Development Of Evidence-based Clinical Guidelines Research Articles

Capacity Building in Pediatric Critical Care-Global Health Research and Education: The Blantyre Experience.

Pediatric critical care medicine (PCCM), as it is practiced in high-income countries, is focused on specialized medical care for the most vulnerable pediatric patient populations. However, best practices for provision of that care globally are lacking. Thus, PCCM research and education programming can potentially fill significant knowledge gaps by facilitating the development of evidence-based clinical guidelines that reduce child mortality on a global scale. Malaria remains a leading cause of pediatric mortality worldwide. The Blantyre Malaria Project (BMP) is a research and clinical care collaborative that has focused on reducing the public health burden of pediatric cerebral malaria in Malawi since 1986. In 2017, the requirements of a new research study led to the creation of PCCM services in Blantyre, creating the opportunity to establish a PCCM-Global Health Research Fellowship by BMP in collaboration with the University of Maryland School of Medicine. In this perspective piece, we reflect on the evolution of the PCCM-Global Health research fellowship. Although the specifics of this fellowship are out of the scope of this perspective, we discuss the context allowing for the development of this program and explore some early lessons learned to consider for future capacity-building efforts in the future of PCCM-Global Health research.

Influence of Diabetes Mellitus on Oncological Outcomes for Patients Living With Cancer.

The purpose of this meta-analysis was to examine the association between preexisting diabetes in persons living with cancer on diabetes and oncology-related health outcomes. Understanding this association is of priority because the incidence of both cancer and diabetes mellitus is increasing worldwide. A comprehensive review of the literature was conducted in collaboration with an expert health sciences librarian. Two authors independently conducted the screening, data collection, and extraction processes. The risk of bias was assessed using several tools, depending on the study design. Relative risks with 95% confidence intervals were calculated. The alpha threshold was 0.05. All analyses were performed using R statistical software (Metaphor and Demeter packages). A total of 45 studies met the selection criteria, but 23 were excluded from the synthesis because they did not have the ranked outcome or correct comparison (persons with and without diabetes), totaling 22 studies included in the meta-analysis. In comparison to participants without preexisting diabetes, participants with preexisting diabetes and cancer were found to have a significantly higher risk of infection and cardiovascular, neurological, gastrointestinal, hepatic, and renal complications. Concurrent preexisting diabetes and cancer were also associated with increased health care service utilization and length of hospital stay. The findings from this review highlight the importance of optimal concurrent management of both diseases by overcoming the compartmentalization of medical specializations through (1) integrated, multidisciplinary, shared, and coordinated clinical care pathways between oncology and diabetes health care providers/teams and (2) the continued development of evidence-based clinical guidelines.

COPD in Africa: risk factors, hospitalisation, readmission and associated outcomes—a systematic review and meta-analysis

BackgroundThis review aims to synthesise available evidence on the prevalence of chronic obstructive pulmonary disease (COPD), associated risk factors, hospitalisations and COPD readmissions in Africa.MethodUsing the Met-Analyses and Systematic Reviews...

Development of Evidence-Based Clinical Guidelines of Non-Surgical Intervention for Arteriovenous Fistula Failure in Dialysis Patients

