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1.  Creating an Online Dictionary of Abbreviations from MEDLINE 
Objective. The growth of the biomedical literature presents special challenges for both human readers and automatic algorithms. One such challenge derives from the common and uncontrolled use of abbreviations in the literature. Each additional abbreviation increases the effective size of the vocabulary for a field. Therefore, to create an automatically generated and maintained lexicon of abbreviations, we have developed an algorithm to match abbreviations in text with their expansions.
Design. Our method uses a statistical learning algorithm, logistic regression, to score abbreviation expansions based on their resemblance to a training set of human-annotated abbreviations. We applied it to Medstract, a corpus of MEDLINE abstracts in which abbreviations and their expansions have been manually annotated. We then ran the algorithm on all abstracts in MEDLINE, creating a dictionary of biomedical abbreviations. To test the coverage of the database, we used an independently created list of abbreviations from the China Medical Tribune.
Measurements. We measured the recall and precision of the algorithm in identifying abbreviations from the Medstract corpus. We also measured the recall when searching for abbreviations from the China Medical Tribune against the database.
Results. On the Medstract corpus, our algorithm achieves up to 83% recall at 80% precision. Applying the algorithm to all of MEDLINE yielded a database of 781,632 high-scoring abbreviations. Of all the abbreviations in the list from the China Medical Tribune, 88% were in the database.
Conclusion. We have developed an algorithm to identify abbreviations from text. We are making this available as a public abbreviation server at \url{http://abbreviation.stanford.edu/}.
doi:10.1197/jamia.M1139
PMCID: PMC349378  PMID: 12386112
2.  Mapping Abbreviations to Full Forms in Biomedical Articles 
Objective: To develop methods that automatically map abbreviations to their full forms in biomedical articles.
Methods: The authors developed two methods of mapping defined and undefined abbreviations (defined abbreviations are paired with their full forms in the articles, whereas undefined ones are not). For defined abbreviations, they developed a set of pattern-matching rules to map an abbreviation to its full form and implemented the rules into a software program, AbbRE (for “abbreviation recognition and extraction”). Using the opinions of domain experts as a reference standard, they evaluated the recall and precision of AbbRE for defined abbreviations in ten biomedical articles randomly selected from the ten most frequently cited medical and biological journals. They also measured the percentage of undefined abbreviations in the same set of articles, and they investigated whether they could map undefined abbreviations to any of four public abbreviation databases (GenBank LocusLink, swissprot, LRABR of the UMLS Specialist Lexicon, and Bioabacus).
Results: AbbRE had an average 0.70 recall and 0.95 precision for the defined abbreviations. The authors found that an average of 25 percent of abbreviations were defined in biomedical articles and that of a randomly selected subset of undefined abbreviations, 68 percent could be mapped to any of four abbreviation databases. They also found that many abbreviations are ambiguous (i.e., they map to more than one full form in abbreviation databases).
Conclusion: AbbRE is efficient for mapping defined abbreviations. To couple AbbRE with abbreviation databases for the mapping of undefined abbreviations, not only exhaustive abbreviation databases but also a method to resolve the ambiguity of abbreviations in the databases are needed.
doi:10.1197/jamia.M0913
PMCID: PMC344586  PMID: 11971887
3.  A Study of Abbreviations in Clinical Notes 
Various natural language processing (NLP) systems have been developed to unlock patient information from narrative clinical notes in order to support knowledge based applications such as error detection, surveillance and decision support. In many clinical notes, abbreviations are widely used without mention of their definitions, which is very different from the use of abbreviations in the biomedical literature. Thus, it is critical, but more challenging, for NLP systems to correctly interpret abbreviations in these notes. In this paper we describe a study of a two-step model for building a clinical abbreviation database: first, abbreviations in a text corpus were detected and then a sense inventory was built for those that were found. Four detection methods were developed and evaluated. Results showed that the best detection method had a precision of 91.4% and recall of 80.3%. A simple method was used to build sense inventories from two different knowledge sources: the Unified Medical Language System (UMLS) and a MEDLINE abbreviation database (ADAM). Evaluation showed the inventory from the UMLS appeared to be the more appropriate of the two for defining the sense of abbreviations, but was not ideal. It covered 35% of the senses and had an ambiguity rate of 40% for those that were covered. However, annotation by domain experts appears necessary for uncovered abbreviations and to determine the correct senses.
PMCID: PMC2655910  PMID: 18693951
4.  Avoiding Potential Medication Errors Associated with Non-intuitive Medication Abbreviations 
Background:
Pharmaceutical companies use a variety of abbreviations to denote short- and long-acting medications. Errors involving the administration of these medications are frequently reported.
Objectives:
To evaluate comprehension rates for abbreviations used to denote short- and long-acting medications and to evaluate whether changes to medication labels could reduce potential errors in the selection and administration of medications.
Methods:
In phase 1 of the study, nursing staff were asked to define 4 abbreviations and then to categorize them by release rate. In phase 2, a simulation exercise, nursing staff were asked if it would be appropriate to administer a medication illustrated in a photograph (oxycodone CR 5-mg blister pack) on the basis of information highlighted in a screen shot of an electronic medication administration record (order for oxycodone 5 mg). Three different presentations were used to identify the medication in the medication administration record and on the drug label.
Results:
In phase 1, 10 (28%) of 36 nursing staff members knew what all 4 abbreviations meant, and 14 (39%) correctly classified all 4 abbreviations as indicating a short- or a long-acting medication. In the simulation exercise (phase 2), labelling changes reduced the likelihood of a potential medication administration error.
Conclusions:
Most abbreviations used to indicate short- versus long-acting medications were not correctly understood by study participants. Of more concern was the incorrect interpretation of some abbreviations as indicating the opposite release rate (e.g., “ER” interpreted as meaning “emergency release”, rather than “extended release”, with incorrect classification as a short-acting medication). This evaluation highlighted the potential consequences of using non-intuitive abbreviations to differentiate high-risk medications having different release rates.
PMCID: PMC3161798  PMID: 22479066
medication abbreviations; release rate; medication error; human factors; abréviations des médicaments; vitesse de libération; erreurs de médication; facteurs humains
5.  A study of abbreviations in the UMLS. 
Abbreviations are widely used in medicine. The understanding of abbreviations is important for medical language processing and information retrieval systems. The Unified Medical Language System (UMLS) contains a large number of abbreviations. We hypothesized that extracting and studying the UMLS abbreviations can be helpful for understanding the characteristics of abbreviations in medicine. In this paper, we describe a method for extracting abbreviations from the UMLS. We evaluated the method and studied the ambiguous nature of the abbreviations. In addition, the coverage of the UMLS abbreviations in medical reports was studied. Using our method, we extracted 163,666 unique (abbreviation, full form) pairs from the UMLS with a precision of 97.5%, and a recall of 96%. The UMLS abbreviations were highly ambiguous: 33.1% of abbreviations with six characters or less had multiple meanings; the average number of different full forms for all abbreviations with six characters or less was 2.28. The coverage of the UMLS abbreviations in medical reports was over 66%.
PMCID: PMC2243414  PMID: 11825217
6.  The impact of preprinted prescription forms on medication prescribing errors in an ophthalmology clinic in northeast Thailand: a non-randomised interventional study 
BMJ Open  2012;2(1):e000539.
Objectives
To understand the incidence and types of medication prescribing errors in a low resource setting ophthalmology clinic and to determine the impact of a preprinted prescription based on the hospital formulary (FormularyScript) on medication prescribing errors.
Design
Non-randomised interventional study.
Setting
Ophthalmology clinic in a teaching hospital in northeast Thailand.
Participants
4349 handwritten prescriptions collected from October 2009 to December 2009, and 4146 FormularyScripts collected from February 2010 to May 2010.
Primary and secondary outcome measures
All prescriptions from the handwritten and FormularyScript groups were analysed for medication error rates by types (legibility, ambiguous, incomplete, abbreviation and accuracy) and subtypes (drug name, strength, which eye, route and dispensed amount).
Results
Comparison of error rates in the two groups showed a 10-fold reduction in the overall error rate using FormularyScript (32.9%–3.5%, p<0.001). FormularyScripts were associated with statistically significant (p<0.001) decreases in the following error types: legibility (16.1%–0.1%), incomplete (16.1%–0.1%) and abbreviation (3.1%–0.3%). There was no statistically significant change in accuracy errors (0.8%–0.6%, p=0.21). Ambiguous errors increased with FormularyScripts (0.6%–2.5%, p<0.001), likely due to the introduction of new ways to make errors. Decreases were seen in all legibility, abbreviation and accuracy error subtypes, and four out of six incomplete error subtypes. There were statistically significant increases in both ambiguous error subtypes: which eye (0.3%–2.5%, p<0.001) and drug name (0.3%–0.6%, p=0.03).
