Rapid Identification of Paragonimiasis Foci by Lay Informants in Lao People's Democratic Republic

Background

Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases.

Methodology/Principal Findings

The study was carried out in an endemic area of Lao People''s Democratic Republic. Leaders of 49 remote villages in northern Vientiane Province were asked to notify suspected paragonimiasis patients using a four-item questionnaire sent through administrative channels: persons responding positively for having chronic cough (more than 3 weeks) and/or blood in sputum with or without fever. We validated the village leaders'' reports in ten representative villages with a door-to-door survey. We examined three sputa of suspected patients for the presence of Paragonimus eggs and acid fast bacilli. 91.8% of village leaders participated and notified a total of 220 suspected patients; 76.2% were eventually confirmed; an additional 138 suspected cases were found in the survey. Sensitivity of village leaders'' notice for “chronic cough” and “blood in sputum” was 100%; “blood in sputum” alone reached a sensitivity of 85.7%.

Significance

Our approach led to the identification of three previously unknown foci of transmission. A rapid and simple lay-informant questionnaire approach is a promising low-cost community diagnostic tool of paragonimiasis control programs.     

A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with suspected influenza in Hong Kong

Background

Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong.

Methods

We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: “immunofluorescence-assay” (IFA) or “polymerase-chain-reaction” (PCR)-guided oseltamivir treatment, “empirical treatment plus PCR” and “empirical treatment alone”. Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010–2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers'' perspective.

Results

In base-case analysis, “empirical treatment alone” was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that “PCR-guided treatment” would dominate “empirical treatment alone” when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, “empirical treatment alone” and “PCR-guided treatment” were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations.

Conclusions

During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong.     

Misrepresentation of Randomized Controlled Trials in Press Releases and News Coverage: A Cohort Study

Background

Previous studies indicate that in published reports, trial results can be distorted by the use of “spin” (specific reporting strategies, intentional or unintentional, emphasizing the beneficial effect of the experimental treatment). We aimed to (1) evaluate the presence of “spin” in press releases and associated media coverage; and (2) evaluate whether findings of randomized controlled trials (RCTs) based on press releases and media coverage are misinterpreted.

Methods and Findings

We systematically searched for all press releases indexed in the EurekAlert! database between December 2009 and March 2010. Of the 498 press releases retrieved and screened, we included press releases for all two-arm, parallel-group RCTs (n = 70). We obtained a copy of the scientific article to which the press release related and we systematically searched for related news items using Lexis Nexis.“Spin,” defined as specific reporting strategies (intentional or unintentional) emphasizing the beneficial effect of the experimental treatment, was identified in 28 (40%) scientific article abstract conclusions and in 33 (47%) press releases. From bivariate and multivariable analysis assessing the journal type, funding source, sample size, type of treatment (drug or other), results of the primary outcomes (all nonstatistically significant versus other), author of the press release, and the presence of “spin” in the abstract conclusion, the only factor associated, with “spin” in the press release was “spin” in the article abstract conclusions (relative risk [RR] 5.6, [95% CI 2.8–11.1], p<0.001). Findings of RCTs based on press releases were overestimated for 19 (27%) reports. News items were identified for 41 RCTs; 21 (51%) were reported with “spin,” mainly the same type of “spin” as those identified in the press release and article abstract conclusion. Findings of RCTs based on the news item was overestimated for ten (24%) reports.

Conclusion

“Spin” was identified in about half of press releases and media coverage. In multivariable analysis, the main factor associated with “spin” in press releases was the presence of “spin” in the article abstract conclusion.     

Why Most Biomedical Findings Echoed by Newspapers Turn Out to be False: The Case of Attention Deficit Hyperactivity Disorder

Context

Because positive biomedical observations are more often published than those reporting no effect, initial observations are often refuted or attenuated by subsequent studies.

Objective

To determine whether newspapers preferentially report on initial findings and whether they also report on subsequent studies.