<p>超過六成血液透析病人，曾因自體瘻管障礙及失效需外科介入進行瘻管重建術，倘若無良好的預防措施及追蹤，病人瘻管需再次行外科手術的比率上升，進而增加醫療成本的耗損。本指引透過五個階段建置「以非外科介入預防透析病人自體瘻管失效之臨床照護指引」，第一階段成立指引發展小組；第二階段進行2018年前的文獻搜尋及評讀，共篩選出17篇文獻；第三階段依據2015 年蘇格蘭指引發展組織（Scottish Intercollegiate Guidelines Network, SIGN）之證據等級評定各項指引之建議強度，共建置內含23項目之處置初稿（未含指引範圍界定）；第四階段邀請10位臨床相關領域專家，進行處置初稿之專家效度分析及修改；第五階段邀請46位臨床照護人員、及10位透析病人進行指引之可行性調查，最後完成具有21項目的指引處置內容。本指引共包含五個構面：指引範圍界定4項、藥物在自體瘻管失效上的預防3項、透析治療中的照護措施6項、居家照護要點4項，及常規追蹤與處置8項，共25 個項目。期許本指引能協助血液透析病人預防自體瘻管失效，以降低廔管手術重建率，進而減少醫療成本的耗費</p> <p> </p><p>More than 60% of hemodialysis patients need surgical interventions for arteriovenous fistula stenosis or failure. Without adequate preventive treatments and follow-up actions, a high surgery rate resulting in increased medical costs is anticipated. The “ Clinical Care Guidelines of Non-Surgical Interven¬tions to Prevent Arteriovenous Fistula Failure” were developed through the following five phases. In phase one, a team was established for developing guidelines. In phase two, team members searched published literature before 2018 and identified seventeen related articles. In phase three, the level of evidence according to the 2015 Scottish Intercollegiate Guidelines Network (SIGN) was evaluated. The first draft of the clinical guidelines included 23 items (the scope of the guidelines remaining un¬defined). In phase four, expert validity of the draft was assessed by 10 clinical experts. In phase five, 46 clinicians and 10 hemodialysis patients were invited to evaluate the feasibility of the guidelines, and 21 items were selected for the final version of the guidelines. The clinical care guidelines consist¬ed of 5 constructs with a total of 25 items, including the scope of the guidelines (4 items), pharmaco¬logical treatments for arteriovenous fistula failure (3 items), nursing measures during hemodialysis (6 items), home care measures (4 items), and routine follow-up and management (8 items). With the development of the guidelines, we expect to lower the reconstruction rate of arteriovenous fistula and reduce medical costs through the prevention of arteriovenous fistula failure in hemodialysis patients</p> <p> </p>

Ten-Year Single Center Retrospective Analysis of Adult Native Ankle Joint Septic Arthritis

Septic arthritis (SA) of the native ankle joint can result in serious morbidity and mortality but is a poorly quantified issue with little literature available on its clinical features, treatment and outcomes. This was a 10-y review (N ≥ 30) of adults with SA of the native ankle joint presenting to a single center from December 2009 to January 2019. Patients with prior ankle surgery, prosthetic infection, inoculation from trauma, not initially treated at our institution or lost to follow-up were excluded. Thirty-six patients met inclusion criteria. This is the largest cohort of adult native ankle joint SA in the literature. Mean age was 63.5 y (range 28-93 y). Patients most often presented with pain (91.7%), swelling (61.1%), and fever (22%). Staphylococcus aureus was the most common causative pathogen (63.9%). Readmission rate was 60%. The 1-y mortality rate was 14.3% with Charlson Comorbidity Index and age identified as independent predictors of mortality. No statistically significant predictors were found for returns to theatre. When assessing ankle pain in elderly patients, and those with poor physiology, high clinical index of suspicion should be maintained for this potentially life-threatening condition. We recommend development of evidence-based clinical guidelines for adult native ankle joint SA and establishment of a prospective multi-center database to enable further research in this field.

The PREvention Program for Alzheimer\u2019s RElated Delirium (PREPARED) cluster randomized trial: a study protocol