Conclusions
In our study population, outpatient medication prescribing errors were common and primarily due to legibility and incomplete error types. A preprinted prescription form has the potential to decrease medication prescribing errors related to legibility, incomplete prescribing information and use of unacceptable abbreviations without changing the overall rate of accuracy errors. However, new error types can occur.
Article summary
Article focus
Little is known about the frequency and types of medication prescribing errors in developing countries, especially outpatient settings.
Computerised prescribing systems are usually not feasible in low resource settings; however, a preprinted form may be an alternative.
Key messages
Medication prescribing errors are common in outpatient ophthalmology clinics and are primarily due to legibility and incomplete information.
Preprinted prescription forms have the potential to decrease medication prescribing errors related to legibility, incomplete prescribing information and use of unacceptable abbreviations without changing the overall rate of accuracy errors, but new error types can be introduced.
Any new medication prescribing system needs to be carefully monitored for unintended consequences. Working closely with physicians and pharmacists to optimise design and providing adequate training for users are important considerations in minimising the introduction of new ways of making errors.
Strengths and limitations of this study
The main strengths of this study are that it demonstrates that a low cost alternative to computerised prescribing exists and is effective at reducing the most common types of medication prescribing errors.
Important limitations of this study are that it is a non-randomised study conducted at a single site, the subjective nature of determining and classifying error types such as legibility, the FormularyScript did not include all necessary medications and physicians were aware that the prescriptions were being analysed for prescribing errors.
doi:10.1136/bmjopen-2011-000539
PMCID: PMC3289984  PMID: 22365953
7.  A novel abbreviation standard for organobromine, organochlorine and organophosphorus flame retardants and some characteristics of the chemicals 
Environment international  2012;49C:57-82.
Ever since the interest in organic environmental contaminants first emerged 50 years ago, there has been a need to present discussion of such chemicals and their transformation products using simple abbreviations so as to avoid the repetitive use of long chemical names. As the number of chemicals of concern has increased, the number of abbreviations has also increased dramatically, sometimes resulting in the use of different abbreviations for the same chemical. In this article, we propose abbreviations for flame retardants (FRs) substituted with bromine or chlorine atoms or including a functional group containing phosphorus, i.e. BFRs, CFRs and PFRs, respectively. Due to the large number of halogenated and organophosphorus FRs, it has become increasingly important to develop a strategy for abbreviating the chemical names of FRs. In this paper, a two step procedure is proposed for deriving practical abbreviations (PRABs) for the chemicals discussed. In the first step, structural abbreviations (STABs) are developed using specific STAB criteria based on the FR structure. However, since several of the derived STABs are complicated and long, we propose instead the use of PRABs. These are, commonly, an extract of the most essential part of the STAB, while also considering abbreviations previously used in the literature. We indicate how these can be used to develop an abbreviation that can be generally accepted by scientists and other professionals involved in FR related work. Tables with PRABs and STABs for BFRs, CFRs and PFRs are presented, including CAS (Chemical Abstract Service) numbers, notes of abbreviations that have been used previously, CA (Chemical Abstract) name, common names and trade names, as well as some fundamental physico-chemical constants.
doi:10.1016/j.envint.2012.08.003
PMCID: PMC3483428  PMID: 22982223
Brominated flame retardants; Chlorinated flame retardants; Phosphorus flame retardants; Nomenclature; Abbreviations; Physico-chemical properties
8.  Intervention to reduce the use of unsafe abbreviations in a teaching hospital 
Objectives
To determine the effectiveness of a two-phase intervention designed to reduce the use of unsafe abbreviations.
Methods
An observational prospective study was conducted at the King Khalid University Hospital in Riyadh, Saudi Arabia during May–September 2009. A list of unsafe abbreviations was formulated based on the recommendations of the Institute for Safe Medication Practices. The first 7000 medication orders written at the beginning of each period were collected. Phase one of the intervention involved educating health care professionals about the dangers of using unsafe abbreviations. In the second phase of the intervention, a policy was approved that prohibited the use of unsafe abbreviations hospital-wide. Then, another educational campaign targeted toward prescribers was organized. Descriptive statistics are used in this paper to present the results.
Results
At baseline, we identified 1980 medication abbreviations used in 7000 medication orders (28.3%). Three months after phase one of the intervention, the number of abbreviations found in 7000 medication orders had decreased to 1489 (21.3%). Six months later, after phase two of the intervention, the number of abbreviations used had decreased to 710 (10%). During this phase, the use of all abbreviations had declined relative to the baseline and phase one use levels. The decrease in the use of abbreviations was statistically significant in all three periods (P < 0.001).
Conclusion
The implementation of a complex intervention program reduced the use of unsafe abbreviations by 65%.
doi:10.1016/j.jsps.2012.10.006
PMCID: PMC3745070  PMID: 23960844
Unsafe abbreviations; Medications
9.  Allie: a database and a search service of abbreviations and long forms 
Many abbreviations are used in the literature especially in the life sciences, and polysemous abbreviations appear frequently, making it difficult to read and understand scientific papers that are outside of a reader’s expertise. Thus, we have developed Allie, a database and a search service of abbreviations and their long forms (a.k.a. full forms or definitions). Allie searches for abbreviations and their corresponding long forms in a database that we have generated based on all titles and abstracts in MEDLINE. When a user query matches an abbreviation, Allie returns all potential long forms of the query along with their bibliographic data (i.e. title and publication year). In addition, for each candidate, co-occurring abbreviations and a research field in which it frequently appears in the MEDLINE data are displayed. This function helps users learn about the context in which an abbreviation appears. To deal with synonymous long forms, we use a dictionary called GENA that contains domain-specific terms such as gene, protein or disease names along with their synonymic information. Conceptually identical domain-specific terms are regarded as one term, and then conceptually identical abbreviation-long form pairs are grouped taking into account their appearance in MEDLINE. To keep up with new abbreviations that are continuously introduced, Allie has an automatic update system. In addition, the database of abbreviations and their long forms with their corresponding PubMed IDs is constructed and updated weekly.
Database URL: The Allie service is available at http://allie.dbcls.jp/.
doi:10.1093/database/bar013
PMCID: PMC3077826  PMID: 21498548
10.  A study of abbreviations in MEDLINE abstracts. 
Abbreviations are widely used in writing, and the understanding of abbreviations is important for natural language processing applications. Abbreviations are not always defined in a document and they are highly ambiguous. A knowledge base that consists of abbreviations with their associated senses and a method to resolve the ambiguities are needed. In this paper, we studied the UMLS coverage, textual variants of senses, and the ambiguity of abbreviations in MEDLINE abstracts. We restricted our study to three-letter abbreviations which were defined using parenthetical expressions. When grouping similar expansions together and representing senses using groups, we found that after ignoring senses where the total number of occurrences within the corresponding group was less than 100, 82.8% of the senses matched the UMLS, covered over 93% of occurrences that were considered, and had an average of 7.74 expansions for each sense. Abbreviations are highly ambiguous: 81.2% of the abbreviations were ambiguous, and had an average of 16.6 senses. However, after ignoring senses with occurrences of less than 5, 64.6% of the abbreviations were ambiguous, and had an average of 4.91 senses.
PMCID: PMC2244212  PMID: 12463867
11.  Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of multidisciplinary care (MDC) compared with usual care (UC, single health care provider) for the treatment of stable chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Chronic obstructive pulmonary disease is a progressive disorder with episodes of acute exacerbations associated with significant morbidity and mortality. Cigarette smoking is linked causally to COPD in more than 80% of cases. Chronic obstructive pulmonary disease is among the most common chronic diseases worldwide and has an enormous impact on individuals, families, and societies through reduced quality of life and increased health resource utilization and mortality.
The estimated prevalence of COPD in Ontario in 2007 was 708,743 persons.
Technology
Multidisciplinary care involves professionals from a range of disciplines, working together to deliver comprehensive care that addresses as many of the patient’s health care and psychosocial needs as possible.
Two variables are inherent in the concept of a multidisciplinary team: i) the multidisciplinary components such as an enriched knowledge base and a range of clinical skills and experiences, and ii) the team components, which include but are not limited to, communication and support measures. However, the most effective number of team members and which disciplines should comprise the team for optimal effect is not yet known.
Research Question
What is the effectiveness and cost-effectiveness of MDC compared with UC (single health care provider) for the treatment of stable COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on July 19, 2010 using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 1995 until July 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search.
