Well-being, distress and health status in a population of adolescent students

The present work explores the psychosocial issues emerging from a large cross-sectional study aimed to assess the prevalence, clinical manifestations, and psychosocial correlates of hyperandrogenism in a population of Italian high school students. Participants were 1804 adolescents, aged between 15 and 19 years, who volunteered to fill in a package of self-report questionnaires (including the Psychosocial Index, the Symptom Questionnaire and Ryff’s Psychological Well-Being scales for the assessment of psychological aspects) and undergo a comprehensive physical examination. Significant gender differences were found with regard to psychological distress, with females reporting higher scores compared with males, but not on well-being dimensions. The relationships of well-being to distress were found to be complex. Although inversely associated, well-being and ill-being appeared to be distinct domains of mental functioning. The evaluation of the moderating effects of well-being in the association between stress and psychological distress indicated that well-being may act as a protective factor, contributing to less pronounced psychological distress as stress levels increased. Higher rates of somatic complaints were found among current smokers. However, substance use (i.e., smoking and drug use) was also found to be positively associated with some well-being dimensions. A considerable number of participants were found to present with disordered eating symptoms, particularly females, and associated higher stress levels and lower quality of life. Sport activities were found to favourably affect psychological health. As to clinical signs of hyperandrogenism, a significant impairment in psychosocial functioning was found among females, whereas no effects on psychological measures could be detected among males. Subgroups of adolescents with distinct clinical and psychological characteristics could be identified by means of cluster analysis. The present study provides new insights into better understanding of the complex relationships between well-being, distress and health status in the adolescent population, with important clinical implications.

[Mastitis management in Swiss dairy farms with udder health problems]

The objective of this study was to describe the udder health management in Swiss dairy herds with udder health problems. One hundred dairy herds with a yield-corrected somatic cell count of 200'000 to 300'000 cells/ml during 2010 were selected. Data concerning farm structure, housing system, milking technique, milking procedures, dry-cow and mastitis management were collected during farm visits between September and December 2011. In addition, quarter milk samples were collected for bacteriological culturing from cows with a composite somatic cell count ≥ 150'000 cells/ml. The highest quarter level prevalence was 12.3 % for C. bovis. Eighty-two percent of the pipeline milking machines in tie-stalls and 88 % of the milking parlours fulfilled the criteria for the vacuum drop, and only 74 % of the pipeline milking machines met the criteria of the 10-l-water test. Eighty-five percent of the farms changed their milk liners too late. The correct order of teat preparation before cluster attachment was carried out by 37 % of the farmers only. With these results, Swiss dairy farmers and herd health veterinarians can be directed to common mistakes in mastitis management. The data will be used for future information campaigns to improve udder health in Swiss dairy farms.

Further characterization of the epa gene cluster and Epa polysaccharides of Enterococcus faecalis.

We previously identified a gene cluster, epa (for enterocococcal polysaccharide antigen), involved in polysaccharide biosynthesis of Enterococcus faecalis and showed that disruption of epaB and epaE resulted in attenuation in translocation, biofilm formation, resistance to polymorphonuclear leukocyte (PMN) killing, and virulence in a mouse peritonitis model. Using five additional mutant disruptions in the 26-kb region between orfde2 and OG1RF_0163, we defined the epa locus as the area from epaA to epaR. Disruption of epaA, epaM, and epaN, like prior disruption of epaB and epaE, resulted in alteration in Epa polysaccharide content, more round cells versus oval cells with OG1RF, decreased biofilm formation, attenuation in a mouse peritonitis model, and resistance to lysis by the phage NPV-1 (known to lyse OG1RF), while mutants disrupted in orfde2 and OG1RF_163 (the epa locus flanking genes) behaved like OG1RF in those assays. Analysis of the purified Epa polysaccharide from OG1RF revealed the presence of rhamnose, glucose, galactose, GalNAc, and GlcNAc in this polysaccharide, while carbohydrate preparation from the epaB mutant did not contain rhamnose, suggesting that one or more of the glycosyl transferases encoded by the epaBCD operon are necessary to transfer rhamnose to the polysaccharide. In conclusion, the epa genes, uniformly present in E. faecalis strains and involved in biosynthesis of polysaccharide in OG1RF, are also important for OG1RF shape determination, biofilm formation, and NPV-1 replication/lysis, as well as for E. faecalis virulence in a mouse peritonitis model.