BackgroundDelirium is a significant cause of morbidity and mortality among older people admitted to both acute and long-term care facilities (LTCFs). Multicomponent interventions have been shown to reduce delirium incidence in the acute care setting (30–73%) by acting on modifiable risk factors. Little work, however, has focused on using this approach to reduce delirium incidence in LTCFs.MethodsThe objective is to assess the effectiveness of the multicomponent PREPARED Trial intervention in reducing the following primary outcomes: incidence, severity, duration, and frequency of delirium episodes in cognitively impaired residents. This 4-year, parallel-design, cluster randomized study will involve nursing staff and residents in 45–50 LTCFs in Montreal, Canada. Participating public and private LTCFs (clusters) that provide 24-h nursing care will be assigned to either the PREPARED Trial intervention or the control (usual care) arm of the study using a covariate constrained randomization procedure. Approximately 400–600 LTC residents aged 65 and older with dementia and/or cognitive impairment will be enrolled in the study and followed for 18 weeks. Residents must be at risk of delirium, delirium-free at baseline and have resided at the facility for at least 2 weeks. Residents who are unable to communicate verbally, have a history of specific psychiatric conditions, or are receiving end-of-life care will be excluded. The PREPARED Trial intervention consists of four main components: a decision tree, an instruction manual, a training package, and a toolkit. Primary study outcomes will be assessed weekly. Functional autonomy and cognitive levels will be assessed at the beginning and end of follow-up, while information pertaining to modifiable delirium risk factors, medical consultations, and facility transfers will be collected retrospectively for the duration of the follow-up period. Primary outcomes will be reported at the level of intervention assignment. All researchers analyzing the data will be blinded to group allocation.DiscussionThis large-scale intervention study will contribute significantly to the development of evidence-based clinical guidelines for delirium prevention in this frail elderly population, as it will be the first to evaluate the efficacy of a multicomponent delirium prevention program translated into LTC clinical practice on a large scale.Trial registrationNCT03718156, ClinicalTrials.gov.

Management of the extraction socket and timing of implant placement: Consensus report and clinical recommendations of group 3 of the XV European Workshop in Periodontology.

The transition from a tooth requiring extraction to its replacement (with a dental implant) requires a series of clinical decisions related to timing, approach, materials, cost-effectiveness and the assessment of potential harm and patient preference. This workshop focused on the formulation of evidence-based consensus statements and clinical recommendations. Four systematic reviews covering the areas of alveolar ridge preservation/bone grafting, immediate early and delayed implant placement and alveolar bone augmentation at the time of implant placement in a healed ridge formed the basis of the deliberations. The level of evidence supporting each consensus statement and its strength was described using a modification of the GRADE tool. The evidence base for each of the relevant topics was assessed and summarized in 23 consensus statements and 12 specific clinical recommendations. The group emphasized that the evidence base mostly relates to single tooth extraction/replacement; hence, external validity/applicability to multiple extractions requires careful consideration. The group identified six considerations that should assist clinicians in clinical decision-making: presence of infection, inability to achieve primary stability in the restoratively driven position, presence of a damaged alveolus, periodontal phenotype, aesthetic demands and systemic conditions. A substantial and expanding evidence base is available to assist clinicians with clinical decision-making related to the transition from a tooth requiring extraction to its replacement with a dental implant. More high-quality research is needed for the development of evidence-based clinical guidelines.

Preoperative repeat endoscopy for colorectal cancer: What is its role and when is it necessary?

Many surgeons consider repeat endoscopy to be the standard of care for colorectal cancer; however, its utility in the preoperative setting is not well understood, especially given the lack of standardized guidelines on appropriate tumour localization and colonoscopic reporting. This often results in patients undergoing an unnecessary medical procedure during their preoperative evaluation. We discuss some of the issues surrounding the practice of preoperative repeat endoscopy as well as patient perspectives on the procedure. Our observations suggest that repeat endoscopy in the setting of colorectal cancer surgery may play a role in enabling transition of patient care between the initial endoscopist and the treating surgeon and in improving the patient experience. Patients with operable colorectal cancer appear to understand and support the current use of repeat endoscopy. However, improving preoperative care will require further research and ultimately the development of evidence-based clinical guidelines.