Inclusion Criteria
health technology assessments, systematic reviews, or randomized controlled trials
studies published between January 1995 and July 2010;
COPD study population
studies comparing MDC (2 or more health care disciplines participating in care) compared with UC (single health care provider)
Exclusion Criteria
grey literature
duplicate publications
non-English language publications
study population less than 18 years of age
Outcomes of Interest
hospital admissions
emergency department (ED) visits
mortality
health-related quality of life
lung function
Quality of Evidence
The quality of each included study was assessed, taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Six randomized controlled trials were obtained from the literature search. Four of the 6 studies were completed in the United States. The sample size of the 6 studies ranged from 40 to 743 participants, with a mean study sample between 66 and 71 years of age. Only 2 studies characterized the study sample in terms of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD stage criteria, and in general the description of the study population in the other 4 studies was limited. The mean percent predicted forced expiratory volume in 1 second (% predicted FEV1) among study populations was between 32% and 59%. Using this criterion, 3 studies included persons with severe COPD and 2 with moderate COPD. Information was not available to classify the population in the sixth study.
Four studies had MDC treatment groups which included a physician. All studies except 1 reported a respiratory specialist (i.e., respiratory therapist, specialist nurse, or physician) as part of the multidisciplinary team. The UC group was comprised of a single health care practitioner who may or may not have been a respiratory specialist.
A meta-analysis was completed for 5 of the 7 outcome measures of interest including:
health-related quality of life,
lung function,
all-cause hospitalization,
COPD-specific hospitalization, and
mortality.
There was only 1 study contributing to the outcome of all-cause and COPD-specific ED visits which precluded pooling data for these outcomes. Subgroup analyses were not completed either because heterogeneity was not significant or there were a small number of studies that were meta-analysed for the outcome.
Quality of Life
Three studies reported results of quality of life assessment based on the St. George’s Respiratory Questionnaire (SGRQ). A mean decrease in the SGRQ indicates an improvement in quality of life while a mean increase indicates deterioration in quality of life. In all studies the mean change score from baseline to the end time point in the MDC treatment group showed either an improvement compared with the control group or less deterioration compared with the control group. The mean difference in change scores between MDC and UC groups was statistically significant in all 3 studies. The pooled weighted mean difference in total SGRQ score was −4.05 (95% confidence interval [CI], −6.47 to 1.63; P = 0.001). The GRADE quality of evidence was assessed as low for this outcome.
Lung Function
Two studies reported results of the FEV1 % predicted as a measure of lung function. A negative change from baseline infers deterioration in lung function and a positive change from baseline infers an improvement in lung function. The MDC group showed a statistically significant improvement in lung function up to 12 months compared with the UC group (P = 0.01). However this effect is not maintained at 2-year follow-up (P = 0.24). The pooled weighted mean difference in FEV1 percent predicted was 2.78 (95% CI, −1.82 to −7.37). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.
Hospital Admissions
All-Cause
Four studies reported results of all-cause hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 4 studies were pooled to determine a summary estimate. There is a statistically significant 25% relative risk (RR) reduction in all-cause hospitalizations in the MDC group compared with the UC group (P < 0.001). The index of heterogeneity (I2) value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.
COPD-Specific Hospitalization
Three studies reported results of COPD-specific hospital admissions in terms of number of persons with at least 1 admission during the follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically significant 33% RR reduction in all-cause hospitalizations in the MDC group compared with the UC group (P = 0.002). The I2 value is 0%, indicating no statistical heterogeneity between studies. The GRADE quality of evidence was assessed as moderate for this outcome, indicating that further research may change the estimate of effect.
Emergency Department Visits
All-Cause
Two studies reported results of all-cause ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically nonsignificant reduction in all-cause ED visits when data from these 2 studies are pooled (RR, 0.64; 95% CI, 0.31 to −1.33; P = 0.24). The GRADE quality of evidence was assessed as very low for this outcome indicating that an estimate of effect is uncertain.
COPD-Specific
One study reported results of COPD-specific ED visits in terms of number of persons with at least 1 visit during the follow-up period. There is a statistically significant 41% reduction in COPD-specific ED visits when the data from these 2 studies are pooled (RR, 0.59; 95% CI, 0.43−0.81; P < 0.001). The GRADE quality of evidence was assessed as moderate for this outcome.
Mortality
Three studies reported the mortality during the study follow-up period. Estimates from these 3 studies were pooled to determine a summary estimate. There is a statistically nonsignificant reduction in mortality between treatment groups (RR, 0.81; 95% CI, 0.52−1.27; P = 0.36). The I2 value is 19%, indicating low statistical heterogeneity between studies. All studies had a 12-month follow-up period. The GRADE quality of evidence was assessed as low for this outcome.
Conclusions
Significant effect estimates with moderate quality of evidence were found for all-cause hospitalization, COPD-specific hospitalization, and COPD-specific ED visits (Table ES1). A significant estimate with low quality evidence was found for the outcome of quality of life (Table ES2). All other outcome measures were nonsignificant and supported by low or very low quality of evidence.
Summary of Dichotomous Data
Abbreviations: CI, confidence intervals; COPD, chronic obstructive pulmonary disease; n, number.
Summary of Continuous Data
Abbreviations: CI, confidence intervals; FEV1, forced expiratory volume in 1 second; n, number; SGRQ, St. George’s Respiratory Questionnaire.
PMCID: PMC3384374  PMID: 23074433
12.  Estimates of Outcomes Up to Ten Years after Stroke: Analysis from the Prospective South London Stroke Register 
PLoS Medicine  2011;8(5):e1001033.
Charles Wolfe and colleagues collected data from the South London Stroke Register on 3,373 first strokes registered between 1995 and 2006 and showed that between 20% and 30% of survivors have poor outcomes up to 10 years after stroke.
Background
Although stroke is acknowledged as a long-term condition, population estimates of outcomes longer term are lacking. Such estimates would be useful for planning health services and developing research that might ultimately improve outcomes. This burden of disease study provides population-based estimates of outcomes with a focus on disability, cognition, and psychological outcomes up to 10 y after initial stroke event in a multi-ethnic European population.
Methods and Findings
Data were collected from the population-based South London Stroke Register, a prospective population-based register documenting all first in a lifetime strokes since 1 January 1995 in a multi-ethnic inner city population. The outcomes assessed are reported as estimates of need and included disability (Barthel Index <15), inactivity (Frenchay Activities Index <15), cognitive impairment (Abbreviated Mental Test < 8 or Mini-Mental State Exam <24), anxiety and depression (Hospital Anxiety and Depression Scale >10), and mental and physical domain scores of the Medical Outcomes Study 12-item short form (SF-12) health survey. Estimates were stratified by age, gender, and ethnicity, and age-adjusted using the standard European population. Plots of outcome estimates over time were constructed to examine temporal trends and sociodemographic differences. Between 1995 and 2006, 3,373 first-ever strokes were registered: 20%–30% of survivors had a poor outcome over 10 y of follow-up. The highest rate of disability was observed 7 d after stroke and remained at around 110 per 1,000 stroke survivors from 3 mo to 10 y. Rates of inactivity and cognitive impairment both declined up to 1 y (280/1,000 and 180/1,000 survivors, respectively); thereafter rates of inactivity remained stable till year eight, then increased, whereas rates of cognitive impairment fluctuated till year eight, then increased. Anxiety and depression showed some fluctuation over time, with a rate of 350 and 310 per 1,000 stroke survivors, respectively. SF-12 scores showed little variation from 3 mo to 10 y after stroke. Inactivity was higher in males at all time points, and in white compared to black stroke survivors, although black survivors reported better outcomes in the SF-12 physical domain. No other major differences were observed by gender or ethnicity. Increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
Conclusions
Between 20% and 30% of stroke survivors have a poor range of outcomes up to 10 y after stroke. Such epidemiological data demonstrate the sociodemographic groups that are most affected longer term and should be used to develop longer term management strategies that reduce the significant poor outcomes of this group, for whom effective interventions are currently elusive.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, 15 million people have a stroke. About 5 million of these people die within a few days, and another 5 million are left disabled. Stroke occurs when the brain's blood supply is suddenly interrupted by a blood clot blocking a blood vessel in the brain (ischemic stroke, the commonest type of stroke) or by a blood vessel in the brain bursting (hemorrhagic stroke). Deprived of the oxygen normally carried to them by the blood, the brain cells near the blockage die. The symptoms of stroke depend on which part of the brain is damaged but include sudden weakness or paralysis along one side of the body, vision loss in one or both eyes, and confusion or trouble speaking or understanding speech. Anyone experiencing these symptoms should seek immediate medical attention because prompt treatment can limit the damage to the brain. Risk factors for stroke include age (three-quarters of strokes occur in people over 65 years old), high blood pressure, and heart disease.
