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1.  Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain 
Background
Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients.
Methods
Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools.
Results
The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools.
Conclusions
Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.
doi:10.1186/1748-5908-5-26
PMCID: PMC2868045  PMID: 20385018
2.  Evaluation of Internet-Based Clinical Decision Support Systems 
Background
Scientifically based clinical guidelines have become increasingly used to educate physicians and improve quality of care. While individual guidelines are potentially useful, repeated studies have shown that guidelines are ineffective in changing physician behavior. The Internet has evolved as a potentially useful tool for guideline education, dissemination, and implementation because of its open standards and its ability to provide concise, relevant clinical information at the location and time of need.
Objective
Our objective was to develop and test decision support systems (DSS) based on clinical guidelines which could be delivered over the Internet for two disease models: asthma and tuberculosis (TB) preventive therapy.
Methods
Using open standards of HTML and CGI, we developed an acute asthma severity assessment DSS and a preventative tuberculosis treatment DSS based on content from national guidelines that are recognized as standards of care. Both DSS's are published on the Internet and operate through a decision algorithm developed from the parent guidelines with clinical information provided by the user at the point of clinical care. We tested the effectiveness of each DSS in influencing physician decisions using clinical scenario testing.
Results
We first validated the asthma algorithm by comparing asthma experts' decisions with the decisions reached by nonpulmonary nurses using the computerized DSS. Using the DSS, nurses scored the same as experts (89% vs. 88%; p = NS). Using the same scenario test instrument, we next compared internal medicine residents using the DSS with residents using a printed version of the National Asthma Education Program-2 guidelines. Residents using the computerized DSS scored significantly better than residents using the paper-based guidelines (92% vs. 84%; p <0.002). We similarly compared residents using the computerized TB DSS to residents using a printed reference card; the residents using the computerized DSS scored significantly better (95.8% vs. 56.6% correct; p<0.001).
Conclusions
Previous work has shown that guidelines disseminated through traditional educational interventions have minimal impact on physician behavior. Although computerized DSS have been effective in altering physician behavior, many of these systems are not widely available. We have developed two clinical DSS's based on national guidelines and published them on the Internet. Both systems improved physician compliance with national guidelines when tested in clinical scenarios. By providing information that is coupled to relevant activity, we expect that these widely available DSS's will serve as effective educational tools to positively impact physician behavior.
doi:10.2196/jmir.1.2.e6
PMCID: PMC1761710  PMID: 11720915
Asthma; Tuberculosis; Decision Support System; Clinical Guidelines
3.  Knowledge of antibiotics among dentists in Riyadh private clinics 
The Saudi Dental Journal  2013;25(3):119-124.
Introduction
Dentists prescribe antibiotics for both therapeutic and prophylactic reasons to manage oral and dental infections. Antibiotic prescriptions can be associated with unfavorable side effects and the development of resistance.
Aim of the study
A survey was conducted among dental specialists (DSs) and general dental practitioners (GDPs) at private dental clinics in Riyadh, Saudi Arabia to assess their level of knowledge regarding the action of antibiotics, their use and misuse in oral conditions, systemic diseases and prophylaxis.
Subjects and methods
A total of 380 identical surveys that contained 32 questions were completed by DSs and GDPs in a supervised setting. Descriptive statistics were calculated to assess the overall knowledge of both DSs and GDPs, and their knowledge within each category of questions. Independent t-tests were used to ascertain whether there were significant differences between DSs and GDPs. A scatterplot diagram was used to test for a correlation between the years of experience of practitioners and their knowledge level.
Result
The response rate was 79.7%. An acceptable level of knowledge was attained by 85.5% of dentists and 42.2% just passed. The percentage of dentists with an acceptable level of knowledge regarding prophylaxis was 51%. The scores for overall information levels about antibiotics among both DSs and GDPs were close to 70%. The percentage of DSs with an acceptable level of knowledge on antibiotic actions was 69.2%, 90.7% for oral conditions and 66.7% for medical conditions, compared to 66.8%, 88.7% and 64.8%, respectively, for GDPs. No significant relationship was found between the experience and knowledge level.
Conclusions
Our findings suggest that the overall knowledge level of dentists about antibiotics is acceptable, but more focus should be given to their ongoing training regarding the pharmacological aspects, pertinent medical conditions and prophylactic use of antibiotics.
doi:10.1016/j.sdentj.2013.05.001
PMCID: PMC3809504  PMID: 24179321
Dentists; Antibiotics’ knowledge; Antibiotics; Riyadh dental private clinics
4.  Evaluation of computerized decision support for oral anticoagulation management based in primary care. 
BACKGROUND: Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. AIM: To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). METHOD: All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. RESULTS: Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. CONCLUSION: Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.
PMCID: PMC1239749  PMID: 8917873
5.  Rational Prescribing in Primary Care (RaPP): A Cluster Randomized Trial of a Tailored Intervention 
PLoS Medicine  2006;3(6):e134.
Background
A gap exists between evidence and practice regarding the management of cardiovascular risk factors. This gap could be narrowed if systematically developed clinical practice guidelines were effectively implemented in clinical practice. We evaluated the effects of a tailored intervention to support the implementation of systematically developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease.
Methods and Findings
We conducted a cluster-randomized trial comparing a tailored intervention to passive dissemination of guidelines in 146 general practices in two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Patients started on medication for hypertension or hypercholesterolemia during the study period and all patients already on treatment that consulted their physician during the trial were included. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders linked to the medical record system. Pharmacists conducted the visits. Outcomes were measured for all eligible patients seen in the participating practices during 1 y before and after the intervention. The main outcomes were the proportions of (1) first-time prescriptions for hypertension where thiazides were prescribed, (2) patients assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs, and (3) patients treated for hypertension or hypercholesterolemia for 3 mo or more who had achieved recommended treatment goals.
The intervention led to an increase in adherence to guideline recommendations on choice of antihypertensive drug. Thiazides were prescribed to 17% of patients in the intervention group versus 11% in the control group (relative risk 1.94; 95% confidence interval 1.49–2.49, adjusted for baseline differences and clustering effect). Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.
Conclusions
Our tailored intervention had a significant impact on prescribing of antihypertensive drugs, but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care.
Editors' Summary
Background.
An important issue in health care is “getting research into practice,” in other words, making sure that, when evidence from research has established the best way to treat a disease, doctors actually use that approach with their patients. In reality, there is often a gap between evidence and practice.
  An example concerns the treatment of people who have high blood pressure (hypertension) and/or high cholesterol. These are common conditions, and both increase the risk of having a heart attack or a stroke. Research has shown that the risks can be lowered if patients with these conditions are given drugs that lower blood pressure (antihypertensives) and drugs that lower cholesterol. There are many types of these drugs now available. In many countries, the health authorities want family doctors (general practitioners) to make better use of these drugs. They want doctors to prescribe them to everyone who would benefit, using the type of drugs found to be most effective. When there is a choice of drugs that are equally effective, they want doctors to use the cheapest type. (In the case of antihypertensives, an older type, known as thiazides, is very effective and also very cheap, but many doctors prefer to give their patients newer, more expensive alternatives.) Health authorities have issued guidelines to doctors that address these issues. However, it is not easy to change prescribing practices, and research in several countries has shown that issuing guidelines has only limited effects.