Application of the STROBE statement to the hypospadias literature: Report of the international pediatric urology task force on hypospadias

Observational studies, particularly case series, represent the majority of the current hypospadias research. As a result, this literature lacks standardization of surgical techniques, uniform definitions of hypospadias complications, and consistency of outcome reporting, which may make it difficult to compare results across studies. A modified version of the STROBE statement, containing 20 items, was presented at the International Pediatric Urology Task Force on Hypospadias meeting to assist with clear and transparent reporting of hypospadias studies. The adoption and implementation of this modified tool will allow investigators and health care providers to critically evaluate quality and identify bias within the literature. In addition this instrument will ensure consistency of reporting, improving objective comparisons between studies, unification of results, and development of evidence-based clinical guidelines. In this article, we have applied the modified STROBE statement to the hypospadias literature, aiming to create a guide on study reporting for pediatric urologists, and ultimately improve the quality of research in our field. We present itemized recommendations for adequate reporting of hypospadias studies and case series, ranging from drafting the abstract to addressing biases and potential sources of confounding. Included with each item is a brief explanation of its importance and potential effect on the study, as well as pertinent examples of hypospadias articles. A modified STROBE summary table containing 20 items is presented in (Supplementary Table 1). If properly conducted and reported, hypospadias studies have the potential to provide useful information to clinicians and surgeons. However, authors should recognize the inherent limitations of these observational studies, especially in the form of bias, which may introduce invalid data or limit generalizability. Thus, we expect that the use of this guiding tool will not only improve transparency of hypospadias reporting, but also improve its methodological quality, allowing proper comparison and interpretation of data across different institutions.

Critical appraisal of AMSTAR: challenges, limitations, and potential solutions from the perspective of an assessor.

BackgroundSystematic reviews are pivotal components in the development of evidence-based clinical guidelines. To evaluate the methodological quality of these systematic reviews, several tools have been proposed. Among them, the assessment of multiple systematic reviews (AMSTAR) checklist is probably used most frequently. This tool comprises 11 items related to the steps taken when conducting a systematic review, and it is claimed to have good face and content validity. The objective of this debate paper was twofold: (a) to critically evaluate the ability of all AMSTAR checklist items to adequately determine the methodological quality of a systematic review; and (b) to describe difficulties regarding interpretation of the checklist, and provide potential solutions for these difficulties.DiscussionSome items of the AMSTAR checklist seem to assess the quality of reporting of a systematic review more than its methodological quality. For example, item 7 may not “capture” the true methodological quality of primary studies included in the systematic review. Item 10 does not likely result in the collection of in-depth information on the presence of publication bias in the systematic review. Furthermore, some items may be difficult to interpret, hindering accurate assessment. For example, item 5 does not explicitly indicate whether a list of documents excluded in each phase of selection (i.e., after evaluation of titles and abstracts, and after full-text assessment) should be reported.SummaryThe present debate paper evaluated and discussed some methodological limitations of the AMSTAR checklist, as well as challenges involved in evaluation of the checklist’s items. Several suggestions are also made to optimize the use of this checklist. The information in this paper may stimulate further discussion among systematic reviewers, methodologists and clinicians.

Perinatal staff perceptions of safety and quality in their service.

BackgroundEnsuring safe and appropriate service delivery is central to a high quality maternity service. With this in mind, over recent years much attention has been given to the development of evidence-based clinical guidelines, staff education and risk reporting systems. Less attention has been given to assessing staff perceptions of a service’s safety and quality and what factors may influence that. In this study we set out to assess staff perceptions of safety and quality of a maternity service and to explore potential influences on service safety.MethodsThe study was undertaken within a new low risk metropolitan maternity service in Victoria, Australia with a staffing profile comprising midwives (including students), neonatal nurses, specialist obstetricians, junior medical staff and clerical staff. In depth open-ended interviews using a semi-structured questionnaire were conducted with 23 staff involved in the delivery of perinatal care, including doctors, midwives, nurses, nursing and midwifery students, and clerical staff. Data were analyzed using naturalistic interpretive inquiry to identify emergent themes.ResultsStaff unanimously reported that there were robust systems and processes in place to maintain safety and quality. Three major themes were apparent: (1) clinical governance, (2) dominance of midwives, (3) inter-professional relationships. Overall, there was a strong sense that, at least in this midwifery-led service, midwives had the greatest opportunity to be an influence, both positively and negatively, on the safe delivery of perinatal care. The importance of understanding team dynamics, particularly mutual respect, trust and staff cohesion, were identified as key issues for potential future service improvement.ConclusionsSenior staff, particularly midwives and neonatal nurses, play central roles in shaping team behaviors and attitudes that may affect the safety and quality of service delivery. We suggest that strategies targeting senior staff to enhance their performance in their roles, particularly in the training and teamwork role-modeling of the transitory junior workforce, are important for the development and maintenance of a high quality and safe maternity service.