Why Was This Study Done?
Post-stroke rehabilitation can help individuals overcome the physical disabilities caused by stroke, and drugs and behavioral counseling can reduce the risk of a second stroke. However, people can also have problems with cognition (thinking, awareness, attention, learning, judgment, and memory) after a stroke, and they can become depressed or anxious. These “outcomes” can persist for many years, but although stroke is acknowledged as a long-term condition, most existing data on stroke outcomes are limited to a year after the stroke and often focus on disability alone. Longer term, more extensive information is needed to help plan services and to help develop research to improve outcomes. In this burden of disease analysis, the researchers use follow-up data collected by the prospective South London Stroke Register (SLSR) to provide long-term population-based estimates of disability, cognition, and psychological outcomes after a first stroke. The SLSR has recorded and followed all patients of all ages in an inner area of South London after their first-ever stroke since 1995.
What Did the Researchers Do and Find?
Between 1995 and 2006, the SLSR recorded 3,373 first-ever strokes. Patients were examined within 48 hours of referral to SLSR, their stroke diagnosis was verified, and their sociodemographic characteristics (including age, gender, and ethnic origin) were recorded. Study nurses and fieldworkers then assessed the patients at three months and annually after the stroke for disability (using the Barthel Index, which measures the ability to, for example, eat unaided), inactivity (using the Frenchay Activities Index, which measures participation in social activities), and cognitive impairment (using the Abbreviated Mental Test or the Mini-Mental State Exam). Anxiety and depression and the patients' perceptions of their mental and physical capabilities were also assessed. Using preset cut-offs for each outcome, 20%–30% of stroke survivors had a poor outcome over ten years of follow-up. So, for example, 110 individuals per 1,000 population were judged disabled from three months to ten years, rates of inactivity remained constant from year one to year eight, at 280 affected individuals per 1,000 survivors, and rates of anxiety and depression fluctuated over time but affected about a third of the population. Notably, levels of inactivity were higher among men than women at all time points and were higher in white than in black stroke survivors. Finally, increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
What Do These Findings Mean?
Although the accuracy of these findings may be affected by the loss of some patients to follow-up, these population-based estimates of outcome measures for survivors of a first-ever stroke for up to ten years after the event provide concrete evidence that stroke is a lifelong condition with ongoing poor outcomes. They also identify the sociodemographic groups of patients that are most affected in the longer term. Importantly, most of the measured outcomes remain relatively constant (and worse than outcomes in an age-matched non-stroke-affected population) after 3–12 months, a result that needs to be considered when planning services for stroke survivors. In other words, these findings highlight the need for health and social services to provide long-term, ongoing assessment and rehabilitation for patients for many years after a stroke.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001033.
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); the US National Institute of Health SeniorHealth Web site has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
The UK National Health Service Choices Web site also provides information about stroke for patients and their families
MedlinePlus has links to additional resources about stroke (in English and Spanish)
More information about the South London Stroke Register is available
doi:10.1371/journal.pmed.1001033
PMCID: PMC3096613  PMID: 21610863
13.  Recurrent Dislocation of the Shoulder Joint 
Dr. Anthony F. DePalma is shown. Photograph provided with kind permission of the Art Committee of Thomas Jefferson University, Philadelphia, PA.
Dr. DePalma was the first editor of Clinical Orthopaedics and Related Research, established by the recently formed Association of Bone and Joint Surgeons. The idea of forming the Association of Bone and Joint surgeons had been conceived by Dr. Earl McBride of Oklahoma City in 1947, and organized by a group of twelve individuals (Drs. Earl McBride, Garrett Pipkin, Duncan McKeever, Judson Wilson, Fritz Teal, Louis Breck, Henry Louis Green, Howard Shorbe, Theodore Vinke, Paul Williams, Eugene Secord, and Frank Hand) [9]. The first organizational meeting was held in conjunction with the 1949 Annual Meeting of the AAOS [9] and the first annual meeting held April 1–2, 1949 in Oklahoma City. Drs. McBride and McKeever invited Dr. DePalma to attend that meeting and join the society. According to DePalma, “Even at this small gathering, there were whisperings of the need of another journal to provide an outlet for the many worthy papers written on clinical and basic science subjects” [7]. The decision to form a new journal was finalized in 1951, and Drs. DePalma and McBride signed a contract with J.B. Lippincott Company. Dr. DePalma was designated Editor-in-Chief, and the journal became a reality in 1953 with the publication of the first volume. From the outset he established the “symposium” as a unique feature, in which part of the articles were devoted to a particular topic. Dr. DePalma served as Editor for 13 years until 1966, when he resigned the position and recommended the appointment of Dr. Marshall R. Urist. At his retirement, Clinical Orthopaedics and Related Research was well established as a major journal.
Dr. Anthony F. DePalma was born in Philadelphia in 1904, the son of immigrants from Alberona in central Foggia, Italy [1]. He attended the University of Maryland for his premedical education, then Jefferson Medical College, from which he graduated in 1929. He then served a two-year internship (common at the time) at Philadelphia General Hospital. Jobs were scarce owing to the Depression, and he felt fortunate to obtain in 1931 a position as assistant surgeon at the Coaldale State Hospital, in Coaldale, Pennsylvania, a mining town. However, he became attracted to orthopaedics and looked for a preceptorship (postgraduate training in specialties was not well developed at this time before the establishments of Boards). In the fall of 1932, he was appointed as a preceptor at the New Jersey Orthopaedic Hospital, an extension of the New York Orthopaedic Hospital. In 1939 he acquired Board certification (the first board examination was offered in 1935 for a fee of $25.00 [2]) and was appointed to the NJOH staff [1].
Dr. DePalma volunteered for military service in 1942, and served first at the Parris Island Naval Hospital in South Carolina, then on the Rixey, a hospital ship. In addition to serving to evacuate casualties to New Zealand, his ship was involved in several of the Pacific island assaults (Guam, Leyte, Okinawa). In 1945, he was assigned to the Naval Hospital in Philadelphia [1].
On his return to Philadelphia, he contacted staff members at Jefferson Medical College, including the Chair, Dr. James Martin, and became good friends with Dr. Bruce Gill (a professor of Orthopaedics at the University of Pennsylvania, and one of the earliest Presidents of the AAOS). After he was discharged from the service, he joined the staff of the Department of Orthopaedic Surgery at Jefferson, where he remained the rest of his career. He succeeded Dr. Martin as Chair in 1950, a position he held until 1970 when he reached the mandatory retirement age of 65. He closed his practice and moved briefly to Pompano Beach, Florida, but the lure of academia proved too powerful, and in January, 1971, he accepted the offer to develop a Division of Orthopaedics at the New Jersey College of Medicine and became their Chair. He committed to a five-year period, and then again moved to Pompano Beach, only to take the Florida State Boards and open a private practice in 1977. His practice grew, and he continued that practice until 1983 at the age of nearly 79. Even then he continued to travel and lecture [1].
We reproduce here four of his many contributions on the shoulder. The first comes from his classic monograph, “Surgery of the Shoulder,” published by J. B. Lippincott in 1950 [2]. In this article he describes the evolutionary development of the shoulder, focusing on the distinction between various primates, and relates the anatomic changes to upright posture and prehensile requirements. The remaining three are journal articles related to frozen shoulder [1], recurrent dislocation [3], and surgical anatomy of the rotator cuff [6], three of the most common shoulder problems then and now. He documented the histologic inflammation and degeneration in various tissues including the coracohumeral ligaments, supraspinatus tendon, bursal wall, subscapularis musculotendinous junction, and biceps tendon. Thus, the problem was rather more global than localized. He emphasized, “Manipulation of frozen shoulders is a dangerous and futile procedure.” For recurrent dislocation he advocated the Magnuson procedure (transfer of the subscapularis tendon to the greater tuberosity) to create a musculotendinous sling. All but two of 23 patients he treated with this approach were satisfied with this relatively simple procedure. (Readers will note the absence of contemporary approaches to ascertain outcomes and satisfaction. The earliest outcome musculoskeletal measures were introduced in the 60s by Larson [11] and then by Harris [10], but these instruments were physician-generated and do not reflect the rather more rigorously validated patient-generated outcome measures we use today. Nonetheless, the approach used by Dr. DePalma reflected the best existing standards of reporting results.) Dr. DePalma’s classic article, “Surgical Anatomy of the Rotator Cuff and the Natural History of Degenerative Periarthritis,” [6] reflected his literature review and dissections of 96 shoulders from 50 individuals “unaware of any (shoulder) disability” and mostly over the age of 40. By the fifth decade, most specimens began to show signs of rotator cuff tearing and he found complete tears in nine specimens from “the late decades.” He concluded,
“Based on the…observations, one can reasonably construct the natural history of periarthritis of the shoulder. It is apparent that aging is an important etiological factor, and with aging certain changes take place in the connective tissue elements of the musculotendinous cuff…it is also apparent that in slowly developing lesions of this nature compensating adjustments in the mechanics of the joint take place so that severe alterations in the mechanics of the joint do not appear. However, one must admit that such a joint is very vulnerable and, if subjected to minor trauma, the existing degenerative lesion would be extended and aggravated.”