Why Was This Study Done?
The researchers wanted—in two parts of Norway—to compare the effects on prescribing practices of what they called the “passive dissemination of guidelines” with a more active approach, where the use of the guidelines was strongly promoted and encouraged.
What Did the Researchers Do and Find?
They worked with 146 general practices. In half of them the guidelines were actively promoted. The remaining were regarded as a control group; they were given the guidelines but no special efforts were made to encourage their use. It was decided at random which practices would be in which group; this approach is called a randomized controlled trial. The methods used to actively promote use of the guidelines included personal visits to the practices by pharmacists and use of a computerized reminder system. Information was then collected on the number of patients who, when first treated for hypertension, were prescribed a thiazide. Other information collected included whether patients had been properly assessed for their level of risk (for strokes and heart attacks) before antihypertensive or cholesterol-lowering drugs were given. In addition, the researchers recorded whether the recommended targets for improvement in blood pressure and cholesterol level had been reached.
Only 11% of those patients visiting the control group of practices who should have been prescribed thiazides, according to the guidelines, actually received them. Of those seen by doctors in the practices where the guidelines were actively promoted, 17% received thiazides. According to statistical analysis, the increase achieved by active promotion is significant. Little or no differences were found for risk assessment prior to prescribing and for achievement of treatment goals.
What Do These Findings Mean?
Even in the active promotion group, the great majority of patients (83%) were still not receiving treatment according to the guidelines. However, active promotion of guidelines is more effective than simply issuing the guidelines by themselves. The study also demonstrates that it is very hard to change prescribing practices. The efforts made here to encourage the doctors to change were considerable, and although the results were significant, they were still disappointing. Also disappointing is the fact that achievement of treatment goals was no better in the active-promotion group. These issues are discussed further in a Perspective about this study (DOI: 10.1371/journal.pmed.0030229).
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030134.
• The Web site of the American Academy of Family Physicians has a page on heart disease
• The MedlinePlus Medical Encyclopedia's pages on heart diseases and vascular diseases
• Information from NHS Direct (UK National Health Service) about heart attack and stroke
• Another PLoS Medicine article has also addressed trends in thiazide prescribing
Passive dissemination of management guidelines for hypertension and hypercholesterolaemia was compared with active promotion. Active promotion led to significant improvement in antihypertensive prescribing but not other aspects of management.
doi:10.1371/journal.pmed.0030134
PMCID: PMC1472695  PMID: 16737346
6.  Development and Validation of a Clinical and Computerised Decision Support System for Management of Hypertension (DSS-HTN) at a Primary Health Care (PHC) Setting 
PLoS ONE  2013;8(11):e79638.
Background
Hypertension remains the top global cause of disease burden. Decision support systems (DSS) could provide an adequate and cost-effective means to improve the management of hypertension at a primary health care (PHC) level in a developing country, nevertheless evidence on this regard is rather limited.
Methods
Development of DSS software was based on an algorithmic approach for (a) evaluation of a hypertensive patient, (b) risk stratification (c) drug management and (d) lifestyle interventions, based on Indian guidelines for hypertension II (2007). The beta testing of DSS software involved a feedback from the end users of the system on the contents of the user interface. Software validation and piloting was done in field, wherein the virtual recommendations and advice given by the DSS were compared with two independent experts (government doctors from the non-participating PHC centers).
Results
The overall percent agreement between the DSS and independent experts among 60 hypertensives on drug management was 85% (95% CI: 83.61 - 85.25). The kappa statistic for overall agreement for drug management was 0.659 (95% CI: 0.457 - 0.862) indicating a substantial degree of agreement beyond chance at an alpha fixed at 0.05 with 80% power. Receiver operator curve (ROC) showed a good accuracy for the DSS, wherein, the area under curve (AUC) was 0.848 (95% CI: 0.741 - 0.948). Sensitivity and specificity of the DSS were 83.33 and 85.71% respectively when compared with independent experts.
Conclusion
A point of care, pilot tested and validated DSS for management of hypertension has been developed in a resource constrained low and middle income setting and could contribute to improved management of hypertension at a primary health care level.
doi:10.1371/journal.pone.0079638
PMCID: PMC3818237  PMID: 24223984
7.  Decision tools in health care: focus on the problem, not the solution 
Background
Systematic reviews or randomised-controlled trials usually help to establish the effectiveness of drugs and other health technologies, but are rarely sufficient by themselves to ensure actual clinical use of the technology. The process from innovation to routine clinical use is complex. Numerous computerised decision support systems (DSS) have been developed, but many fail to be taken up into actual use. Some developers construct technologically advanced systems with little relevance to the real world. Others did not determine whether a clinical need exists. With NHS investing £5 billion in computer systems, also occurring in other countries, there is an urgent need to shift from a technology-driven approach to one that identifies and employs the most cost-effective method to manage knowledge, regardless of the technology. The generic term, 'decision tool' (DT), is therefore suggested to demonstrate that these aids, which seem different technically, are conceptually the same from a clinical viewpoint.
Discussion
Many computerised DSSs failed for various reasons, for example, they were not based on best available knowledge; there was insufficient emphasis on their need for high quality clinical data; their development was technology-led; or evaluation methods were misapplied. We argue that DSSs and other computer-based, paper-based and even mechanical decision aids are members of a wider family of decision tools. A DT is an active knowledge resource that uses patient data to generate case specific advice, which supports decision making about individual patients by health professionals, the patients themselves or others concerned about them. The identification of DTs as a consistent and important category of health technology should encourage the sharing of lessons between DT developers and users and reduce the frequency of decision tool projects focusing only on technology. The focus of evaluation should become more clinical, with the impact of computer-based DTs being evaluated against other computer, paper- or mechanical tools, to identify the most cost effective tool for each clinical problem.
Summary
We suggested the generic term 'decision tool' to demonstrate that decision-making aids, such as computerised DSSs, paper algorithms, and reminders are conceptually the same, so the methods to evaluate them should be the same.
doi:10.1186/1472-6947-6-4
PMCID: PMC1397808  PMID: 16426446
8.  Handheld Computer-based Decision Support Reduces Patient Length of Stay and Antibiotic Prescribing in Critical Care 
Objective: This study assessed the effect of a handheld computer-based decision support system (DSS) on antibiotic use and patient outcomes in a critical care unit.
