Depression Scale (EDS). Data are reported for responses to these questions from over 2,000 English-speaking women presenting to the clinic in a 12-month period. These 12 questions and the EDS were categorised into seven risk domains, with 12% of the women (n=260) having three or more of these risk domains. Referral information to one of our two clinical services shows that 6.7% of women assessed in the antenatal clinic become clients having face–face counselling, and a further 7.2% have just telephone contact with this specialist perinatal mental health service. This information should prove useful for services considering implementing routine psychosocial assessments (or screening) in the antenatal period.     

Risk factors for bone loss in the hip of 75-year-old women: A 4-year follow-up study

Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in one-hundred and sixty-two 75-year-old women. Bone mineral density (BMD, g/cm²) was measured with dual X-ray absorptiometry (DXA) at baseline and after 4 years. The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), serum values of biochemical markers and hormones, nutritional and lifestyle factors according to a questionnaire was assessed.     

A novel method for the detection of variation in solid-phase immobilised antibody concentration and its possible application in quality control in immunoassay

Variation of solid-phase antibody concentration could give rise to poor intra- and interassay precision. A new method to detect this variation is reported. Pooled sera with thyroxine (T4) values at the low, medium, and high ranges were assayed in duplicate using anti-T4-coated polystyrene beads. The antigen-antibody complexes were dissociated with methanol-water mixture and the antibodies re-used for subsequent T4 assays in which the same beads were used with the same set of standards and pooled sera. A second set of assays using randomised beads after each assay-wash cycle were also carried out. The variations in weights and surface structures of the beads were also studied. The variation of T4 results of group methods using polyethylene glycol in an external quality control program was also compared with that of covalently linked solid-phase particulate antibody methods over 2 periods. The experimental results showed that there was bead-to-bead variation of antibody concentration which could give rise to poor precision. Rigorous control of the immobilised antibody concentration could further improve the assay performance.     

Scope of coverage of medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine: A curriculum analysis

We appraised the scope of medical genetics and genomics concepts covered in the pre-clerkship programs of Canadian faculties of medicine through an analysis of course objectives. All course objectives linked to medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine were compiled. From this, the fraction of objectives dedicated to medical genetics and genomics was calculated. Course objectives were also categorized according to a curriculum and a competency classification. Of the 17 Canadian faculties of medicine, the complete set of course syllabi (5 faculties) or the listing of learning objectives (4 faculties) were obtained and reviewed. The fraction of learning objectives dedicated to medical genetics and genomics varied between 0.65% and 5.05%. From the objectives classification, “foundational knowledge” was most frequently covered (64% of the compiled objectives), while topics such as: “ethics and professionalism,” “communicate genetics information,” and “obtain specialist help” were covered by less than 5%. Coverage of medical genetics and genomics in pre-clerkship programs of Canadian faculties of medicine appears to be low. Genetics and genomics are playing a rapidly expanding role in healthcare and clinical practice and educational programs should consider this new reality.     

Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta‐analysis in four European populations

Attention‐deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4–8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120 bp duplication in the promoter and 48 bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single‐marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiple‐marker meta‐analysis showed a nominal association (P = 0.02) of the L‐4R haplotype (dup120bp‐48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R‐6R haplotype (3′UTR VNTR‐intron 8 VNTR) in the same dataset, we further tested for gene × gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene. © 2011 Wiley‐Liss, Inc.     

Quantification of dome formation by image analysis in LLC-PK1 renal cells: A sensitive method for the assessment of in vitro nephrotoxicity

Summary A procedure is described for measuring dome morphologic parameters of LLC-PK₁ cells in culture. The method is based on an automated image analysis system directly connected to a stereomicroscope, combined with a stable staining technique of domes. Using well-defined and standardized culture conditions, and taking full advantage of video image potential, we have studied dome evolution during 7 days in culture. Moreover, after measuring the total surface of domes and the number of domes after a treatment by cisplatin, a well-known nephrotoxic agent, we found a dose-dependent decrease in both parameters. The total surface of dome formation seemed to be the most relevant end-point for the estimation of chemical effects. These results point out the interest of this method for cytotoxicity studies on the epithelial renal cell line LLC-PK₁ in relation to xenobiotics nephrotoxicity potential.     