Thus, he clearly defined the benign effects of rotator cuff tear in many aging individuals, but also the potential to create substantial pain and disability.
Dr. DePalma was a prolific researcher and writer. In addition to his “Surgery of the Shoulder,” he wrote three other books, “Diseases of the Knee: Management in Medicine and Surgery” (published by J.B. Lippincott in 1954) [4], “The Management of Fractures and Dislocations” (a large and comprehensive two volume work published by W.B. Saunders in 1959, and going through 5 reprintings) [5], and “The Intervertebral Disc” (published by W.B. Saunders in 1970, and written with his colleague, Dr. Richard Rothman) [8]. PubMed lists 62 articles he published from 1948 until 1992.
We wish to pay tribute to Dr. DePalma for his vision in establishing Clinical Orthopaedics and Related Research as a unique journal and for his many contributions to orthopaedic surgery.
References
DePalma A. Loss of scapulohumeral motion (frozen shoulder). Ann Surg. 1952;135:193–204.DePalma AF. Origin and comparative anatomy of the pectoral limb. In: DePalma AF, ed. Surgery of the Shoulder. Philadelphia: JB Lippincott; 1950:1–14.DePalma AF. Recurrent dislocation of the shoulder joint. Ann Surg. 1950;132:1052–1065.DePalma AF. Diseases of the Knee: Management in Medicine and Surgery. Philadelphia, PA: JB Lippincott Company; 1954.DePalma AF. The Management of Fractures and Dislocations—An Atlas. Philadelphia: WB Saunders Company; 1959.DePalma AF. Surgical anatomy of the rotator cuff and the natural history of degenerative periarthritis. Surg Clin North Am. 1963;43:1507–1520.DePalma AF. A lifetime of devotion to the Janus of orthopedics. Bridging the gap between the clinic and laboratory. Clin Orthop Relat Res. 1991;265:146–169.DePalma AF, Rothman RH. The Intervertebral Disc. Philadelphia: WB Saunders Company; 1970.Derkash RS. History of the Association of Bone and Joint Surgeons. Clin Orthop Relat Res. 1997;337:306–309.Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am. 1969;51:737–755.Larson CB. Rating scale for hip disabilities. Clin Orthop Relat Res. 1963;31:85–93.
doi:10.1007/s11999-007-0105-3
PMCID: PMC2505210  PMID: 18264840
14.  Machine learning with naturally labeled data for identifying abbreviation definitions 
BMC Bioinformatics  2011;12(Suppl 3):S6.
Background
The rapid growth of biomedical literature requires accurate text analysis and text processing tools. Detecting abbreviations and identifying their definitions is an important component of such tools. Most existing approaches for the abbreviation definition identification task employ rule-based methods. While achieving high precision, rule-based methods are limited to the rules defined and fail to capture many uncommon definition patterns. Supervised learning techniques, which offer more flexibility in detecting abbreviation definitions, have also been applied to the problem. However, they require manually labeled training data.
Methods
In this work, we develop a machine learning algorithm for abbreviation definition identification in text which makes use of what we term naturally labeled data. Positive training examples are naturally occurring potential abbreviation-definition pairs in text. Negative training examples are generated by randomly mixing potential abbreviations with unrelated potential definitions. The machine learner is trained to distinguish between these two sets of examples. Then, the learned feature weights are used to identify the abbreviation full form. This approach does not require manually labeled training data.
Results
We evaluate the performance of our algorithm on the Ab3P, BIOADI and Medstract corpora. Our system demonstrated results that compare favourably to the existing Ab3P and BIOADI systems. We achieve an F-measure of 91.36% on Ab3P corpus, and an F-measure of 87.13% on BIOADI corpus which are superior to the results reported by Ab3P and BIOADI systems. Moreover, we outperform these systems in terms of recall, which is one of our goals.
doi:10.1186/1471-2105-12-S3-S6
PMCID: PMC3111592  PMID: 21658293
15.  Secondary Prevention of Fragility Fractures: Are We Following the Guidelines? 
INTRODUCTION
The aim of this study was to determine whether orthopaedic surgeons follow the British Orthopaedic Association (BOA) guidelines for secondary prevention of fragility fractures.
PATIENTS AND METHODS
A retrospective audit was conducted on patients with neck of femur fractures treated in our hospital between October and November 2003. A re-audit was conducted during the period August to October 2004.
RESULTS
There were 27 patients in the initial study period. Twenty-six patients (96%)had full blood count measured with LFT and bone-profile measured in 18 patients (66%). Only nine patients (30%)had treatment for osteoporosis (calcium and vitamin D). Only one patient was referred for DEXA scan. Steps were taken in the form of creating better awareness among the junior doctors and nurse practitioners of the BOA guidelines. In patients above 80 years of age, it was decided to use abbreviated mental score above 7 as a clinical criteria for DEXA referral. A hospital protocol based on BOA guidelines was made. A re-audit was conducted during the period August to October 2004. There were 37 patients. All had their full blood count and renal profile checked (100%). The bone-profile was measured in 28 (75.7%) and LFT in 34 (91.9%)patients. Twenty-four patients (65%) received treatment in the form of calcium + vitamin D (20) and bisphosphonate (4). DEXA-scan referral was not indicated in 14 patients as 4 were already on bisphosphonates and for 10 patients their abbreviated mental score was less than 7. Among the remaining 23 patients, 9 patients (40%) were referred for DEXA scan. This improvement is statistically significant (P = 0.03, chi square test).
DISCUSSION AND CONCLUSIONS
The re-audit shows that, although there is an improvement in the situation, we are still below the standards of secondary prevention of fragility fractures with 60% of femoral fragility fracture patients not being referred for DEXA scan. A pathway lead by a fracture liaison nurse dedicated to osteoporotic fracture patients should improve the situation.
doi:10.1308/003588406X116891
PMCID: PMC1964691  PMID: 17002853
Osteoporosis; Secondary prevention; Guidelines
16.  Development of a Scoring System to Evaluate the Severity of Craniocervical Spinal Cord Compression in Patients with Mucopolysaccharidosis IVA (Morquio A Syndrome) 
JIMD Reports  2013;11:65-72.
Background: As spinal cord compression at the craniocervical junction (CCJ) is a life-threatening manifestation in patients with mucopolysaccharidosis (MPS) IVA, surgical decompression should be performed before damage becomes irreversible. We evaluated the diagnostic value of several examinations for determining the need for decompression surgery.
Methods: We retrospectively analysed results of clinical neurological examination, somatosensory evoked potential (SEP) and magnetic resonance imaging (MRI) in 28 MPS IVA patients. A scoring system – based on the severity of findings – was used to compare results of patients with and without indication for decompression surgery. Individual test scores and two composite scores were evaluated for their potential to assess severity of CCJ impairment.
Results: Sixteen patients had an indication for surgery; 12 of them had undergone surgery. Twelve patients had no indication for surgery; none had received surgery. Neurological (P = 0.004), MRI (P < 0.001) and atlantoaxial subluxation (P = 0.006) scores, but not SEP and odontoid hypoplasia scores, differed significantly between patients with and without surgical indication. Both the abbreviated CCJ score, i.e. sum of neurological and MRI scores, and the extended CCJ score, i.e. sum of abbreviated CCJ and atlantoaxial subluxation score, discriminated between patients with and without surgical indication (abbreviated: 0–2 points vs 2–5 points, P < 0.001; extended: 0–3 points vs 3–7 points; P < 0.001). Although CCJ instability plays a major role in cervical cord pathology, decompression surgery without occipito-cervical stabilisation may yield good postoperative results.