Evaluation of the accuracy of multilevel analysis parameter estimates for intra-cluster correlation in correlated binary data

Many studies in biostatistics deal with binary data. Some of these studies involve correlated observations, which can complicate the analysis of the resulting data. Studies of this kind typically arise when a high degree of commonality exists between test subjects. If there exists a natural hierarchy in the data, multilevel analysis is an appropriate tool for the analysis. Two examples are the measurements on identical twins, or the study of symmetrical organs or appendages such as in the case of ophthalmic studies. Although this type of matching appears ideal for the purposes of comparison, analysis of the resulting data while ignoring the effect of intra-cluster correlation has been shown to produce biased results.^ This paper will explore the use of multilevel modeling of simulated binary data with predetermined levels of correlation. Data will be generated using the Beta-Binomial method with varying degrees of correlation between the lower level observations. The data will be analyzed using the multilevel software package MlwiN (Woodhouse, et al, 1995). Comparisons between the specified intra-cluster correlation of these data and the estimated correlations, using multilevel analysis, will be used to examine the accuracy of this technique in analyzing this type of data. ^

Improvement of antibiotic prescription in outpatient care: a cluster-randomized intervention study using a sentinel surveillance network of physicians.

OBJECTIVES To assess the effectiveness of implementing guidelines, coupled with individual feedback, on antibiotic prescribing behaviour of primary care physicians in Switzerland. METHODS One hundred and forty general practices from a representative Swiss sentinel network of primary care physicians participated in this cluster-randomized prospective intervention study. The intervention consisted of providing guidelines on treatment of respiratory tract infections (RTIs) and uncomplicated lower urinary tract infections (UTIs), coupled with sustained, regular feedback on individual antibiotic prescription behaviour during 2 years. The main aims were: (i) to increase the percentage of prescriptions of penicillins for all RTIs treated with antibiotics; (ii) to increase the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics; (iii) to decrease the percentage of quinolone prescriptions for all cases of exacerbated COPD (eCOPD) treated with antibiotics; and (iv) to decrease the proportion of sinusitis and other upper RTIs treated with antibiotics. The study was registered at ClinicalTrials.gov (NCT01358916). RESULTS While the percentage of antibiotics prescribed for sinusitis or other upper RTIs and the percentage of quinolones prescribed for eCOPD did not differ between the intervention group and the control group, there was a significant increase in the percentage of prescriptions of penicillins for all RTIs treated with antibiotics [57% versus 49%, OR = 1.42 (95% CI 1.08-1.89), P = 0.01] and in the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics [35% versus 19%, OR = 2.16 (95% CI 1.19-3.91), P = 0.01] in the intervention group. CONCLUSIONS In our setting, implementing guidelines, coupled with sustained individual feedback, was not able to reduce the proportion of sinusitis and other upper RTIs treated with antibiotics, but increased the use of recommended antibiotics for RTIs and UTIs, as defined by the guidelines.

The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events.Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods.

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

BACKGROUND A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. METHODS For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. INTERPRETATION The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. FUNDING WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

Effects of Study Area Size on Geographic Characterizations of Health Events: Prostate Cancer Incidence in Southern New England, USA, 1994-1998.

ABSTRACT : BACKGROUND : We consider how representations of geographic variation in prostate cancer incidence across Southern New England, USA may be affected by selection of study area and/or properties of the statistical analysis. METHOD : A spatial scan statistic was used to monitor geographic variation among 35,167 incident prostate cancer cases diagnosed in Massachusetts, Connecticut and Rhode Island from 1994 to 1998, in relation to the 1990 populations of men 20+ years of age living in that region. Results from the combined-states analysis were compared to those from single-states. Impact of scanning procedures set to examine up to 50% or no more than10% of at-risk populations also was evaluated. RESULTS : With scanning set to 50%, 5 locations in the combined-states analysis were identified with markedly distinct incidence rates. Fewer than expected cases were estimated for nearly all Connecticut, Rhode Island and West Central Massachusetts, whereas census tracts on and around Cape Cod, and areas of Southwestern Connecticut and adjacent to greater Boston were estimated to have yielded more than expected incidence. Results of single-state analyses exhibited several discrepancies from the combined-states analysis. More conservative scanning found many more locations with varying incidence, but discrepancies between the combined- and single-state analysis were fewer. CONCLUSION : It is important to acknowledge the conditional nature of spatial analyses and carefully consider whether a true cluster of events is identified or artifact stemming from selection of study area size and/or scanning properties.

Identification of a conserved cluster in the RH domain of GRK critical for activation by GPCRs