Methods

We focused on attention deficit hyperactivity disorder (ADHD). Using Factiva and PubMed databases, we identified 47 scientific publications on ADHD published in the 1990s and soon echoed by 347 newspapers articles. We selected the ten most echoed publications and collected all their relevant subsequent studies until 2011. We checked whether findings reported in each “top 10” publication were consistent with previous and subsequent observations. We also compared the newspaper coverage of the “top 10” publications to that of their related scientific studies.

Results

Seven of the “top 10” publications were initial studies and the conclusions in six of them were either refuted or strongly attenuated subsequently. The seventh was not confirmed or refuted, but its main conclusion appears unlikely. Among the three “top 10” that were not initial studies, two were confirmed subsequently and the third was attenuated. The newspaper coverage of the “top 10” publications (223 articles) was much larger than that of the 67 related studies (57 articles). Moreover, only one of the latter newspaper articles reported that the corresponding “top 10” finding had been attenuated. The average impact factor of the scientific journals publishing studies echoed by newspapers (17.1 n = 56) was higher (p<0.0001) than that corresponding to related publications that were not echoed (6.4 n = 56).

Conclusion

Because newspapers preferentially echo initial ADHD findings appearing in prominent journals, they report on uncertain findings that are often refuted or attenuated by subsequent studies. If this media reporting bias generalizes to health sciences, it represents a major cause of distortion in health science communication.     

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective

To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years.

Design

Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s.

Exposure definition

Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life.

Outcome definition

Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age.

Data synthesis

Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.

Results

We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I² = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I² = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I² = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.

Conclusions

Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.     

Transitions from injection-drug-use-concentrated to self-sustaining heterosexual HIV epidemics: patterns in the international data

Background

Injecting drug use continues to be a primary driver of HIV epidemics in many parts of the world. Many people who inject drugs (PWID) are sexually active, so it is possible that high-seroprevalence HIV epidemics among PWID may initiate self-sustaining heterosexual transmission epidemics.

Methods

Fourteen countries that had experienced high seroprevalence (<20%) HIV epidemics among PWID and had reliable data for injection drug use (IDU) and heterosexual cases of HIV or AIDS were identified. Graphs of newly reported HIV or AIDS cases among PWID and heterosexuals were constructed to identify temporal relationships between the two types of epidemics. The year in which newly reported cases among heterosexuals surpassed newly reported cases among PWID, aspects of the epidemic curves, and epidemic case histories were analyzed to assess whether it was “plausible” or “highly unlikely” that the HIV epidemic among PWID might have initiated the heterosexual epidemic in each country.

Results

Transitions have occurred in 11 of the 14 countries. Two types of temporal relationships between IDU and heterosexual HIV epidemics were identified, rapid high incidence transitions vs. delayed, low incidence transitions. In six countries it appears “plausible” that the IDU epidemic initiated a heterosexual epidemic, and in five countries it appears “highly unlikely” that the IDU epidemic initiated a heterosexual epidemic. A rapid decline in incidence among PWID after the peak year of new cases and national income were the best predictors of the “highly unlikely” initiation of a heterosexual epidemic.

Discussion

Transitions from IDU concentrated epidemics to heterosexual epidemics are common in countries with high seroprevalence among PWID though there are distinct types of transitions. Interventions to immediately reduce HIV incidence among PWID may reduce the likelihood that an IDU epidemic may initiate a heterosexual epidemic.     

Health Risk or Resource? Gradual and Independent Association between Self-Rated Health and Mortality Persists Over 30 Years

Background

Poor self-rated health (SRH) is associated with increased mortality. However, most studies only adjust for few health risk factors and/or do not analyse whether this association is consistent also for intermediate categories of SRH and for follow-up periods exceeding 5–10 years. This study examined whether the SRH-mortality association remained significant 30 years after assessment when adjusting for a wide range of known clinical, behavioural and socio-demographic risk factors.

Methods

We followed-up 8,251 men and women aged ≥16 years who participated 1977–79 in a community based health study and were anonymously linked with the Swiss National Cohort (SNC) until the end of 2008. Covariates were measured at baseline and included education, marital status, smoking, medical history, medication, blood glucose and pressure.