Conclusions: The abbreviated and extended CCJ scores are objective, transparent and reproducible tools for assessing the CCJ pathology and the need for surgery.
doi:10.1007/8904_2013_223
PMCID: PMC3755552  PMID: 23580366
17.  Synonym extraction and abbreviation expansion with ensembles of semantic spaces 
Background
Terminologies that account for variation in language use by linking synonyms and abbreviations to their corresponding concept are important enablers of high-quality information extraction from medical texts. Due to the use of specialized sub-languages in the medical domain, manual construction of semantic resources that accurately reflect language use is both costly and challenging, often resulting in low coverage. Although models of distributional semantics applied to large corpora provide a potential means of supporting development of such resources, their ability to isolate synonymy from other semantic relations is limited. Their application in the clinical domain has also only recently begun to be explored. Combining distributional models and applying them to different types of corpora may lead to enhanced performance on the tasks of automatically extracting synonyms and abbreviation-expansion pairs.
Results
A combination of two distributional models – Random Indexing and Random Permutation – employed in conjunction with a single corpus outperforms using either of the models in isolation. Furthermore, combining semantic spaces induced from different types of corpora – a corpus of clinical text and a corpus of medical journal articles – further improves results, outperforming a combination of semantic spaces induced from a single source, as well as a single semantic space induced from the conjoint corpus. A combination strategy that simply sums the cosine similarity scores of candidate terms is generally the most profitable out of the ones explored. Finally, applying simple post-processing filtering rules yields substantial performance gains on the tasks of extracting abbreviation-expansion pairs, but not synonyms. The best results, measured as recall in a list of ten candidate terms, for the three tasks are: 0.39 for abbreviations to long forms, 0.33 for long forms to abbreviations, and 0.47 for synonyms.
Conclusions
This study demonstrates that ensembles of semantic spaces can yield improved performance on the tasks of automatically extracting synonyms and abbreviation-expansion pairs. This notion, which merits further exploration, allows different distributional models – with different model parameters – and different types of corpora to be combined, potentially allowing enhanced performance to be obtained on a wide range of natural language processing tasks.
doi:10.1186/2041-1480-5-6
PMCID: PMC3937097  PMID: 24499679
18.  Airway Clearance Devices for Cystic Fibrosis 
Executive Summary
Objective
The purpose of this evidence-based analysis is to examine the safety and efficacy of airway clearance devices (ACDs) for cystic fibrosis and attempt to differentiate between devices, where possible, on grounds of clinical efficacy, quality of life, safety and/or patient preference.
Background
Cystic fibrosis (CF) is a common, inherited, life-limiting disease that affects multiple systems of the human body. Respiratory dysfunction is the primary complication and leading cause of death due to CF. CF causes abnormal mucus secretion in the airways, leading to airway obstruction and mucus plugging, which in turn can lead to bacterial infection and further mucous production. Over time, this almost cyclical process contributes to severe airway damage and loss of respiratory function. Removal of airway secretions, termed airway clearance, is thus an integral component of the management of CF.
A variety of methods are available for airway clearance, some requiring mechanical devices, others physical manipulation of the body (e.g. physiotherapy). Conventional chest physiotherapy (CCPT), through the assistance of a caregiver, is the current standard of care for achieving airway clearance, particularly in young patients up to the ages of six or seven. CF patients are, however, living much longer now than in decades past. The median age of survival in Canada has risen to 37.0 years for the period of 1998-2002 (5-year window), up from 22.8 years for the 5-year window ending in 1977. The prevalence has also risen accordingly, last recorded as 3,453 in Canada in 2002, up from 1,630 in 1977. With individuals living longer, there is a greater need for independent methods of airway clearance.
Airway Clearance Devices
There are at least three classes of airway clearance devices: positive expiratory pressure devices (PEP), airway oscillating devices (AOD; either handheld or stationary) and high frequency chest compression (HFCC)/mechanical percussion (MP) devices. Within these classes are numerous different brands of devices from various manufacturers, each with subtle iterations. At least 10 devices are licensed by Health Canada (ranging from Class 1 to Class 3 devices).
Evidence-Based Analysis of Effectiveness
Research Questions
Does long-term use of ACDs improve outcomes of interest in comparison to CCPT in patients with CF?
Does long-term use of one class of ACD improve outcomes of interest in comparison to another class of ACD in CF patients?
Literature Search
A comprehensive literature search was performed on March 7, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1950 to March 7, 2009.
Inclusion Criteria
All randomized controlled trials including those of parallel and crossover design,
Systematic reviews and/or meta-analyses. Randomized controlled trials (RCTs), systematic reviews and meta-analyses
Exclusion Criteria
Abstracts were generally excluded because their methods could not be examined; however, abstract data was included in several Cochrane meta-analyses presented in this paper;
Studies of less than seven days duration (including single treatment studies);
Studies that did not report primary outcomes;
Studies in which less than 10 patients completed the study.
Outcomes of Interest
Primary outcomes under review were percent-predicted forced expiratory volume (FEV-1), forced vital capacity (FVC), and forced expiratory flow between 25%-75% (FEF25-75). Secondary outcomes included number of hospitalizations, adherence, patient preference, quality of life and adverse events. All outcomes were decided a priori.
Summary of Findings
Literature searching and back-searching identified 13 RCTs meeting the inclusion criteria, along with three Cochrane systematic reviews. The Cochrane reviews were identified in preliminary searching and used as the basis for formulating this review. Results were subgrouped by comparison and according to the available literature. For example, results from Cochrane meta-analyses included abstract data and therefore, additional meta-analyses were also performed on trials reported as full publications only (MAS generally excludes abstracted data when full publications are available as the methodological quality of trials reported in abstract cannot be properly assessed).
Executive Summary Table 1 summarizes the results across all comparisons and subgroupings for primary outcomes of pulmonary function. Only two comparisons yielded evidence of moderate or high quality according to GRADE criteria–the comparisons of CCPT vs. PEP and handheld AOD vs. PEP–but only the comparison of CCPT vs. PEP noted a significant difference between treatment groups. In comparison to CCPT, there was a significant difference in favour of PEP for % predicted FEV-1 and FVC according to one long-term, parallel RCT. This trial was accepted as the best available evidence for the comparison. The body of evidence for the remaining comparisons was low to very low, according to GRADE criteria, being downgraded most often because of poor methodological quality and low generalizability. Specifically, trials were likely not adequately powered (low sample sizes), did not conduct intention-to-treat analyses, were conducted primarily in children and young adolescents, and outdated (conducted more than 10 years ago).
Secondary outcomes were poorly or inconsistently reported, and were generally not of value to decision-making. Of note, there were a significantly higher number of hospitalizations among participants undergoing AOD therapy in comparison to PEP therapy.
Summarization of results for primary outcomes by comparison and subgroupings
Bolding indicates significant difference
Positive summary statistics favour the former intervention
Abbreviations: AOD, airway oscillating device; CCPT, conventional chest physiotherapy; CI, confidence interval; HFCC, high frequency chest compression; MP, mechanical percussion; N/A: not applicable; PEP, positive expiratory pressure
Economic Analysis
Devices ranged in cost from around $60 for PEP and handheld AODs to upwards of $18,000 for a HFCC vest device. Although the majority of device costs are paid out-of-pocket by the patients themselves, their parents, or covered by third-party medical insurance, Ontario did provide funding assistance through the Assistive Devices Program (ADP) for postural drainage boards and MP devices. These technologies, however, are either obsolete or their clinical efficacy is not supported by evidence. ADP provided roughly $16,000 in funding for the 2008/09 fiscal year. Using device costs and prevalent and incident cases of CF in Ontario, budget impact projections were generated for Ontario. Prevalence of CF in Ontario for patients from ages 6 to 71 was cited as 1,047 cases in 2002 while incidence was estimated at 46 new cases of CF diagnosed per year in 2002. Budget impact projections indicated that PEP and handheld AODs were highly economically feasible costing around $90,000 for the entire prevalent population and less than $3,000 per year to cover new incident cases. HFCC vest devices were by far the most expensive, costing in excess of $19 million to cover the prevalent population alone.
Conclusions
There is currently a lack of sufficiently powered, long-term, parallel randomized controlled trials investigating the use of ACDs in comparison to other airway clearance techniques. While much of the current evidence suggests no significant difference between various ACDs and alternative therapies/technologies, at least according to outcomes of pulmonary function, there is a strong possibility that past trials were not sufficiently powered to identify a difference. Unfortunately, it is unlikely that there will be any future trials comparing ACDs to CCPT as withholding therapy using an ACD may be seen as unethical at present.
Conclusions of clinical effectiveness are as follows:
Moderate quality evidence suggests that PEP is at least as effective as or more effective than CCPT, according to primary outcomes of pulmonary function.
Moderate quality evidence suggests that there is no significant difference between PEP and handheld AODs, according to primary outcomes of pulmonary function; however, secondary outcomes may favour PEP.