One of the most critical aspects of G Protein Coupled Receptors (GPCRs) regulation is their rapid and acute desensitization following agonist stimulation. Phosphorylation of these receptors by GPCR kinases (GRK) is a major mechanism of desensitization. Considerable evidence from studies of rhodopsin kinase and GRK2 suggests there is an allosteric docking site for the receptor distinct from the GRK catalytic site. While the agonist-activated GPCR appears crucial for GRK activation, the molecular details of this interaction remain unclear. Recent studies suggested an important role for the N- and C-termini and domains in the small lobe of the kinase domain in allosteric activation; however, neither the mechanism of action of that site nor the RH domain contributions have been elucidated. To search for the allosteric site, we first indentified evolutionarily conserved sites within the RH and kinase domains presumably deterministic of protein function employing evolutionary trace (ET) methodology and crystal structures of GRK6. Focusing on a conserved cluster centered on helices 3, 9, and 10 in the RH domain, key residues of GRK5 and 6 were targeted for mutagenesis and functional assays. We found that a number of double mutations within helices 3, 9, and 10 and the N-terminus markedly reduced (50–90%) the constitutive phosphorylation of the β-2 Adrenergic Receptor (β2AR) in intact cells and phosphorylation of light-activated rhodopsin (Rho*) in vitro as compared to wild type (WT) GRK5 or 6. Based on these results, we designed peptide mimetics of GRK5 helix 9 both computationally and through chemical modifications with the goal of both confirming the importance of helix 9 and developing a useful inhibitor to disrupt the GPCR-GRK interaction. Several peptides were found to block Rho* phosphorylation by GRK5 including the native helix 9 sequence, Peptide Builder designed-peptide preserving only the key ET residues, and chemically locked helices. Most peptidomimetics showed inhibition of GRK5 activity greater than 80 % with an IC50 of ∼ 30 µM. Alanine scanning of helix 9 has further revealed both essential and non-essential residues for inhibition. Importantly, substitution of Arg 169 by an alanine in the native helix 9-based peptide gave an almost complete inhibition at 30 µM with an IC50 of ∼ 10 µM. In summary we report a previously unrecognized crucial role for the RH domain of GRK5 and 6, and the subsequent identification of a lead peptide inhibitor of protein-protein interaction with potential for specific blockade of GPCR desensitization. ^

Infectious diseases, immune status, and health insurance among child care providers in Houston, Texas

The objectives of this study were to compare female child-care providers with female university workers and with mothers of children in child-care centers for: (1) frequency of illness and work loss days due to infectious diseases, (2) prevalence of antibodies against measles, rubella, mumps, hepatitis B, hepatitis A, chickenpox and cytomegalovirus (CMV), and (3) status regarding health insurance and job benefits.^ Subjects from twenty child-care centers and twenty randomly selected departments of a university in Houston, Texas were studied in a cross-sectional fashion.^ A cluster sample of 281 female child-care providers from randomly selected child-care centers, a cluster sample of 286 university workers from randomly selected departments and a systematic sample of 198 mothers of children from randomly selected child-care centers.^ Main outcome measures were: (1) self-reported frequency of infectious diseases and number of work-days lost due to infectious diseases; (2) presence of antibodies in blood; and (3) self-reported health insurance and job benefits.^ In comparison to university workers, child-care providers reported a higher prevalence of infectious diseases in the past 30 days; lost three times more work-days due to infectious diseases; and were more likely to have anti-core antibodies against hepatitis B (odds ratio = 3.16 95% CI 1.27-7.85) and rubella (OR 1.88, 95% CI 1.02-3.45). Child-care providers had less health insurance and job-related benefits than mothers of children attending child-care centers.^ Regulations designed to reduce transmission of vaccine and non-vaccine preventable diseases in child-care centers should be strictly enforced. In addition policies to improve health insurance and job benefits of child-care providers are urgently needed. ^

Kawasaki syndrome: Cluster analysis of incident cases presenting to a pediatric tertiary care hospital in Texas from January 1, 2005 to December 31, 2009

Background: Despite almost 40 years of research into the etiology of Kawasaki Syndrome (KS), there is little research published on spatial and temporal clustering of KS cases. Previous analysis has found significant spatial and temporal clustering of cases, therefore cluster analyses were performed to substantiate these findings and provide insight into incident KS cases discharged from a pediatric tertiary care hospital. Identifying clusters from a single institution would allow for prospective analysis of risk factors and potential exposures for further insight into KS etiology. ^ Methods: A retrospective study was carried out to examine the epidemiology and distribution of patients presenting to Texas Children’s Hospital in Houston, Texas, with a diagnosis of Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) upon discharge from January 1, 2005 to December 31, 2009. Spatial, temporal, and space-time cluster analyses were performed using the Bernoulli model with case and control event data. ^ Results: 397 of 102,761 total patients admitted to Texas Children’s Hospital had a principal or secondary diagnosis of Acute Febrile MCLS upon over the 5 year period. Demographic data for KS cases remained consistent with known disease epidemiology. Spatial, temporal, and space-time analyses of clustering using the Bernoulli model demonstrated no statistically significant clusters. ^ Discussion: Despite previous findings of spatial-temporal clustering of KS cases, there were no significant clusters of KS cases discharged from a single institution. This implicates the need for an expanded approach to conducting spatial-temporal cluster analysis and KS surveillance given the limitations of evaluating data from a single institution.^

