Genetics of cold-adapted B/Ann Arbor/1/66 influenza virus reassortants: the acidic polymerase (PA) protein gene confers temperature sensitivity and attenuated virulence

The cold-adapted B/Ann Arbor/1/66 influenza virus (ca B/AA/1/66) expresses temperature-sensitive (ts), cold-adapted (ca) and attenuation phenotypes. Reassortants which inherit one or more genes from ca B/AA/1/66 and all other genes from a virulent, wild-type influenza virus, B/Houston/1732/76, were produced and evaluated in order to identify the gene(s) responsible for the ts, ca and attenuation phenotypes. Only reassortants which inherited the PA gene from ca B/AA/1/66 expressed the ts phenotype in MDCK cells at 39 [deg]C. None of the reassortants tested expressed the ca phenotype in embryonated eggs at 25 [deg]C. The virulence of several reassortants was evaluated in ferrets. Inheritance of the PA gene from ca B/AA/1/66 was correlated with significant febrile attentuation and the apparent restriction of viral replication in the lower respiratory tract. Isolation of a virulent, non-ts revertant virus inheriting only the PA gene from ca B/AA/1/66 established a direct relationship between expression of the ts phenotype and attenuated virulence. Evidence for the contribution of at least one other gene from ca B/AA/1/66 to attenuation was observed. Thus, based on the methods used to determine reassortant gene compositions, these results indicate that the PA gene is primarily responsible for attenuation of ca B/AA/1/66 and its reassortants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26616/1/0000157.pd

Can Reproductive Health Voucher Programs Improve Quality of Postnatal Care? A Quasi-Experimental Evaluation of Kenya’s Safe Motherhood Voucher Scheme

This study tests the group-level causal relationship between the expansion of Kenya’s Safe Motherhood voucher program and changes in quality of postnatal care (PNC) provided at voucher-contracted facilities. We compare facilities accredited since program inception in 2006 (phase I) and facilities accredited since 2010-2011 (phase II) relative to comparable non-voucher facilities. PNC quality is assessed using observed clinical content processes, as well as client-reported outcome measures. Two-tailed unpaired t-tests are used to identify differences in mean process quality scores and client-reported outcome measures, comparing changes between intervention and comparison groups at the 2010 and 2012 data collection periods. Difference-in-differences analysis is used to estimate the reproductive health (RH) voucher program’s causal effect on quality of care by exploiting group-level differences between voucher-accredited and non-accredited facilities in 2010 and 2012. Participation in the voucher scheme since 2006 significantly improves overall quality of postnatal care by 39% (p=0.02), where quality is defined as the observable processes or components of service provision that occur during a PNC consultation. Program participation since phase I is estimated to improve the quality of observed maternal postnatal care by 86% (p=0.02), with the largest quality improvements in counselling on family planning methods (IRR 5.0; p=0.01) and return to fertility (IRR 2.6; p=0.01). Despite improvements in maternal aspects of PNC, we find a high proportion of mothers who seek PNC are not being checked by any provider after delivery. Additional strategies will be necessary to standardize provision of packaged postnatal interventions to both mother and new-born. This study addresses an important gap in the existing RH literature by using a strong evaluation design to assess RH voucher program effectiveness on quality improvement

Quality of care assessment in geriatric evaluation and management units: construction of a chart review tool for a tracer condition