Low quality evidence suggests that there is no significant difference between AODs or HFCC/MP and CCPT, according to both primary and secondary outcomes.
Very low quality evidence suggests that there is no significant difference between handheld AOD and CCPT, according to primary outcomes of pulmonary function.
Budget impact projections show PEP and handheld AODs to be highly economically feasible.
PMCID: PMC3377547  PMID: 23074531
19.  Mutation of von Hippel–Lindau Tumour Suppressor and Human Cardiopulmonary Physiology 
PLoS Medicine  2006;3(7):e290.
Background
The von Hippel–Lindau tumour suppressor protein–hypoxia-inducible factor (VHL–HIF) pathway has attracted widespread medical interest as a transcriptional system controlling cellular responses to hypoxia, yet insights into its role in systemic human physiology remain limited. Chuvash polycythaemia has recently been defined as a new form of VHL-associated disease, distinct from the classical VHL-associated inherited cancer syndrome, in which germline homozygosity for a hypomorphic VHL allele causes a generalised abnormality in VHL–HIF signalling. Affected individuals thus provide a unique opportunity to explore the integrative physiology of this signalling pathway. This study investigated patients with Chuvash polycythaemia in order to analyse the role of the VHL–HIF pathway in systemic human cardiopulmonary physiology.
Methods and Findings
Twelve participants, three with Chuvash polycythaemia and nine controls, were studied at baseline and during hypoxia. Participants breathed through a mouthpiece, and pulmonary ventilation was measured while pulmonary vascular tone was assessed echocardiographically. Individuals with Chuvash polycythaemia were found to have striking abnormalities in respiratory and pulmonary vascular regulation. Basal ventilation and pulmonary vascular tone were elevated, and ventilatory, pulmonary vasoconstrictive, and heart rate responses to acute hypoxia were greatly increased.
Conclusions
The features observed in this small group of patients with Chuvash polycythaemia are highly characteristic of those associated with acclimatisation to the hypoxia of high altitude. More generally, the phenotype associated with Chuvash polycythaemia demonstrates that VHL plays a major role in the underlying calibration and homeostasis of the respiratory and cardiovascular systems, most likely through its central role in the regulation of HIF.
Editors' Summary
Background.
Human cells (like those of other multicellular animals) use oxygen to provide the energy needed for daily life. Having not enough oxygen is a problem, but having too much is also dangerous because it damages proteins, DNA, and other large molecules that keep cells functioning. Consequently, the physiological systems—including the heart, lungs, and circulation—work together to balance oxygen supply and demand throughout the body. When oxygen is limiting (a condition called hypoxia), as happens at high altitudes, the cellular oxygen supply is maintained by increasing the heart rate, increasing the speed and depth of breathing (hyperventilation), constricting the blood vessels in the lung (pulmonary vasoconstriction), and increasing the number of oxygen-carrying cells in the blood. All these physiological changes increase the amount of oxygen that can be absorbed from the air, but how they are regulated is poorly understood. By contrast, researchers know quite a bit about how individual cells respond to hypoxia. When oxygen is limited, a protein called hypoxia-inducible factor (or HIF) activates a number of target proteins that help the cell get enough oxygen (for example, proteins that stimulate the growth of new blood vessels). When there is plenty of oxygen, another protein, called von Hippel–Lindau tumor suppressor (abbreviated VHL), rapidly destroys HIF. Recently, researchers discovered that a genetic condition called Chuvash polycythaemia, characterised by the overproduction of red blood cells, is caused by a specific defect in VHL that reduces its ability to destroy HIF. As a result, the expression of certain HIF target proteins is increased even when oxygen levels are normal.
Why Was This Study Done?
Chuvash polycythaemia is very rare, and so far little is known about how this genetic abnormality affects the physiology and long-term health of patients. By studying heart and lung function in patients with Chuvash polycythaemia, the researchers involved in this study hoped to discover more about the health consequences of the condition and to find out whether the VHL–HIF system controls systemic responses to hypoxia as well as cellular responses.
What Did the Researchers Do and Find?
The researchers recruited and studied three patients with Chuvash polycythaemia, and, as controls for the comparison, several normal individuals and patients with an unrelated form of polycythaemia. They then measured how the lungs and hearts of these people reacted to mild hypoxia (similar to that experienced on commercial air flights) and moderate hypoxia (equiv alent to being on the top of an Alpine peak). They found that patients with Chuvash polycythaemia naturally breathe slightly quicker and deeper than normal individuals, and that their breathing rate increased dramatically and abnormally when oxygen was reduced. They also found that at normal oxygen levels the pulmonary blood vessels of these patients were more constricted than those of control individuals, and that they reacted more extremely to hypoxia. Similarly, the normal heart rate of the patients was slightly higher than that of the controls and increased much more in response to mild hypoxia.
What Do These Findings Mean?
The physiological differences measured by the researchers between Chuvash polycythaemia patients and control individuals are similar to the adaptations seen in people traveling to high altitudes where oxygen is limited. Thus, the VHL–HIF proteins may regulate the response to different oxygen concentrations both in individual cells and at the systemic level, although more physiological studies are needed to confirm this. Because the pulmonary blood vessels of patients with Chuvash polycythaemia are always abnormally constricted, and even more so when oxygen is limited, these people should avoid living at high altitude and should minimise air travel, suggest the researchers. The increased blood pressure in their lungs (pulmonary hypertension) could conceivably cause heart failure under such circumstances. Finally, this study has implications for the development of drugs directed at the VHL–HIF system. Agents are currently being designed to promote the development of new blood vessels after strokes or heart attacks by preventing the destruction of HIF, but based on the findings here such agents might have undesirable physiological affects. Conversely, HIF inhibitors (which act as anti-cancer reagents by increasing hypoxia in the centre of tumors and so inhibiting their growth) might be useful in the treatment of pulmonary hypertension.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030290.
• Online Mendelian Inheritance in Man page on Chuvash polycythaemia
• Information from the VHL Family Alliance on von Hippel–Lindau disease, including information on Chuvash polycythaemia
• Wikipedia page on polycythaemia and von Hippel–Lindau disease (note: Wikipedia is a free online encyclopaedia that anyone can edit)
Physiological study of patients with Chuvash polycythemia (caused by mutation of VHL) reveals characteristics similar to those associated with acclimatization to the hypoxia of high altitude.
doi:10.1371/journal.pmed.0030290
PMCID: PMC1479389  PMID: 16768548
20.  P24 - Geriatric Medicine: An Innovative Care Strategy in Orthopaedics and Traumatology 
For many years, the administration of the Careggi University Hospital (CUH), in agreement with the Faculty of Medicine and Surgery of the University of Florence, has pressed for the creation of a department of general medicine within its othopaedic traumatology centre. In its decision n.243 of May 5, 2009, the administration of the CUH, along the lines of similar experiences already in place, set up a simple departmental unit (SDU) of geriatric medicine (GM) within the hospital’s department of orthopaedics.
The aim of this unit is to guarantee continuity of care to orthopaedics inpatients, through the identification of a specific care pathway for clinically unstable patients. The clinical activity carried out, mainly in the context of the provision of continuity of care, takes the form of daily consultancy. The SDU has a series of objectives, organisational (less postponement of surgery due to medical problems, better integration of healthcare through a multidisciplinary team, provision of internal medicine and geriatric consultancy to guarantee continuity of care), clinical (reduction of peri-operative medical complications and adverse events) and strategic (improvement of the quality of geriatric and internal medicine care, better communication with patients and families). The unit strives to exploit to the full the multi-professional (doctors, rehabilitation therapists, registered nurses, social workers) and interdisciplinary (internal medicine, geriatrics, orthopaedics, physical medicine, anaesthesiology, cardiology, angiology etc.) intervention and, in the fragile elderly, applies a multi-dimensional geriatric assessment instrument.
Clinical activity:
The physicians working in the GM SDU provide daily consultancy, including Saturday mornings. Constant telephone contact is available, also on Sundays and holidays.
In the period from 1/9/2009 to 31/7/2010, a total of 1867 consultancies were provided, spread over 268 days, which corresponds to a mean of 6.97 examinations/day. Of these, 652 (34.92%) were first visits and 1215 (65.08%) were follow ups. The assessments were always conducted in a spirit of multi-professional and multidisciplinary collaboration.
The assessments were carried out in the following departments: general orthopaedics II (25.98%), general orthopaedics I (21.26%), general orthopaedics III (18.26%), traumatology-orthopaedics (13.55%), orthopaedic oncology and reconstruction (11.25%) as well as, in smaller percentages, in all the other SDUs of the orthopaedics department, in the neurosurgery department, the plastic surgery department and the spinal unit.