Design: A DSS containing four types of evidence (patient microbiology reports, local antibiotic guidelines, unit-specific antibiotic susceptibility data for common bacterial pathogens, and a clinical pulmonary infection score calculator) was developed and implemented on a handheld computer for use in the intensive care unit at a tertiary referral hospital. System impact was assessed in a prospective “before/after” cohort trial lasting 12 months. Outcome measures were defined daily doses (DDDs) of antibiotics per 1,000 patient-days, patient length of stay, and mortality.
Results: The number of admissions, APACHE (Acute Physiology, Age, and Chronic Health Evaluation) II and SAPS (Simplified Acute Physiology Score) II for patients in preintervention, and intervention (DSS use) periods were statistically comparable. The mean patient length of stay and the use of antibiotics in the unit during six months of the DSS use decreased from 7.15 to 6.22 bed-days (p = 0.02) and from 1,767 DDD to 1,458 DDD per 1,000 patient-days (p = 0.04), respectively, with no change in mortality. The DSS was accessed 674 times during 168 days of the trial. Microbiology reports and antibiotic guidelines were the two most commonly used (53% and 22.5%, respectively) types of evidence. The greatest reduction was observed in the use of β-lactamase–resistant penicillins and vancomycin.
Conclusion: Handheld computer-based decision support contributed to a significant reduction in patient length of stay and antibiotic prescribing in a critical care unit.
doi:10.1197/jamia.M1798
PMCID: PMC1174884  PMID: 15802478
9.  Comparative Impact of Guidelines, Clinical Data, and Decision Support on Prescribing Decisions: An Interactive Web Experiment with Simulated Cases 
Objective: The aim of this study was to compare the clinical impact of computerized decision support with and without electronic access to clinical guidelines and laboratory data on antibiotic prescribing decisions.
Design: A crossover trial was conducted of four levels of computerized decision support—no support, antibiotic guidelines, laboratory reports, and laboratory reports plus a decision support system (DSS), randomly allocated to eight simulated clinical cases accessed by the Web.
Measurements Rate of intervention adoption was measured by frequency of accessing information support, cost of use was measured by time taken to complete each case, and effectiveness of decision was measured by correctness of and self-reported confidence in individual prescribing decisions. Clinical impact score was measured by adoption rate and decision effectiveness.
Results Thirty-one intensive care and infectious disease specialist physicians (ICPs and IDPs) participated in the study. Ventilator-associated pneumonia treatment guidelines were used in 24 (39%) of the 62 case scenarios for which they were available, microbiology reports in 36 (58%), and the DSS in 37 (60%). The use of all forms of information support did not affect clinicians' confidence in their decisions. Their use of the DSS plus microbiology report improved the agreement of decisions with those of an expert panel from 65% to 97% (p = 0.0002), or to 67% (p = 0.002) when antibiotic guidelines only were accessed. Significantly fewer IDPs than ICPs accessed information support in making treatment decisions. On average, it took 245 seconds to make a decision using the DSS compared with 113 seconds for unaided prescribing (p < 0.001). The DSS plus microbiology reports had the highest clinical impact score (0.58), greater than that of electronic guidelines (0.26) and electronic laboratory reports (0.45).
Conclusion: When used, computer-based decision support significantly improved decision quality. In measuring the impact of decision support systems, both their effectiveness in improving decisions and their likely rate of adoption in the clinical environment need to be considered. Clinicians chose to use antibiotic guidelines for one third and microbiology reports or the DSS for about two thirds of cases when they were available to assist their prescribing decisions.
doi:10.1197/jamia.M1166
PMCID: PMC305460  PMID: 14527970
10.  Reviewing the development, evidence base, and application of the revised dengue case classification 
Pathogens and Global Health  2012;106(2):94-101.
With the example of dengue, an evidence-based approach to prospectively develop a case classification is described, gathering evidence for identifying strength and weaknesses of the existing model, collecting new data describing the disease as it occurs globally, further developing a new model that can be applied in practice and field testing the newly developed model in comparison to the previous model. For each step in this process, the highest available level of evidence has been applied. This process has been initiated by the World Health Organization’s (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) and WHO’s Department for Control of Neglected Tropical Diseases (NTD), developing the following for dengue. Since the early 1970s, dengue has been classified into dengue fever, dengue haemorrhagic fever grades I and II and dengue shock syndrome grades III and IV (DF/DHF/DSS). However, in recent years, a growing number of dengue clinicians have questioned the shortcomings of this scheme. The issues have revolved around the complexity of confirming DHF in clinical practice, misclassifying severe cases as DF, and the emphasis on haemorrhage rather than plasma leakage as the underlying problem in most severe dengue cases. Step 1: A systematic literature review highlighted the shortcomings of the DF/DHF/DSS scheme: (1) difficulties in applying the criteria for DHF/DSS; (2) the tourniquet test has a low sensitivity for distinguishing between DHF and DF; and (3) most DHF criteria had a large variability in frequency of occurrence. Step 2: An analysis of regional and national dengue guidelines and their application in the clinical practice showed a need to re-evaluate and standardize guidelines as the actual ones showed a large variation of definitions, an inconsistent application by medical staff, and a lack of diagnostic facilities necessary for the DHF diagnosis in frontline services. Step 3: A prospective cohort study in seven countries, confirmed the difficulties in applying the DF/DHF/DSS criteria even in tertiary care hospitals, that DF/DHF/DSS do not represent levels of disease severity and that a clear distinction between severe dengue (defined by plasma leakage and/or severe haemorrhage, and/or organ failure) and (non-severe) dengue can be made using highly sensitive and specific criteria. In contrast, the sub-grouping of (non-severe) dengue into two further severity levels was only possible with criteria that gave approximately 70% sensitivity and specificity. Step 4: Three regional expert consensus groups in the Americas and Asia concluded that ‘dengue is one disease entity with different clinical presentations and often with unpredictable clinical evolution and outcome’ and that, revising the results of Step 3, DF/DHF/DSS is not related to disease severity. Step 5: In a global expert consensus meeting at WHO in Geneva/Switzerland the evidence collected in Steps 1–4 was reviewed and a revised scheme was developed and accepted, distinguishing: dengue with or without warning signs and severe dengue; the further field testing and acquisition of further prospective evidence of the revised scheme was recommended. Step 6: In 18 countries, the usefulness and applicability of the revised classification compared to the DF/DHF/DSS scheme were tested showing clear results in favour of the revised classification. Step 7: Studies are under way on the predictive value of warning signs for severe dengue and on criteria for the clinical diagnosis of dengue which will complete the evidence foundation of the revised classification. The analysis has shown that the revised dengue case classification is better able to standardize clinical management, raise awareness about unnecessary interventions, match patient categories with specific treatment instructions, and make the key messages of patient management understandable for all health care staff dealing with dengue patients. Furthermore, the evidence-based approach to develop prospectively the dengue case classification could be a model approach for other disease classifications.
doi:10.1179/2047773212Y.0000000017
PMCID: PMC3408880  PMID: 22943544
Dengue; Case classification; Evidence-based approaches
11.  Information from Pharmaceutical Companies and the Quality, Quantity, and Cost of Physicians' Prescribing: A Systematic Review 
PLoS Medicine  2010;7(10):e1000352.