Results

92.8% of the original study participants could be linked to a census, mortality or emigration record of the SNC. Loss to follow-up 1980–2000 was 5.8%. Even after 30 years of follow-up and after adjustment for all covariates, the association between SRH and all-cause mortality remained strong and estimates almost linearly increased from “excellent” (reference: hazard ratio, HR 1) to “good” (men: HR 1.07 95% confidence interval 0.92–1.24, women: 1.22, 1.01–1.46) to “fair” (1.41, 1.18–1.68; 1.39, 1.14–1.70) to “poor”(1.61, 1.15–2.25; 1.49, 1.07–2.06) to “very poor” (2.85, 1.25–6.51; 1.30, 0.18–9.35). Persons answering the SRH question with “don''t know” (1.87, 1.21–2.88; 1.26, 0.87–1.83) had also an increased mortality risk; this was pronounced in men and in the first years of follow-up.

Conclusions

SRH is a strong and “dose-dependent” predictor of mortality. The association was largely independent from covariates and remained significant after decades. This suggests that SRH provides relevant and sustained health information beyond classical risk factors or medical history and reflects salutogenetic rather than pathogenetic pathways.     

Morbidity and risk of subsequent diagnosis of HIV: a population based case control study identifying indicator diseases for HIV infection

Background

Early identification of persons with undiagnosed HIV infection is an important health care issue. We examined associations between diseases diagnosed in hospitals and risk of subsequent HIV diagnosis.

Methods

In this population-based case control study, cases were persons with incident HIV infection diagnosed in Denmark between 1 January 1995 and 1 June 2008. Risk-set sampling was used to identify 19 age- and gender-matched population controls for each HIV case, using the HIV diagnosis date as the index date for both cases and controls. Prior hospital diagnoses obtained from Danish medical databases were first categorized into 22 major disease categories (excluding AIDS-defining diseases except tuberculosis) and then subdivided into 161 subcategories, allowing us to examine specific diseases as potential HIV indicators by conditional logistic regression.

Results

The study included 2,036 HIV cases and 35,718 controls. Persons with the following disease categories had a high risk of HIV diagnosis during the subsequent 5-year period: sexually transmitted infections and viral hepatitis (adjusted odds ratio [aOR] = 12.3, 95% CI: 9.60–15.7), hematological diseases (aOR = 4.28, 3.13–5.85), lower respiratory tract infections (aOR = 3.98, 3.14–5.04)), CNS infections (aOR = 3.44, 1.74–6.80), skin infections (aOR = 3.05, 2.47–3.75), other infections (aOR = 4.64, 3.89–5.54), and substance abuse (aOR = 2.60, 2.06–3.29). Several specific diseases were associated with aORs >20 including syphilis, hepatitis A, non “A” viral hepatitis, herpes zoster, candida infection, endocarditis, thrombocytopenia, and opioid abuse.

Conclusions

Targeted testing for HIV in patients diagnosed with diseases associated with HIV may lead to earlier treatment and thereby reduced morbidity, mortality and HIV transmission.     

The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression

Background

ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation; its role in leukemia propagation and maintenance, however, remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines.

Findings

Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-UP set was significantly enriched for genes included in the “cell activation”, “immune response”, “apoptosis”, “signal transduction” and “development and differentiation” categories, whereas in the E/R KD-DOWN set only the “PI3K/AKT/mTOR signaling” and “hematopoietic stem cells” categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories “stem cell properties”, “B-cell differentiation”, “immune response”, “cell adhesion” and “DNA damage” with RT-qPCR.