<p>Abstract</p> <p>Background</p> <p>The number of elderly people requiring hospital care is growing, so, quality and assessment of care for elders are emerging and complex areas of research. Very few validated and reliable instruments exist for the assessment of quality of acute care in this field. This study's objective was to create such a tool for Geriatric Evaluation and Management Units (GEMUs).</p> <p>Methods</p> <p>The methodology involved a reliability and feasibility study of a retrospective chart review on 934 older inpatients admitted in 49 GEMUs during the year 2002–2003 for fall-related trauma as a tracer condition. Pertinent indicators for a chart abstraction tool, the Geriatric Care Tool (GCT), were developed and validated according to five dimensions: access to care, comprehensiveness, continuity of care, patient-centred care and appropriateness. Consensus methods were used to develop the content. Participants were experts representing eight main health care professions involved in GEMUs from 19 different sites. Items associated with high quality of care at each step of the multidisciplinary management of patients admitted due to falls were identified. The GCT was tested for intra- and inter-rater reliability using 30 medical charts reviewed by each of three independent and blinded trained nurses. Kappa and agreement measures between pairs of chart reviewers were computed on an item-by-item basis.</p> <p>Results</p> <p>Three quarters of 169 items identifying the process of care, from the case history to discharge planning, demonstrated good agreement (kappa greater than 0.40 and agreement over 70%). Indicators for the appropriateness of care showed less reliability.</p> <p>Conclusion</p> <p>Content validity and reliability results, as well as the feasibility of the process, suggest that the chart abstraction tool can gather standardized and pertinent clinical information for further evaluating quality of care in GEMU using admission due to falls as a tracer condition. However, the GCT should be evaluated in other models of acute geriatric units and new strategies should be developed to improve reliability of peer assessments in characterizing the quality of care for elderly patients with complex conditions.</p

A mutation in the PA protein gene of cold-adapted B/Ann Arbor/1/66 influenza virus associated with reversion of temperature sensitivity and attenuated virulence

Reassortant SG3 inherits only the acidic polymerase (PA) protein gene from the cold-adapted B/AA/1/66 influenza virus (ca B/AA/l/66) and all remaining genes from a virulent, wild-type virus. This reassortant demonstrates attenuated virulence in ferrets and expresses a is phenotype characteristic of the ca parent. During virulence evaluation of SG3, a virulent, non-ts revertant virus (designated SG3rFL) was isolated from the lungs of one ferret. In order to determine whether the reversion of SG3 resulted from mutation of the PA gene and/or as the result of extragenic supressor mutations, the revertant PA gene of SG3rFL was transferred to a reassortant (SG3r) inheriting only the revertant PA gene from SG3rFL and all remaining genes from SG3. Reassortant SG3r was non-ts and virulent, indicating that mutation of the PA gene was sufficient for the reversion of the is and attenuation phenotypes expressed by SG3rFL. The nucleotide and predicted amino acid sequences of the SG3rFL PA gene were determined and compared to those of wt and ca B/AA/1 /66. The predicted PA proteins of wt and ca B/AA/1 /66 are known to differ by six amino acid substitutions including a valine to methionine substitution at residue 431. The PA proteins of ca B/AA/1/66 and SG3rFL were distinguished by only the single amino acid substitution of methionine to isoluecine also occurring at residue 431. Thus, the methionine residue was implicated in the attenuation of ca B/AA/1/66 and its reassortants. The hydropathic properties of valine, isoleucine, and methionine suggested that reversion involved the restoration of hydrophobic character at this site.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27363/1/0000388.pd

Sequence comparison of wild-type and cold-adapted B/Ann Arbor/1/66 influenza virus genes

Consensus sequences for both wt and ca B/Ann Arbor/1 /66 viral PB2, PB1, PA, NP, M, and NS genes were directly determined from vRNA using a combination of chemical and chain-termination sequencing methods. There were 105 sites of difference between the wt and ca sets of these six RNA genes. The differences resulted in 26 amino acid substitutions distributed over the six proteins. The sequence changes were compared to the sequences of other known influenza type B wt viruses to pinpoint those changes that were unique to the ca B/Ann Arbor/1/66 virus. Of the 26 amino acid differences, only 11 were unique to the cold-adapted virus. These unique sites were distributed among five of the six genes. The NS protein had no amino acid substitutions. The sequence changes are discussed in terms of their probable mode of origin and selection, and in terms of their importance to the cold-adapted, temperature-sensitive, and attenuation phenotypes of ca B/AA/1 /66 virus. The sequence and organization of the PB2 gene and predicted protein are also given. The PB2 gene was 2396 nucleotides long, and it encoded a predicted protein of 770 amino acids with a molecular weight of 88,035 Da for the wt virus and 88,072 Da for the ca virus. Both proteins were predominantly hydrophilic, and each had an overall charge of +24.5 at pH 7.0.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27362/1/0000387.pd

Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems : A protocol for a qualitative study and a national survey

FADQThis project has been funded by the Instituto de Salud Carlos III, co-financed by the European Regional Development Fund (PI08 90647). The publication of this document has been funded within the framework of collaboration designed for the Quality Plan of the Spanish National Health System, under the agreement signed by the Carlos III Health Institute and the Aragon Health Science Institute as GuiaSalud secretariat. Pablo Alonso-Coello is funded by a Miguel Servet contract by the Instituto de Salud Carlos III (CP09/00137).Background: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. Methods/Design. A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. Discussion. Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere. © 2010 Kotzeva et al; licensee BioMed Central Lt

Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems: a protocol for a qualitative study and a national survey

BACKGROUND: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. METHODS/DESIGN: A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. DISCUSSION: Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere

The role of ethics and ideology in our contribution to global health The topic of this article has vividly interested the author for many years. It is fascinating to him that the issues at stake have not changed for the last 30 years or so. As proof of this – and on purpose – references quoted are both those published before 1985 and after 1995 (Table 1). Considerable material on this topic was already available from the mid 1970s on. The end result has been the (re)construction of a scenario that has been stubborn to change and that looks into most of the, still highly relevant, burning questions of then and now on the issues pertaining to the title of this contribution for debate. It will be of interest to the reader to see how we often need to be reminded of the things our peers had evidence of and wrote about long before us – as the examples of Dr. Virchov and of the Alma Ata Declaration, for instance, show.

What drives public health professionals in their daily work? Presumably it is the appeal of working, either locally or globally, to alleviate the suffering caused by (preventable) ill-health. This article explores the political awareness of health professionals, the political implications of their daily activities and suggests an enhanced role for them in the battle against preventable ill-health worldwide. The starting point for this article is the motivating principles behind these professionals as individuals. It challenges established paradigms in health, medicine, development and academia with a focus on health professionals' political, ethical and ideological motivations and awareness plus the implications of their actions in the realm of global health in the future. It further has implications for the everyday practice of health care providers, public health practitioners, epidemiologists and social scientists in academia

The contribution of staff call light response time to fall and injurious fall rates: an exploratory study in four US hospitals using archived hospital data

Abstract Background Fall prevention programs for hospitalized patients have had limited success, and the effect of programs on decreasing total falls and fall-related injuries is still inconclusive. This exploratory multi-hospital study examined the unique contribution of call light response time to predicting total fall rates and injurious fall rates in inpatient acute care settings. The conceptual model was based on Donabedian's framework of structure, process, and health-care outcomes. The covariates included the hospital, unit type, total nursing hours per patient-day (HPPDs), percentage of the total nursing HPPDs supplied by registered nurses, percentage of patients aged 65 years or older, average case mix index, percentage of patients with altered mental status, percentage of patients with hearing problems, and call light use rate per patient-day. Methods We analyzed data from 28 units from 4 Michigan hospitals, using archived data and chart reviews from January 2004 to May 2009. The patient care unit-month, defined as data aggregated by month for each patient care unit, was the unit of analysis (N = 1063). Hierarchical multiple regression analyses were used. Results Faster call light response time was associated with lower total fall and injurious fall rates. Units with a higher call light use rate had lower total fall and injurious fall rates. A higher percentage of productive nursing hours provided by registered nurses was associated with lower total fall and injurious fall rates. A higher percentage of patients with altered mental status was associated with a higher total fall rate but not a higher injurious fall rate. Units with a higher percentage of patients aged 65 years or older had lower injurious fall rates. Conclusions Faster call light response time appeared to contribute to lower total fall and injurious fall rates, after controlling for the covariates. For practical relevance, hospital and nursing executives should consider strategizing fall and injurious fall prevention efforts by aiming for a decrease in staff response time to call lights. Monitoring call light response time on a regular basis is recommended and could be incorporated into evidence-based practice guidelines for fall prevention.http://deepblue.lib.umich.edu/bitstream/2027.42/112579/1/12913_2011_Article_2004.pd