Geoff Spurling and colleagues report findings of a systematic review looking at the relationship between exposure to promotional material from pharmaceutical companies and the quality, quantity, and cost of prescribing. They fail to find evidence of improvements in prescribing after exposure, and find some evidence of an association with higher prescribing frequency, higher costs, or lower prescribing quality.
Background
Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing.
Methods and Findings
We searched for studies of physicians with prescribing rights who were exposed to information from pharmaceutical companies (promotional or otherwise). Exposures included pharmaceutical sales representative visits, journal advertisements, attendance at pharmaceutical sponsored meetings, mailed information, prescribing software, and participation in sponsored clinical trials. The outcomes measured were quality, quantity, and cost of physicians' prescribing. We searched Medline (1966 to February 2008), International Pharmaceutical Abstracts (1970 to February 2008), Embase (1997 to February 2008), Current Contents (2001 to 2008), and Central (The Cochrane Library Issue 3, 2007) using the search terms developed with an expert librarian. Additionally, we reviewed reference lists and contacted experts and pharmaceutical companies for information. Randomized and observational studies evaluating information from pharmaceutical companies and measures of physicians' prescribing were independently appraised for methodological quality by two authors. Studies were excluded where insufficient study information precluded appraisal. The full text of 255 articles was retrieved from electronic databases (7,185 studies) and other sources (138 studies). Articles were then excluded because they did not fulfil inclusion criteria (179) or quality appraisal criteria (18), leaving 58 included studies with 87 distinct analyses. Data were extracted independently by two authors and a narrative synthesis performed following the MOOSE guidelines. Of the set of studies examining prescribing quality outcomes, five found associations between exposure to pharmaceutical company information and lower quality prescribing, four did not detect an association, and one found associations with lower and higher quality prescribing. 38 included studies found associations between exposure and higher frequency of prescribing and 13 did not detect an association. Five included studies found evidence for association with higher costs, four found no association, and one found an association with lower costs. The narrative synthesis finding of variable results was supported by a meta-analysis of studies of prescribing frequency that found significant heterogeneity. The observational nature of most included studies is the main limitation of this review.
Conclusions
With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
A prescription drug is a medication that can be supplied only with a written instruction (“prescription”) from a physician or other licensed healthcare professional. In 2009, 3.9 billion drug prescriptions were dispensed in the US alone and US pharmaceutical companies made US$300 billion in sales revenue. Every year, a large proportion of this revenue is spent on drug promotion. In 2004, for example, a quarter of US drug revenue was spent on pharmaceutical promotion. The pharmaceutical industry claims that drug promotion—visits from pharmaceutical sales representatives, advertisements in journals and prescribing software, sponsorship of meetings, mailed information—helps to inform and educate healthcare professionals about the risks and benefits of their products and thereby ensures that patients receive the best possible care. Physicians, however, hold a wide range of views about pharmaceutical promotion. Some see it as a useful and convenient source of information. Others deny that they are influenced by pharmaceutical company promotion but claim that it influences other physicians. Meanwhile, several professional organizations have called for tighter control of promotional activities because of fears that pharmaceutical promotion might encourage physicians to prescribe inappropriate or needlessly expensive drugs.
Why Was This Study Done?
But is there any evidence that pharmaceutical promotion adversely influences prescribing? Reviews of the research literature undertaken in 2000 and 2005 provide some evidence that drug promotion influences prescribing behavior. However, these reviews only partly assessed the relationship between information from pharmaceutical companies and prescribing costs and quality and are now out of date. In this study, therefore, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) to reexamine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing.
What Did the Researchers Do and Find?
The researchers searched the literature for studies of licensed physicians who were exposed to promotional and other information from pharmaceutical companies. They identified 58 studies that included a measure of exposure to any type of information directly provided by pharmaceutical companies and a measure of physicians' prescribing behavior. They then undertook a “narrative synthesis,” a descriptive analysis of the data in these studies. Ten of the studies, they report, examined the relationship between exposure to pharmaceutical company information and prescribing quality (as judged, for example, by physician drug choices in response to clinical vignettes). All but one of these studies suggested that exposure to drug company information was associated with lower prescribing quality or no association was detected. In the 51 studies that examined the relationship between exposure to drug company information and prescribing frequency, exposure to information was associated with more frequent prescribing or no association was detected. Thus, for example, 17 out of 29 studies of the effect of pharmaceutical sales representatives' visits found an association between visits and increased prescribing; none found an association with less frequent prescribing. Finally, eight studies examined the relationship between exposure to pharmaceutical company information and prescribing costs. With one exception, these studies indicated that exposure to information was associated with a higher cost of prescribing or no association was detected. So, for example, one study found that physicians with low prescribing costs were more likely to have rarely or never read promotional mail or journal advertisements from pharmaceutical companies than physicians with high prescribing costs.
What Do These Findings Mean?
With rare exceptions, these findings suggest that exposure to pharmaceutical company information is associated with either no effect on physicians' prescribing behavior or with adverse affects (reduced quality, increased frequency, or increased costs). Because most of the studies included in the review were observational studies—the physicians in the studies were not randomly selected to receive or not receive drug company information—it is not possible to conclude that exposure to information actually causes any changes in physician behavior. Furthermore, although these findings provide no evidence for any net improvement in prescribing after exposure to pharmaceutical company information, the researchers note that it would be wrong to conclude that improvements do not sometimes happen. The findings support the case for reforms to reduce negative influence to prescribing from pharmaceutical promotion.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000352.
Wikipedia has pages on prescription drugs and on pharmaceutical marketing (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The UK General Medical Council provides guidelines on good practice in prescribing medicines
The US Food and Drug Administration provides information on prescription drugs and on its Bad Ad Program
Healthy Skepticism is an international nonprofit membership association that aims to improve health by reducing harm from misleading health information
The Drug Promotion Database was developed by the World Health Organization Department of Essential Drugs & Medicines Policy and Health Action International Europe to address unethical and inappropriate drug promotion
doi:10.1371/journal.pmed.1000352
PMCID: PMC2957394  PMID: 20976098
12.  Motivations for Undertaking DNA Sequencing-Based Non-Invasive Prenatal Testing for Fetal Aneuploidy: A Qualitative Study with Early Adopter Patients in Hong Kong 
PLoS ONE  2013;8(11):e81794.
Background
A newly introduced cell-free fetal DNA sequencing based non-invasive prenatal testing (DNA-NIPT) detects Down syndrome with sensitivity of 99% at early gestational stage without risk of miscarriage. Attention has been given to its public health implications; little is known from consumer perspectives. This qualitative study aimed to explore women’s motivations for using, and perceptions of, DNA-NIPT in Hong Kong.