Conclusion

Our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with key regulatory functions that shape the biology of this leukemia subtype. E/R may thus indeed constitute the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.     

dATP/ATP, a multifunctional nucleotide, stimulates bacterial cell lysis, extracellular DNA release and biofilm development

Background

Signaling by extracellular adenosine 5′-triphosphase (eATP) is very common for cell-to-cell communication in many basic patho-physiological development processes. Rapid release of ATP into the extracellular environment from distressed or injured eukaryotic cells due to pathogens or other etiological factors can serve as a “danger signal”, activating host innate immunity. However, little is known about how or whether pathogenic bacteria respond to this “danger signal”.

Methods and Principal Findings

Here we report that extracellular dATP/ATP can stimulate bacterial adhesion and biofilm formation via increased cell lysis and extracellular DNA (eDNA) release. We demonstrate that extracellular dATP/ATP also stimulates bacterial adherence in vitro to human bronchial epithelial cells.

Conclusions and Significance

These data suggest that bacteria may sense extracellular dATP/ATP as a signal of “danger” and form biofilms to protect them from host innate immunity. This study reveals a very important and unrecognized phenomenon that both bacteria and host cells could respond to a common important signal molecule in a race to adapt to the presence of one another. We propose that extracellular dATP/ATP functions as an “inter-domain” warning signal that serves to induce protective measures in both Bacterial and Eukaryotic cells.     

Modelling long term disability following injury: comparison of three approaches for handling multiple injuries

Background

Injury is a leading cause of the global burden of disease (GBD). Estimates of non-fatal injury burden have been limited by a paucity of empirical outcomes data. This study aimed to (i) establish the 12-month disability associated with each GBD 2010 injury health state, and (ii) compare approaches to modelling the impact of multiple injury health states on disability as measured by the Glasgow Outcome Scale – Extended (GOS-E).

Methods

12-month functional outcomes for 11,337 survivors to hospital discharge were drawn from the Victorian State Trauma Registry and the Victorian Orthopaedic Trauma Outcomes Registry. ICD-10 diagnosis codes were mapped to the GBD 2010 injury health states. Cases with a GOS-E score >6 were defined as “recovered.” A split dataset approach was used. Cases were randomly assigned to development or test datasets. Probability of recovery for each health state was calculated using the development dataset. Three logistic regression models were evaluated: a) additive, multivariable; b) “worst injury;” and c) multiplicative. Models were adjusted for age and comorbidity and investigated for discrimination and calibration.

Findings

A single injury health state was recorded for 46% of cases (1–16 health states per case). The additive (C-statistic 0.70, 95% CI: 0.69, 0.71) and “worst injury” (C-statistic 0.70; 95% CI: 0.68, 0.71) models demonstrated higher discrimination than the multiplicative (C-statistic 0.68; 95% CI: 0.67, 0.70) model. The additive and “worst injury” models demonstrated acceptable calibration.

Conclusions

The majority of patients survived with persisting disability at 12-months, highlighting the importance of improving estimates of non-fatal injury burden. Additive and “worst” injury models performed similarly. GBD 2010 injury states were moderately predictive of recovery 1-year post-injury. Further evaluation using additional measures of health status and functioning and comparison with the GBD 2010 disability weights will be needed to optimise injury states for future GBD studies.     

Epidemiology of parainfluenza virus types 1, 2 and 3 infections based on virus isolation between 2002 and 2011 in Yamagata,Japan

To clarify the epidemiology of viral acute respiratory infections (ARIs), 305 human parainfluenza virus types 1 (HPIV1), 154 HPIV2 and 574 HPIV3 strains were isolated from 16,962 nasopharyngeal swabs obtained between 2002 and 2011 at pediatric clinics in Yamagata, Japan. The total isolation frequency for HPIV1–3 was 6.1%. Unlike HPIV1 infections, HPIV3 showed clear seasonality with yearly outbreaks in the spring–summer season. HPIV2 tended to appear biannually in autumn–winter. Although no reliable techniques for the laboratory diagnosis of these infections have been established, the present results suggest that HPIV1–3 are an important causative agent of ARIs in children.     