CEST MRI with distribution‐based analysis for assessment of early stage disease activity in a mouse model of multiple sclerosis: An initial study

Imaging biomarkers that can detect pathological changes at an early stage of multiple sclerosis (MS) may allow earlier therapeutic intervention with an improved outcome. Using a mouse model of MS, termed as experimental autoimmune encephalomyelitis (EAE), we performed chemical exchange saturation transfer (CEST) MRI at a very early stage before symptom onset (6 days post‐induction) for assessment of changes in tissues that appear “normal” with conventional MRI. The collected CEST Z‐spectra signals (S_sat/S₀) were analyzed using a histogram‐guided method to determine the contributions from various offset frequencies. Histogram analysis showed that EAE mice exhibit a more heterogeneous distribution with lower peak heights in the hindbrain compared with naïve mice at saturation offsets of 1 and 2 ppm. At these two offsets, both the mean S_sat/S₀ and the mean MTR_asym values in the cerebellum and brain stem are significantly different between EAE and naïve mice (P < 0.05). Immunofluorescent staining validated the presence of neuroinflammation, with IBA1‐positive cells detected throughout the hindbrain including the cerebellum and brain stem. Follow‐up MRI at the symptom onset (score = 1.5–2.5, 13 days post‐induction) confirmed gadolinium‐enhanced periventricular lesions. CEST Z‐spectra signals also changed by this time. The proposed three‐level histogram‐oriented analysis is simple to execute and robust for detecting subtle changes in Z‐spectra signals, which does not require a priori knowledge of damage locations or contributing offset components. CEST MRI signals at 1 and 2 ppm were sensitive to the subtle pathological changes at an early stage in EAE mice, and have potential as novel imaging biomarkers complementary to functional and physiological MRI measures.     

Risk factors for the development of bronchiolitis obliterans in children with severe adenovirus pneumonia: A retrospective study with dose-response analysis

To investigate and analyze the relevant risk factors for bronchiolitis obliterans (BO) in children with severe adenovirus pneumonia, a retrospective study of children with severe adenovirus pneumonia was performed in 34 cases that developing BO and 105 cases not developing BO in Children's hospital of Chongqing Medical University from January 2015 to February 2019. The multivariate logistic regression analysis was used to identify factors which were significantly associated with development of BO after the univariate analysis, and receiver operating characteristic (ROC) curve analysis was performed to find out the cut-off value for the significant relevant factors. A nonlinear dose-response relationship between risk factors and the risk of BO was assessed by restricted cubic spline model. Three factors were independently associated with development of BO, which were length of fever (OR 1.129, 95% CI 1.033-1.234), dyspnea (OR 3.922, 95% CI 1.060-14.514) and invasive mechanical ventilation (OR 6.861, 95% CI 1.854-25.387). The cut-off value of length of fever were 10.5 days. A linear dose-response relationship between length of fever and occurrence of BO was observed (P = .57 for nonlinearity). Children with severe adenovirus pneumonia who have a longer duration of fever (especially more than 10.5 days), have dyspnea or require invasive mechanical ventilation in the acute phase are more likely to develop BO.     

Risk factors for severe complications of the novel influenza A (H1N1): analysis of patients hospitalized in Italy

Eighty-one patients affected by the novel influenza A (H1N1), hospitalized in North-western Italy, were studied. The median age was 32 years (range 1–81 years). Fifty-six (69%) had an underlying medical condition, including lung disorders (asthma or chronic obstructive pulmonary disease) in 34% and obesity in 25%. Fifty percent of them had pneumonia, 12% were admitted to the intensive care unit and 3% died. Antiviral treatment was initiated in 75% of patients started within 48 h. Older age and lung and neurocognitive disorders were associated with severe disease and death.     

Community and school violence as significant risk factors for school climate and bonding of teachers in Chile: A national hierarchical multilevel analysis

Community and school violence involve aggressive behaviors among youth and adults. Researchers have focused mostly on aggression among students without considering teachers as victims of violence. The study's purpose was to examine the consequences of community violence, school violence, and school climate on the levels of teacher's bonding to the school. We examined data of 5733 teachers from 510 schools in 68 different communities in Chile. We used Hierarchical Linear Modeling to examine the relationship between the individual, school, and community‐level variables. We found direct associations with school bonding at the individual level for victim school violence, school climate, size and type of school, and violence in the community at the community level. Our results highlight the importance of school violence prevention from a comprehensive perspective, starting at the community level, followed by the school to provide more teacher's support.