Methods and Findings
In-depth interviews were conducted with 45 women who had undertaken DNA-NIPT recruited by purposive sampling based on socio-demographic and clinical characteristics. The sample included 31 women identified as high-risk from serum and ultrasound based Down syndrome screening (SU-DSS). Thematic narrative analysis examined informed-decision making of the test and identified the benefits and needs. Women outlined a number of reasons for accessing DNA-NIPT: reducing the uncertainty associated with risk probability-based results from SU-DSS, undertaking DNA-NIPT as a comprehensive measure to counteract risk from childbearing especially at advanced age, perceived predictive accuracy and absence of risk of harm to fetus. Accounts of women deemed high-risk or not high-risk are distinctive in a number of respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk. This group perceived SU-DSS as an unnecessary and confusing procedure because of its varying, protocol-dependent detection rates. Those women not deemed high-risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce anxiety even after receiving the negative result from SU-DSS.
Conclusions
DNA-NIPT was regarded positively by women who chose this method of screening over the routine, less expensive testing options. Given its perceived utility, health providers need to consider whether DNA-NIPT should be offered as part of universal routine care to women at high-risk for fetal aneuploidy. If this is the case, then further development of guidelines and quality assurance will be needed to provide a service suited to patients’ needs.
doi:10.1371/journal.pone.0081794
PMCID: PMC3842294  PMID: 24312358
13.  Interactions between Non-Physician Clinicians and Industry: A Systematic Review 
PLoS Medicine  2013;10(11):e1001561.
In a systematic review of studies of interactions between non-physician clinicians and industry, Quinn Grundy and colleagues found that many of the issues identified for physicians' industry interactions exist for non-physician clinicians.
Please see later in the article for the Editors' Summary
Background
With increasing restrictions placed on physician–industry interactions, industry marketing may target other health professionals. Recent health policy developments confer even greater importance on the decision making of non-physician clinicians. The purpose of this systematic review is to examine the types and implications of non-physician clinician–industry interactions in clinical practice.
Methods and Findings
We searched MEDLINE and Web of Science from January 1, 1946, through June 24, 2013, according to PRISMA guidelines. Non-physician clinicians eligible for inclusion were: Registered Nurses, nurse prescribers, Physician Assistants, pharmacists, dieticians, and physical or occupational therapists; trainee samples were excluded. Fifteen studies met inclusion criteria. Data were synthesized qualitatively into eight outcome domains: nature and frequency of industry interactions; attitudes toward industry; perceived ethical acceptability of interactions; perceived marketing influence; perceived reliability of industry information; preparation for industry interactions; reactions to industry relations policy; and management of industry interactions. Non-physician clinicians reported interacting with the pharmaceutical and infant formula industries. Clinicians across disciplines met with pharmaceutical representatives regularly and relied on them for practice information. Clinicians frequently received industry “information,” attended sponsored “education,” and acted as distributors for similar materials targeted at patients. Clinicians generally regarded this as an ethical use of industry resources, and felt they could detect “promotion” while benefiting from industry “information.” Free samples were among the most approved and common ways that clinicians interacted with industry. Included studies were observational and of varying methodological rigor; thus, these findings may not be generalizable. This review is, however, the first to our knowledge to provide a descriptive analysis of this literature.
Conclusions
Non-physician clinicians' generally positive attitudes toward industry interactions, despite their recognition of issues related to bias, suggest that industry interactions are normalized in clinical practice across non-physician disciplines. Industry relations policy should address all disciplines and be implemented consistently in order to mitigate conflicts of interest and address such interactions' potential to affect patient care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Making and selling health care goods (including drugs and devices) and services is big business. To maximize the profits they make for their shareholders, companies involved in health care build relationships with physicians by providing information on new drugs, organizing educational meetings, providing samples of their products, giving gifts, and holding sponsored events. These relationships help to keep physicians informed about new developments in health care but also create the potential for causing harm to patients and health care systems. These relationships may, for example, result in increased prescription rates of new, heavily marketed medications, which are often more expensive than their generic counterparts (similar unbranded drugs) and that are more likely to be recalled for safety reasons than long-established drugs. They may also affect the provision of health care services. Industry is providing an increasingly large proportion of routine health care services in many countries, so relationships built up with physicians have the potential to influence the commissioning of the services that are central to the treatment and well-being of patients.
Why Was This Study Done?
As a result of concerns about the tension between industry's need to make profits and the ethics underlying professional practice, restrictions are increasingly being placed on physician–industry interactions. In the US, for example, the Physician Payments Sunshine Act now requires US manufacturers of drugs, devices, and medical supplies that participate in federal health care programs to disclose all payments and gifts made to physicians and teaching hospitals. However, other health professionals, including those with authority to prescribe drugs such as pharmacists, Physician Assistants, and nurse practitioners are not covered by this legislation or by similar legislation in other settings, even though the restructuring of health care to prioritize primary care and multidisciplinary care models means that “non-physician clinicians” are becoming more numerous and more involved in decision-making and medication management. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers examine the nature and implications of the interactions between non-physician clinicians and industry.
What Did the Researchers Do and Find?
The researchers identified 15 published studies that examined interactions between non-physician clinicians (Registered Nurses, nurse prescribers, midwives, pharmacists, Physician Assistants, and dieticians) and industry (corporations that produce health care goods and services). They extracted the data from 16 publications (representing 15 different studies) and synthesized them qualitatively (combined the data and reached word-based, rather than numerical, conclusions) into eight outcome domains, including the nature and frequency of interactions, non-physician clinicians' attitudes toward industry, and the perceived ethical acceptability of interactions. In the research the authors identified, non-physician clinicians reported frequent interactions with the pharmaceutical and infant formula industries. Most non-physician clinicians met industry representatives regularly, received gifts and samples, and attended educational events or received educational materials (some of which they distributed to patients). In these studies, non-physician clinicians generally regarded these interactions positively and felt they were an ethical and appropriate use of industry resources. Only a minority of non-physician clinicians felt that marketing influenced their own practice, although a larger percentage felt that their colleagues would be influenced. A sizeable proportion of non-physician clinicians questioned the reliability of industry information, but most were confident that they could detect biased information and therefore rated this information as reliable, valuable, or useful.
What Do These Findings Mean?
These and other findings suggest that non-physician clinicians generally have positive attitudes toward industry interactions but recognize issues related to bias and conflict of interest. Because these findings are based on a small number of studies, most of which were undertaken in the US, they may not be generalizable to other countries. Moreover, they provide no quantitative assessment of the interaction between non-physician clinicians and industry and no information about whether industry interactions affect patient care outcomes. Nevertheless, these findings suggest that industry interactions are normalized (seen as standard) in clinical practice across non-physician disciplines. This normalization creates the potential for serious risks to patients and health care systems. The researchers suggest that it may be unrealistic to expect that non-physician clinicians can be taught individually how to interact with industry ethically or how to detect and avert bias, particularly given the ubiquitous nature of marketing and promotional materials. Instead, they suggest, the environment in which non-physician clinicians practice should be structured to mitigate the potentially harmful effects of interactions with industry.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001561.