High Incidence of Multiple Viral Infections Identified in Upper Respiratory Tract Infected Children under Three Years of Age in Shanghai, China

Background

Upper respiratory tract infection (URTI) is a major reason for hospitalization in childhood. More than 80% of URTIs are viral. Etiological diagnosis of URTIs is important to make correct clinical decisions on treatment methods. However, data for viral spectrum of URTIs are very limited in Shanghai children.

Methods

Nasopharyngeal swabs were collected from a group of 164 children aged below 3 years who were hospitalized due to acute respiratory infection from May 2009 to July 2010 in Shanghai. A VRDAL multiplex PCR for 10 common respiratory viruses was performed on collected specimens compared with the Seeplex® RV15 ACE Detection kit for 15 respiratory viruses.

Results

Viruses were detected in 84 (51.2%) patients by VRDAL multiplex PCR, and 8 (4.9%) of cases were mixed infections. Using the Seeplex® RV15 ACE Detection kit, viruses were detected in 129 (78.7%) patients, 49 (29.9%) were co-infected cases. Identified viruses included 37 of human rhinovirus (22.6% of cases), 32 of influenza A virus (19.5%), 30 of parainfluenzavirus-2 (18.3%), 23 of parainfluenzavirus-3 (14.0%), 15 of human enterovirus (9.1%), 14 each of parainfluenzavirus-1, respiratory syncytial virus B and adenovirus (8.5%), 8 of coronavirus 229E/NL63 (4.9%), 6 of human bocavirus (3.7%), 5 each of influenza B virus and respiratory syncytial virus A (3.0%), 3 of parainfluenzavirus-4 (1.8%), 2 of coronavirus OC43/HKU1 (1.2%), and 1 human metapneumovirus (0.6%).

Conclusions

A high frequency of respiratory infections (78.7%) and co-infections (29.9%) was detected in children with acute respiratory infection symptoms in Shanghai. The Seeplex® RV15 ACE detection method was found to be a more reliable high throughput tool than VRDAL method to simultaneously detect multiple respiratory viruses.     

Prolonged visual experience in adulthood modulates holistic face perception

Background

Using the well-known composite illusion as a marker of the holistic perception of faces, we tested how prolonged visual experience with a specific population of faces (4- to 6-year-old children) modulates the face perception system in adulthood.

Methodology/Principal Findings

We report a face composite effect that is larger for adult than children faces in a group of adults without experience with children faces (“children-face novices”), while it is of equal magnitude for adults and children faces in a population of preschool teachers (“children-face experts”). When considering preschool teachers only, we observed a significant correlation between the number of years of experience with children faces and the differential face composite effect between children and adults faces. Participants with at least 10 years of qualitative experience with children faces had a larger composite face effect for children than adult faces.

Conclusions/Significance

Overall, these observations indicate that even in adulthood face processes can be reshaped qualitatively, presumably to facilitate efficient processing of the differential morphological features of the frequently encountered population of faces.     

WHO 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe: modeling clinical outcomes in infants and mothers

Background

The Zimbabwean national prevention of mother-to-child HIV transmission (PMTCT) program provided primarily single-dose nevirapine (sdNVP) from 2002–2009 and is currently replacing sdNVP with more effective antiretroviral (ARV) regimens.

Methods

Published HIV and PMTCT models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). We compared five PMTCT regimens at a fixed level of PMTCT medication uptake: 1) no antenatal ARVs (comparator); 2) sdNVP; 3) WHO 2010 guidelines using “Option A” (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy (ART) for women with advanced disease); 4) WHO “Option B” (ART during pregnancy/breastfeeding without advanced disease; lifelong ART with advanced disease); and 5) “Option B+:” lifelong ART for all pregnant/breastfeeding, HIV-infected women. Pediatric (4–6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected.

Results

Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal ARVs) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of sdNVP (13.8 years) or Option B (13.9 years) compared to no antenatal ARVs (14.0 years), Option A (14.0 years), or Option B+ (14.5 years).

Conclusions

Replacement of sdNVP with currently recommended regimens for PMTCT (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both pediatric and maternal outcomes.