Cervico-vaginopathogenic Escherichia coli in Iran: Serogroup distributions, virulence factors and antimicrobial resistance properties

Escherichia coli (E. coli) play an important role in urogenital infection in pregnant and non-pregnant women. They are classified based on various types of O antigen, virulence properties, phylogenetic background and antimicrobial susceptibility pattern. E. coli strains that cause genitourinary infections possess several genes encoding urogenito-virulent factors. The aim of the present study was to determine the prevalence of eight known urovirulence factors and its association with serotypes, phylogenetic background and antimicrobial susceptibility pattern. One hundred thirty two cervico-vaginal E. coli (CVEC) isolates from pregnant and non-pregnant women (18–55 years old) were surveyed for adhesins (fimH, iha), haemolysins (hlyA), outer membrane protease (ompT) and siderophore receptors (irp2, iroN and iucD), cytotoxic necrotizing factor 1 (cnf1), and 12 selected O serotypes by multiplex-PCR. E. coli isolates were classified into intraspecies phylogenetic groups by PCR amplifications of phylogenetic markers. Antimicrobial susceptibility was determined by Kirby–Bauer's disc diffusion method. The most frequently found virulence factor-encoding gene, in descending order were: fimH (71%), irp2 (63%), followed by ompT (45%), iucD (37%), and iroN (31%) genes. The most prevalent serogroups for all E. coli isolates were O25, O15 and O6. There was an acceptable correlation between serotype and genotype in CVEC. The most isolated strains belonged to the phylogenetic group B2, harboring all tested virulence genes. Resistance to ampicillin was most frequently observed, followed by resistance to amikacin and cefazolin. The results suggest that E. coli isolates from different infection origins may have different characteristics. A better understanding of these differences may lead to further development of evidence-based clinical guidelines for the management of cervico-vaginal infection.

The Moldovan experience of maternal death reviews.

A Confidential Enquiry into Maternal Deaths is an anonymous, multidisciplinary and systematic review of all cases of maternal mortality. This paper describes one such process implemented at national level in Moldova. Its aim was to conduct an in-depth review of the underlying causes and circumstances surrounding each mother's death to learn lessons to improve care in future. Its findings showed that deaths were predominantly due to direct obstetric causes, especially haemorrhage and sepsis, and adverse social determinants, particularly poverty and migration also played a decisive role in more than half of the cases. The final report identified potentially remediable actions and the key areas requiring interventions by the health sector, administrators and the community. Its recommendations have enabled the implementation of some solutions to help prevent future maternal deaths, including the development of evidence-based clinical guidelines.

The development of chronic cough in children following presentation to a tertiary paediatric emergency department with acute respiratory illness: study protocol for a prospective cohort study

BackgroundAcute respiratory illness, a leading cause of cough in children, accounts for a substantial proportion of childhood morbidity and mortality worldwide. In some children acute cough progresses to chronic cough (>4 weeks duration), impacting on morbidity and decreasing quality of life. Despite the importance of chronic cough as a cause of substantial childhood morbidity and associated economic, family and social costs, data on the prevalence, predictors, aetiology and natural history of the symptom are scarce. This study aims to comprehensively describe the epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children presenting to a tertiary paediatric emergency department.Methods/designA prospective cohort study of children aged <15 years attending the Royal Children’s Hospital Emergency Department, Brisbane, for a respiratory illness that includes parent reported cough (wet or dry) as a symptom. The primary objective is to determine the prevalence and predictors of chronic cough (≥4 weeks duration) post presentation with acute respiratory illness. Demographic, epidemiological, risk factor, microbiological and clinical data are completed at enrolment. Subjects complete daily cough dairies and weekly follow-up contacts for 28(±3) days to ascertain cough persistence. Children who continue to cough for 28 days post enrolment are referred to a paediatric respiratory physician for review. Primary analysis will be the proportion of children with persistent cough at day 28(±3). Multivariate analyses will be performed to evaluate variables independently associated with chronic cough at day 28(±3).DiscussionOur protocol will be the first to comprehensively describe the natural history, epidemiology, aetiology and outcomes of cough during and after acute respiratory illness in children. The results will contribute to studies leading to the development of evidence-based clinical guidelines to improve the early detection and management of chronic cough in children during and after acute respiratory illness.