This study is further discussed in a PLOS Medicine Perspective by James S. Yeh and Aaron S. Kesselheim
The American Medical Association provides guidance for physicians on interactions with pharmaceutical industry representatives, information about the Physician Payments Sunshine Act, and a toolkit for preparing Physician Payments Sunshine Act reports
The International Council of Nurses provides some guidance on industry interactions in its position statement on nurse-industry relations
The UK General Medical Council provides guidance on financial and commercial arrangements and conflicts of interest as part of its good medical practice website, which describes what is required of all registered doctors in the UK
Understanding and Responding to Pharmaceutical Promotion: A Practical Guide is a manual prepared by Health Action International and the World Health Organization that schools of medicine and pharmacy can use to train students how to recognize and respond to pharmaceutical promotion.
The Institute of Medicine's Report on Conflict of Interest in Medical Research, Education, and Practice recommends steps to identify, limit, and manage conflicts of interest
The University of California, San Francisco, Office of Continuing Medical Education offers a course called Marketing of Medicines
doi:10.1371/journal.pmed.1001561
PMCID: PMC3841103  PMID: 24302892
14.  Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats 
One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic groups compared with those in diabetic and Pae-treated diabetic groups. In addition, superoxide dismutase activity and thiobarbituric acid reactive substances content significantly changed in the presence of Pae + DSS. We therefore conclude that both Pae and DSS treatments prevent diabetes-induced vascular damage. Furthermore, Pae + DSS prove to be the most efficient treatment regimen. The combination of Pae and DSS produce significant protective effects through the reduction of oxidative stress and through intracellular Ca2+ regulatory mechanisms.
doi:10.3390/ijms131114565
PMCID: PMC3509597  PMID: 23203081
paeonol; danshensu; vasodilation; endothelium dysfunction; vascular smooth muscle cell; oxidative stress; Ca2+ channel
15.  Key Performance Indicators for the Assessment of Pediatric Pharmacotherapeutic Guidance 
Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25–50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide patient-specific pharmacotherapy guidance as part of our pediatric knowledgebase initiative. For the top 25 most utilized agents at our institution over the last 6 years, KPI score ranged from 35 (dexamethasone) to 77 (cefazolin and ampicillin) with an average score of 55. Prototype DSS for tacrolimus and methotrexate are strongly supported by the KPI scoring which ranks their selection in the top 5% of drugs on formulary. KPI metrics provide an objective means of ranking agents for which pediatric pharmacotherapeutic guidance is clearly needed.
doi:10.5863/1551-6776-13.3.141
PMCID: PMC3462038  PMID: 23055875
key performance indicators; medical need; pediatric pharmacotherapy; utilization
16.  Retrospective review of rectal cancer surgery in northern Alberta 
Canadian Journal of Surgery  2013;56(4):E51-E58.
Introduction
Previous studies, including research published more than 10 years ago in Northern Alberta, have demonstrated improved outcomes with increased surgical volume and subspecialisation in the treatment of rectal cancer. We sought to examine contemporary rectal cancer care in the same region to determine whether practice patterns have changed and whether outcomes have improved.
Methods
We reviewed the charts of all patients with rectal adenocarcinoma diagnosed between 1998 and 2003 who had a potentially curative resection. The main outcomes examined were 5-year local recurrence (LR) and disease-specific survival (DSS). Surgeons were classified into 3 groups according to training and volume, and we compared outcome measures among them. We also compared our results to those of the previous study from our region.
Results
We included 433 cases in the study. Subspecialty-trained colorectal surgeons performed 35% of all surgeries in our study compared to 16% in the previous study. The overall 5-year LR rate and DSS in our study were improved compared to the previous study. On multivariate analysis, the only factor associated with increased 5-year LR was presence of obstruction, and the factors associated with decreased 5-year DSS were high-volume noncolorectal surgeons, presence of obstruction and increased stage.
Conclusion
Over the past 10 years, the long-term outcomes of treatment for rectal cancer have improved. We found that surgical subspecialization was associated with improved DSS but not LR. Increased surgical volume was not associated with LR or DSS.
doi:10.1503/cjs.006612
PMCID: PMC3728253  PMID: 23883504
17.  MED1/337: Using the Internet to Deliver Decision Support Systems to Physicians 
Introduction
Scientifically based clinical guidelines are increasingly directing medical care. Two such guidelines are the National Asthma Education Program 2 (NAEP2) and the ATS/CDC Tuberculosis Guidelines. While these expert-derived guidelines are potentially very useful, it is difficult for individual physicians to be knowledgeable about all these guidelines and even more difficult for them to apply the guidelines to a specific patient care setting. Computer networks offer the potential to bridge this need and individualize guidelines to providers at the point of clinical contact.
Methods
Using content from the NAEP2 and the TB Guidelines, we developed two computer-based delivery systems using the Internet. Using CGI and NAEP2, we developed an algorithm to stage acute asthma disease severity and deliver specific recommendations to physicians. We tested the computer-delivered algorithm using patient scenarios. Using the TB Guidelines, we also developed an html-linked decision support tool to deliver appropriate treatment recommendations based on answering three clinical questions. We again tested the utility of the program using patient scenario testing.
Results
We first validated the asthma algorithm by comparing asthma expert's decisions with the decisions reached by non-pulmonary nurses using the computerized decision support system (DSS). Using the DSS, nurses scored the same as experts (89 ± 1.4% vs. 88 ± 3%; p=NS). Using the same test, we next compared internal medicine residents using the computerized DSS to residents using the paper version of NAEP2 asthma guidelines. Residents using the computerized DSS scored significantly better than residents using the paper-based NAEP2 guidelines (92 ± 1.7% vs. 84 ± 1.5%; p<.002). When we similarly compared residents using the computerized TB DSS to residents using a reference card, the residents using the computerized DSS scored significantly better (95.8% correct vs. 56.6%; p<.01).
Discussion
Clinical guidelines are increasingly common in chronic disease management. Previous work has demonstrated that traditional educational interventions are minimally effective at altering physician behavior. In other settings, learning occurs best when coupled to relevant activity. Computers can aid with this learning by providing relevant information to the clinician when they need it to make clinical decisions. Using two different sets of guidelines, we have demonstrated that computer-based DSS's delivered over the Internet are more effective than traditional resources in improving physician performance as measured by compliance with guidelines. We conclude that guidelines can be adapted to deliver individualized recommendations using the Internet and that computer-delivered recommendations are effective at improving physician compliance.
doi:10.2196/jmir.1.suppl1.e44
PMCID: PMC1761817
Asthma; Tuberculosis; Education; Guidelines; Computer; Decision support
18.  Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome 
Background
Dengue virus (DV) infection is one of the most important mosquito-borne diseases in the tropics. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. Protective and/or pathogenic T cell immunity is supposed to be important in the pathogenesis of DHF and DSS.