Burden of invasive pneumococcal disease in Harris County, Texas (2003--2010) and the implication for enhanced public health surveillance of isolates

Invasive pneumococcal disease (IPD) causes significant health burden in the US, is responsible for the majority of bacterial meningitis, and causes more deaths than any other vaccine preventable bacterial disease in the US. The estimated National IPD rate is 14.3 cases per 100,000 population with a case-fatality rate of 1.5 cases per 100,000 population. Although cases of IPD are routinely reported to the local health department in Harris County Texas, the incidence (IR) and case-fatality (CFR) rates have not been reported. Additionally, it is important to know which serotypes of S. pneumoniae are circulating in Harris County Texas and to determine if ‘replacement disease’ is occurring. ^ This study reported incidence and case-fatality rates from 2003 to 2009, and described the trends in IPD, including the IPD serotypes circulating in Harris County Texas during the study period, particularly in 2008 and 2010. Annual incidence rates were calculated and reported for 2003 to 2009, using complete surveillance-year data. ^ Geographic information system (GIS) software was used to create a series of maps of the data reported during the study period. Cluster and outlier analysis and hot spot analysis were conducted using both case counts by census tract and disease rate by census tract. ^ IPD age- and race-adjusted IR for Harris County Texas and their 95% confidence intervals (CIs) were 1.40 (95% CI 1.0, 1.8), 1.71 (95% CI 1.24, 2.17), 3.13 (95% CI 2.48, 3.78), 3.08 (95% CI 2.43, 3.74), 5.61 (95% CI 4.79, 6.43), 8.11 (95% CI 7.11, 9.1), and 7.65 (95% CI 6.69, 8.61) for the years 2003 to 2009, respectively (rates were age- and race-adjusted to each year's midyear US population estimates). A Poisson regression model demonstrated a statistically significant increasing trend of about 32 percent per year in the IPD rates over the course of the study period. IPD age- and race-adjusted case-fatality rates (CFR) for Harris County Texas were also calculated and reported. A Poisson regression model demonstrated a statistically significant increasing trend of about 26 percent per year in the IPD case-fatality rates from 2003 through 2009. A logistic regression model associated the risk of dying from IPD to alcohol abuse (OR 4.69, 95% CI 2.57, 8.56) and to meningitis (OR 2.42, 95% CI 1.46, 4.03). ^ The prevalence of non-vaccine serotypes (NVT) among IPD cases with serotyped isolates was 98.2 percent. In 2008, the year with the sample more geographically representative of all areas of Harris County Texas, the prevalence was 96 percent. Given these findings, it is reasonable to conclude that ‘replacement disease’ is occurring in Harris County Texas, meaning that, the majority of IPD is caused by serotypes not included in the PCV7 vaccine. Also in conclusion, IPD rates increased during the study period in Harris County Texas.^

Mixture modelling for cluster analysis

Cluster analysis via a finite mixture model approach is considered. With this approach to clustering, the data can be partitioned into a specified number of clusters g by first fitting a mixture model with g components. An outright clustering of the data is then obtained by assigning an observation to the component to which it has the highest estimated posterior probability of belonging; that is, the ith cluster consists of those observations assigned to the ith component (i = 1,..., g). The focus is on the use of mixtures of normal components for the cluster analysis of data that can be regarded as being continuous. But attention is also given to the case of mixed data, where the observations consist of both continuous and discrete variables.

A pragmatic 2 × 2 × 2 factorial cluster randomized controlled trial of educational outreach visiting and case conferencing in palliative care—methodology of the Palliative Care Trial [ISRCTN 81117481]

The demand for palliative care is increasing, yet there are few data on the best models of care nor well-validated interventions that translate current evidence into clinical practice. Supporting multidisciplinary patient-centered palliative care while successfully conducting a large clinical trial is a challenge. The Palliative Care Trial (PCT) is a pragmatic 2 x 2 x 2 factorial cluster randomized controlled trial that tests the ability of educational outreach visiting and case conferencing to improve patient-based outcomes such as performance status and pain intensity. Four hundred sixty-one consenting patients and their general practitioners (GPs) were randomized to the following: (1) GP educational outreach visiting versus usual care, (2) Structured patient and caregiver educational outreach visiting versus usual care and (3) A coordinated palliative care model of case conferencing versus the standard model of palliative care in Adelaide, South Australia (3:1 randomization). Main outcome measures included patient functional status over time, pain intensity, and resource utilization. Participants were followed longitudinally until death or November 30, 2004. The interventions are aimed at translating current evidence into clinical practice and there was particular attention in the trial's design to addressing common pitfalls for clinical studies in palliative care. Given the need for evidence about optimal interventions and service delivery models that improve the care of people with life-limiting illness, the results of this rigorous, high quality clinical trial will inform practice. Initial results are expected in mid 2005. (c) 2005 Elsevier Inc. All rights reserved.