Cross-sectional survey of meticillin-resistant Staphylococcus aureus home-based decolonization practices in Scotland

Despite limited evidence of meticillin-resistant Staphylococcus aureus (MRSA) decolonization efficacy, the practice of decolonization for both pre-admission and on-admission patients is growing. Recent research within National Health Service (NHS) Scotland revealed low rates of treatment and consequent low efficacy in home-based decolonization. As no national guidelines on home-based decolonization currently exist, practices within NHS Scotland may be variable. To establish current pre-admission MRSA home-based decolonization protocols and patient advice within NHS Scotland. Similarities and differences were identified to determine possible sources of variability. Cross-sectional survey distributed electronically to MRSA Screening Project Managers within each NHS geographical region in Scotland (N = 15). Thirteen out of 15 NHS regions responded; one region reported no standard protocol. From the remaining 12 regions, 100% recommended use of mupirocin and antiseptic bodywash daily for five days; this was the only consistent aspect of practice across responding regions. Variation was noted in advice regarding method of mupirocin application, bodywash product and volume of bodywash recommended. Six regions (50%) specified bodywash skin contact time, yet these times varied across regions. Mouth care was advocated by three regions (25%). Daily change of facecloths and clothes was endorsed by five regions (41.7%); four regions (33.3%) promoted daily towel changes. Only one region (8.3%) suggested daily bedroom cleaning; three regions (25%) advised changing bed linen daily. Variation in protocols and patient advice may influence efficacy of home-based decolonization and further research may inform the development of evidence-based clinical guidelines.

Need for early recognition and therapeutic guidelines of congenital sideroblastic anaemia

We present a patient with iron overload, who was initially diagnosed with hereditary haemochromatosis. Family analysis, however, established that the iron overload was secondary to congenital sideroblastic anaemia. The patient died of a hepatocellular carcinoma, likely a complication of iron overload, despite phlebotomies. Increased awareness, as well as development of evidence-based clinical guidelines, is required for timely diagnosis and adequate treatment.

Management of drooling in children: a survey of UK paediatricians' clinical practice

Drooling is common in children with disordered oral-motor control. There is little evidence about the comparative effectiveness of different interventions used to reduce the impact of drooling. Anecdotal reports suggest clinicians' management of drooling varies widely. The aims of this survey were to establish which drooling interventions are currently used, how their effectiveness is monitored and how frequently adverse effects are reported. 151 UK paediatricians completed a questionnaire about their management of drooling. Paediatricians saw one new child with problematic drooling and three follow-up children per month. The most common prescribing pattern was hyoscine first line (84.7%) followed by glycopyrronium bromide second line. The reported rate of adverse effects of medications was lower than expected (median 10% for hyoscine). Very few paediatricians used standardized methods of measuring the medication's effectiveness or adverse effects. Paediatricians regularly see small numbers of children with problematic drooling. Their clinical management of drooling varies; this is most likely because of a lack of evidence about the most effective approach. Comparative trials of interventions and the development of evidence-based clinical guidelines would improve the management of children's drooling.