Methodology/Principal Findings
To identify HLA alleles controlling T cell immunity against dengue virus (DV), we performed a hospital-based case control study at Children's Hospital No.2, Ho Chi Minh City (HCMC), and Vinh Long Province Hospital (VL) in Southern Vietnam from 2002 to 2005. A total of 211 and 418 patients with DHF and DSS, respectively, diagnosed according to the World Health Organization (WHO) criteria, were analyzed for their characteristic HLA-A, -B and -DRB1 alleles. Four hundred fifty healthy children (250 from HCMC and 200 from VL) of the same Kinh ethnicity were also analyzed as population background. In HLA class I, frequency of the HLA-A*24 showed increased tendency in both DHF and DSS patients, which reproduced a previous study. The frequency of A*24 with histidine at codon 70 (A*2402/03/10), based on main anchor binding site specificity analysis in DSS and DHF patients, was significantly higher than that in the population background groups (HCMC 02-03 DSS: OR = 1.89, P = 0.008, DHF: OR = 1.75, P = 0.033; VL 02-03 DSS: OR = 1.70, P = 0.03, DHF: OR = 1.46, P = 0.38; VL 04-05 DSS: OR = 2.09, P = 0.0075, DHF: OR = 2.02, P = 0.038). In HLA class II, the HLA-DRB1*0901 frequency was significantly decreased in secondary infection of DSS in VL 04-05 (OR = 0.35, P = 0.0025, Pc = 0.03). Moreover, the frequency of HLA-DRB1*0901 in particular was significantly decreased in DSS when compared with DHF in DEN-2 infection (P = 0.02).
Conclusion
This study improves our understanding of the risk of HLA-class I for severe outcome of DV infection in the light of peptide anchor binding site and provides novel evidence that HLA-class II may control disease severity (DHF to DSS) in DV infection.
Author Summary
Dengue has become one of the most common viral diseases transmitted by infected mosquitoes (with any of the four dengue virus serotypes: DEN-1, -2, -3, or -4). It may present as asymptomatic or illness, ranging from mild to severe disease. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. The pathogenesis of DHF/DSS, however, is not yet completely understood. The immune response, virus virulence, and host genetic background are considered to be risk factors contributing to disease severity. Human leucocyte antigens (HLA) expressed on the cell surface function as antigen presenting molecules and those polymorphism can change individuals' immune response. We investigated the HLA-A, -B (class I), and -DRB1 (class II) polymorphism in Vietnamese children with different severity (DHF/DSS) by a hospital-based case-control study. The study showed persons carrying HLA-A*2402/03/10 are about 2 times more likely to have severe dengue infection than others. On the other hand, HLA-DRB1*0901 persons are less likely to develop DSS with DEN-2 virus infection. These results clearly demonstrated that HLA controlled the susceptibility to severe forms of DV infection.
doi:10.1371/journal.pntd.0000304
PMCID: PMC2553281  PMID: 18827882
19.  Child Welfare Workers’ Adoption of Decision Support Technology 
Child welfare workers must process complex information in deciding to refer clients to appropriate mental health services. Decision support systems (DSS) have been demonstrated in other fields to be an important tool, yet little research has been done in child welfare. This study focused on the adoption of a specific DSS into child welfare practice. Quantitative analysis was used to demonstrate the diffusion of innovation process among a sample of state child welfare workers, while qualitative analysis was used to explain the facilitators and barriers to DSS adoption. Results indicate that for DSSs to be widely adopted in child welfare practice, they should be integrated into the referral system and include workers’ knowledge and experiences with referral resources. For successful adoption, DSSs need to respect the natural logic and flow of worker interaction, as well as organizational constraints.
doi:10.1080/15228830902749039
PMCID: PMC2829997  PMID: 20198123
decision support technology; child welfare; diffusion of innovations
20.  Overcoming Limitations of Data Entry for the Semi-Automated Detection of Drug Orphans in the EMR 
Sophisticated decision support systems (DSS) can reduce preventable medical errors. A standalone DSS prototype was built to identify drug-disease mismatches in the electronic medical record (EMR). When drugs fail to match a known problem on the problem list (drug orphans), either the problem list is deficient or the drug was ordered in error. We tested the performance of an integrated DSS prototype by improving the data exchange with the standalone DSS prototype. By implementing a screen capture tool, we were able to accelerate data entry into the DSS prototype through the semi-automated operation. Preliminary results revealed a marked increase in the rate of data entry during testing the DSS prototype. The accelerated data entry streamlines workflow and promotes physician’s acceptance of the DSS.
PMCID: PMC1839553  PMID: 17238586
21.  Development and Testing of a Scale to Assess Physician Attitudes about Handheld Computers with Decision Support 
Objective
The authors developed and evaluated a rating scale, the Attitudes toward Handheld Decision Support Software Scale (H-DSS), to assess physician attitudes about handheld decision support systems.
Design
The authors conducted a prospective assessment of psychometric characteristics of the H-DSS including reliability, validity, and responsiveness. Participants were 82 Internal Medicine residents. A higher score on each of the 14 five-point Likert scale items reflected a more positive attitude about handheld DSS. The H-DSS score is the mean across the fourteen items. Attitudes toward the use of the handheld DSS were assessed prior to and six months after receiving the handheld device.
Statistics
Cronbach's Alpha was used to assess internal consistency reliability. Pearson correlations were used to estimate and detect significant associations between scale scores and other measures (validity). Paired sample t-tests were used to test for changes in the mean attitude scale score (responsiveness) and for differences between groups.
Results
Internal consistency reliability for the scale was α = 0.73. In testing validity, moderate correlations were noted between the attitude scale scores and self-reported Personal Digital Assistant (PDA) usage in the hospital (correlation coefficient = 0.55) and clinic (0.48), p < 0.05 for both. The scale was responsive, in that it detected the expected increase in scores between the two administrations (3.99 (s.d. = 0.35) vs. 4.08, (s.d. = 0.34), p < 0.005).
Conclusion
The authors' evaluation showed that the H-DSS scale was reliable, valid, and responsive. The scale can be used to guide future handheld DSS development and implementation.
doi:10.1197/jamia.M2096
PMCID: PMC1561800  PMID: 16799120
22.  Survival in 12,653 breast cancer patients with extensive axillary lymph node metastasis in the anthracycline era 
Institutional data are conflicting regarding the prognosis of breast cancer patients with extensive (≥10) axillary lymph node (ALN) metastases. We hypothesized that overall survival (OS) and disease specific survival (DSS) improved after the introduction of anthracycline-based therapy in 1997. We used the Surveillance, Epidemiology, and End results (SEER) database to identify breast cancer patients with ≥10 ALN metastases diagnosed between 1988 and 2004. Patients were categorized according to whether they were diagnosed prior to the FDA approval of anthracyclines (pre-anthracycline era, pre-AE) or after approval (post-anthracycline era, post-AE). Univariate analyses of OS and DSS were performed using the Kaplan–Meier method and differences assessed via the log rank test. Anthracycline era as an independent predictor of OS and DSS was evaluated using Cox proportional hazards models with patient age, hormone receptor status, tumor size, use of radiation therapy, and number of metastatic ALNs as covariates. Entry criteria were met by 12,653 patients. Of these, 5,655 (44.7%) and 6,998 (55.3%) were treated in the pre-AE and post-AE, respectively. On univariate analysis, post-AE patients experienced significantly improved rates of OS (P<0.001) and DSS (P<0.001) relative to pre-AE patients. On multivariate analysis, treatment in the post-AE favorably influenced both OS (Hazard Ratio [HR] 0.90, 95% Confidence Interval [CI] 0.84–0.96) and DSS (HR 0.84, CI 0.79–0.91). Both OS and DSS are poor in patients with extensive ALN metastases. Patients with advanced breast cancer treated in the post-AE demonstrated superior OS and DSS.
doi:10.1007/s12032-009-9396-4
PMCID: PMC2930938  PMID: 20049562
Anthracycline; Advanced breast cancer; Survival; SEER
23.  Prescription of oxygen concentrators and survival in Northern Ireland. 
The Ulster Medical Journal  1997;66(2):86-91.
Long-term oxygen therapy (LTOT) has been shown to prolong survival and to improve quality of life in patients with chronic obstructive pulmonary disease (COPD) and in respiratory failure. In Northern Ireland oxygen concentrators have been available on prescription since August 1986, initially on a restricted basis from hospital physicians only. This was followed by open prescribing from April 1989, when concentrators could be prescribed by general practitioners. This study examined prescribing habits of LTOT during both periods, and patient survival. Case notes of all prescriptions of oxygen concentrators in Northern Ireland (to April 1991) were reviewed. Prescription criteria and advice regarding usage during both periods were analysed. A questionnaire survey of subjects during open prescribing documented the advice given at the time of prescription and current usage. 164 charts of 178 total installations were available for review. During both periods many concentrators were installed without adherence to the prescribing criteria at the time (75% restricted, 48% open). The majority of these were on the advice of a consultant respiratory physician and only 14 were prescribed directly by GPs. 89 of 91 subjects receiving current LTOT during the study period completed questionnaires. Of the subjects prescribed LTOT during the restricted period, 2 subjects are still alive (median survival 19 m, range 0-104). From the open period, survival data was available on 107 of 129 subjects with 17 still alive (median survival 22 m, range 0-94). This study documents an inadequate rate of prescribing and a lack of conformity to guidelines in the provision of LTOT in Northern Ireland. We would suggest that familiarisation with the prescribing criteria, formal written advice at the time of prescription, appropriate follow up to ensure adequate supplementation and regular patient education on the use of LTOT would address these problems to a substantial degree.
PMCID: PMC2448871  PMID: 9414936
24.  Should colloid boluses be prioritized over crystalloid boluses for the management of dengue shock syndrome in the presence of ascites and pleural effusions? 
Background
Although the WHO guideline for the management of dengue fever considers the presence of ascites or pleural effusions in the diagnosis of DSS, it does not emphasize the importance of their presence when selecting fluids for resuscitation.
Case presentation
We highlight three patients with DSS who received boluses of crystalloids on priority basis as recommended by WHO guidelines during resuscitation. All three patients had varying degrees of third space fluid loss (ascites and pleural effusions) at the time of development of DSS. Ascites and pleural effusions were detected in all 3 patients at the time of shock irrespective of whether iv fluids were given or not. All three patients had documented liver involvement at the time of shock evidenced by elevation of AST (4800 iu/L, 5000 iu/L and 1960 iu/L). One patient who had profound shock died 6 hours after admission with evidence of acute pulmonary oedema in the convalescence phase. All of them needed CPAP ventilator support and potent diuretics.
Conclusions
We therefore feel that resuscitation of patients with DSS who already have third space fluid accumulation with crystalloid boluses on priority basis may contribute to recovery phase pulmonary oedema.
doi:10.1186/1471-2334-11-52
PMCID: PMC3056793  PMID: 21356095
25.  Comparison of direct machine parameter optimization versus fluence optimization with sequential sequencing in IMRT of hypopharyngeal carcinoma 
Background
To evaluate the effects of direct machine parameter optimization in the treatment planning of intensity-modulated radiation therapy (IMRT) for hypopharyngeal cancer as compared to subsequent leaf sequencing in Oncentra Masterplan v1.5.
Methods
For 10 hypopharyngeal cancer patients IMRT plans were generated in Oncentra Masterplan v1.5 (Nucletron BV, Veenendal, the Netherlands) for a Siemens Primus linear accelerator.
For optimization the dose volume objectives (DVO) for the planning target volume (PTV) were set to 53 Gy minimum dose and 59 Gy maximum dose, in order to reach a dose of 56 Gy to the average of the PTV. For the parotids a median dose of 22 Gy was allowed and for the spinal cord a maximum dose of 35 Gy. The maximum DVO to the external contour of the patient was set to 59 Gy. The treatment plans were optimized with the direct machine parameter optimization ("Direct Step & Shoot", DSS, Raysearch Laboratories, Sweden) newly implemented in Masterplan v1.5 and the fluence modulation technique ("Intensity Modulation", IM) which was available in previous versions of Masterplan already. The two techniques were compared with regard to compliance to the DVO, plan quality, and number of monitor units (MU) required per fraction dose.
Results
The plans optimized with the DSS technique met the DVO for the PTV significantly better than the plans optimized with IM (p = 0.007 for the min DVO and p < 0.0005 for the max DVO). No significant difference could be observed for compliance to the DVO for the organs at risk (OAR) (p > 0.05). Plan quality, target coverage and dose homogeneity inside the PTV were superior for the plans optimized with DSS for similar dose to the spinal cord and lower dose to the normal tissue. The mean dose to the parotids was lower for the plans optimized with IM. Treatment plan efficiency was higher for the DSS plans with (901 ± 160) MU compared to (1151 ± 157) MU for IM (p-value < 0.05).
Renormalization of the IM plans to the mean of the dose to 95% of the PTV (D95) of the DSS plans, resulted in similar target coverage and dose to the parotids for both strategies, at the cost of a significantly higher dose to the normal tissue and maximum dose to the target. The relative volume of the PTV receiving 107% or more of the prescription dose V107 increased to 35.5% ± 20.0% for the IM plan as compared to a mean of 0.9% ± 0.9% for the DSS plan.
Conclusion
The direct machine parameter optimization is a major improvement compared to the fluence modulation with subsequent leaf sequencing in Oncentra Masterplan v1.5. The resulting dose distribution complies better with the DVO and better plan quality is achieved for identical specification of DVO. An additional asset is the reduced number of MU as compared to IM.
doi:10.1186/1748-717X-2-33
PMCID: PMC2075520  PMID: 17822529

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