A questionnaire survey of UK physiotherapists on the diagnosis and management of contracted (frozen) shoulder

Objective To gain insights into the diagnosis and management of contracted (frozen) shoulder (CFS) in a sample of UK physiotherapists, underpinning the development of evidence-based clinical guidelines. Methods An anonymous online questionnaire was developed and distributed via iCSP, targeting physiotherapists who treat CFS. For treatments, respondents were invited to consider ‘pain-predominant’ and ‘stiffness-predominant’ scenarios, choose from listed treatment options, and specify any unlisted conservative options they might consider. Frequency analysis was used for closed-ended questions, and content analysis was used for open-ended questions. Results In total, 289 valid responses were received. All respondents thought that movement restriction informed diagnosis. Of those specifying the manner of testing movements, 98% (121/123) included passive testing. Of those describing specific patterns of restriction, 71% (93/131) emphasised external rotation. Fifty-four percent (152/282) of valid respondents would consider suggesting/requesting imaging investigations, usually to exclude bony abnormalities. For treatment, only 46 respondents reported considering any unlisted conservative options, usually liaison regarding medication. For pain-predominant CFS, the preferred physiotherapeutic options were advice/education (96%; 277/288), injection (80%; 230/288), gentle exercise (79%; 228/288), superficial heat/cold (69%; 199/288) and acupuncture (68%; 196/288). For stiffness-predominant CFS, the preferred options were stretching (93%; 268/288), advice/education (88%; 252/288), joint mobilisations (87%; 250/288), function-based exercises (75%; 216/288) and hands-on soft-tissue techniques (59%; 170/288). Some dissociation was noted between clinical practice and research evidence. Eighty-five percent (253/284) of respondents would consider referring for an orthopaedic opinion. Conclusions Acknowledging restricted passive external rotation (vs the capsular pattern) as diagnostic of CFS would standardise and might improve the clinical aspect of diagnosis. The value of X-rays in differential diagnosis was under-recognised. Modalities used to treat CFS were dichotomised by pain-predominant and stiffness-predominant classifications, which may be more useful than existing classifications.

Comparison of virulence factors in Pseudomonas aeruginosa strains isolated from contact lens- and non-contact lens-related keratitis

Pseudomonas aeruginosa is one of the common pathogens associated with corneal infection, particularly in contact lens-related keratitis events. The pathogenesis of P. aeruginosa in keratitis is attributed to the production of virulence factors under certain environmental conditions. The aim of this study was to determine differences in the virulence factors of P. aeruginosa isolated from contact lens- and non-contact lens-related keratitis. Associations were assessed between type III secretion toxin-encoding genes, protease profiles, biofilm formation, serotypes and antibiotic-resistance patterns among 27 non-contact lens- and 28 contact lens-related P. aeruginosa keratitis isolates from Australia. Strains with a exoS+/exoU- genotype and a type I protease profile predominated in the non-contact lens-related keratitis isolates, whereas the exoS-/exoU+ and a type II protease profile was associated with contact lens-related isolates (P<0.05). A strong biofilm formation phenotype was found to be associated with the possession of the exoU gene, and serotypes E, I and C. The exoS gene was strongly associated with serotypes G, A and B, while exoU was associated with serotypes E and C. Six out of fifty-five (11 %) clinical isolates were non-susceptible (intermediate-resistant or resistant) to ofloxacin and moxifloxacin. All resistant isolates were from non-contact lens-related keratitis. The results suggest that P. aeruginosa isolates from different infection origins may have different characteristics. A better understanding of these differences may lead to further development of evidence-based clinical guidelines for the management of keratitis.

The Health Benefits Of Genomics: Out With The Old, In With The New

The disproportionate emphasis on discovery research in genetics and genomics needs to be balanced by new approaches to funding translational research, development of evidence-based clinical guidelines, and robust regulation of genetic tests. These measures will help ensure that patients, providers, and others are better able to discriminate between valid genomic applications that can improve public health and those that are not useful and potentially harmful. Doing so will require that we dispense with models of research support and regulatory guidance designed for the pre-Human Genome Project world, and replace them with policies and programs as innovative as genetics research itself has been.