In particular, internal and geriatric medicine consultancy for patients was requested in connection with high levels of co-morbidity, polypharmacy regimens, acute confusional state, dehydration, hydro-electrolytic disorders, uncompensated type 2 diabetes mellitus, pulmonary embolism, chronic liver disease and cirrhosis, pneumonia and bronchitis causing respiratory insufficiency, decompensated congestive heart failure, targeted antibiotic therapy, chronic renal insufficiency, and management of anti-aggregant and anticoagulant therapies.
Positive aspects: the clinical assessments were made using a multidisciplinary approach, based on the fundamental collaboration of specialists in orthopaedics, anaesthesiology-resuscitation, angiology, cardiology, radiology and physical medicine; excellent collaboration with services (radiology, neuroradiology, angiology, cardiology, etc.).
Negative aspects: constant difficulties transferring clinically unstable patients to the hospital’s medical specialty SDUs due to lack of beds; lack of intermediate care beds as a sort of “buffer” between the intensive care and inpatient departments; scope for improving the internal medicine skills of the nursing staff.
Research projects:
In synergy the hospital’s other SDUs, the GM SDU takes part in projects aiming to improve care and clinical management. It currently has collaborations with the geriatrics clinic, regional centre of reference for haemostasis and thrombosis, the bone metabolism clinic, the orthopaedics clinics, the geriatrics agency, the radiology service, the continuity-of-care agency, the clinical management, and the general affairs unit. Furthermore, on the instigation of the regional health council, a working group has recently been set up on the reorganisation of the “Care pathway of elderly patients with proximal femur fracture (orthogeriatrics)”.
Prospects for implementation and improvement:
The aims of the “Project to reorganise and upgrade the orthopaedics and traumatology centre of the Careggi University Hospital” include: the institution of a medical geriatrics department providing medium and high intensity of care; the presence, 24 hours/day, of a specialist from the medical area in the traumatology open space; the involvement of the internal medicine specialist in pre-hospitalisation procedures.
PMCID: PMC3213796
21.  Optimum Methadone Compliance Testing 
Executive Summary
Objective
The objective of this analysis was to determine the diagnostic utility of oral fluid testing collected with the Intercept oral fluid collection device.
Clinical Need: Target Population and Condition
Opioids (opiates or narcotics) are a class of drugs derived from the opium poppy plant that typically relieve pain and produce a euphoric feeling. Methadone is a long-acting synthetic opioid used to treat opioid dependence and chronic pain. It prevents symptoms of opioid withdrawal, reduces opioid cravings and blocks the euphoric effects of short-acting opioids such as heroin and morphine. Opioid dependence is associated with harms including an increased risk of exposure to Human Immunodeficiency Virus and Hepatitis C as well as other health, social and psychological crises. The goal of methadone treatment is harm reduction. Treatment with methadone for opioid dependence is often a long-term therapy. The Ontario College of Physicians and Surgeons estimates that there are currently 250 physicians qualified to prescribe methadone, and 15,500 people in methadone maintenance programs across Ontario.
Drug testing is a clinical tool whose purpose is to provide objective meaningful information, which will reinforce positive behavioral changes in patients and guide further treatment needs. Such information includes knowledge of whether the patient is taking their methadone as prescribed and reducing or abstaining from using opioid and other drugs of abuse use. The results of drug testing can be used with behavior modification techniques (contingency management techniques) where positive reinforcements such as increased methadone take-home privileges, sustained employment or parole are granted for drug screens negative for opioid use, and negative reinforcement including loss of these privileges for drug screens positive for opioid used.
Body fluids including blood, oral fluid, often referred to as saliva, and urine may contain metabolites and the parent drug of both methadone and drugs of abuse and provide a means for drug testing. Compared with blood which has a widow of detection of several hours, urine has a wider window of detection, approximately 1 to 3 days, and is therefore considered more useful than blood for drug testing. Because of this, and the fact that obtaining a urine specimen is relatively easy, urine drug screening is considered the criterion measure (gold standard) for methadone maintenance monitoring. However, 2 main concerns exist with urine specimens: the possibility of sample tampering by the patient and the necessity for observed urine collection. Urine specimens may be tampered with in 3 ways: dilution, adulteration (contamination) with chemicals, and substitution (patient submits another persons urine specimen). To circumvent sample tampering the supervised collection of urine specimens is a common and recommended practice. However, it has been suggested that this practice may have negative effects including humiliation experienced by patient and staff, and may discourage patients from staying in treatment. Supervised urine specimen collection may also present an operational problem as staff must be available to provide same-sex supervision. Oral fluid testing has been proposed as a replacement for urine because it can be collected easily under direct supervision without infringement of privacy and reduces the likelihood of sample tampering. Generally, the results of oral fluid drug testing are similar to urine drug testing but there are some differences, such as lower concentrations of substances in oral fluid than urine, and some drugs remain detectable for longer periods of time in urine than oral fluid.
The Technology Being Reviewed
The Intercept Oral Specimen Collection Device (Ora-Sure Technologies, Bethlehem, PA) consists of an absorbent pad mounted on a plastic stick. The pad is coated with common salts. The absorbent pad is inserted into the mouth and placed between the cheek and gums for 3 minutes on average. The pad absorbs the oral fluid. After 3 minutes (range 2min-5 min) the collection device is removed from the mouth and the absorbent pad is placed in a small vial which contains 0.8mL of pH-balanced preservative, for transportation to a laboratory for analysis. It is recommended that the person undergoing oral fluid drug testing have nothing to eat or drink for a 10- minute period before the oral fluid specimen is collected. This will remove opportunity for adulteration. Likewise, it is recommended that the person be observed for the duration of the collection period to prevent adulteration of the specimen. An average of 0.4 mL of saliva can be collected. The specimen may be stored at 4C to 37C and tested within 21 days of collection (or within 6 weeks if frozen).
The oral fluid specimen must be analyzed in a laboratory setting. There is no point-of-care (POC) oral fluid test kit for drugs of abuse (other than for alcohol). In the laboratory the oral fluid is extracted from the vial after centrifugation and a screening test is completed to eliminate negative specimens. Similar to urinalysis, oral fluid specimens are analyzed first by enzyme immunoassay with positive specimens sent for confirmatory testing. Comparable cut-off values to urinalysis by enzyme immunoassay have been developed for oral fluids
Review Strategy
 
Research Question
What is the diagnostic utility of the Intercept oral specimen device?
Inclusion criteria:
Studies evaluating paired urine and oral fluid specimens from the same individual with the Intercept oral fluid collection device.
The population studied includes drug users.
Exclusion criteria:
Studies testing for marijuana (THC) only.
Outcomes:
Sensitivity and Specificity of oral fluid testing compared to urinalysis for methadone (methadone metabolite), opiates, cocaine, benzodiazepines, and alcohol.
Quality of the Body of Evidence
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of the body of evidence (defined as 1 or more studies) supporting the research questions explored in this systematic review. A description of the GRADE system is reported in Appendix 1.
Summary of Findings
A total of 854 potential citations were retrieved. After reviewing titles and abstracts, 2 met the inclusion and exclusion criteria. Two other relevant studies were found after corresponding with the author of the 2 studies retrieved from the literature search. Therefore a total of 4 published studies are included in this analysis. All 4 studies carried out by the same investigator meet the definition of Medical Advisory Secretariat level III (not a-randomized controlled trial with contemporaneous controls) study design. In each of the studies, paired urine and oral fluid specimens where obtained from drug users. Urine collection was not observed in the studies however, laboratory tests for pH and creatinine were used to determine the reliability of the specimen. Urine specimens thought to be diluted and unreliable were removed from the evaluation. Urinalysis was used as the criterion measurement for which to determine the sensitivity and specificity of oral fluid testing by the Intercept oral fluid device for opiates, benzodiazepines, cocaine and marijuana. Alcohol was not tested in any of the 4 studies. From these 4 studies, the following conclusions were drawn:
The evidence indicates that oral fluid testing with the Intercept oral fluid device has better specificity than sensitivity for opiates, benzodiazepines, cocaine and marijuana.
The sensitivity of oral fluids testing with the Intercept oral fluid device seems to be from best to worst: cocaine > benzodiazepines >opiates> marijuana.
The sensitivity and specificity for opiates of the Intercept oral fluid device ranges from 75 to 90% and 97- 100% respectively.
The consequences of opiate false-negatives by oral fluid testing with the Intercept oral fluid device need to be weighed against the disadvantages of urine testing, including invasion of privacy issues and adulteration and substitution of the urine specimen.
The window of detection is narrower for oral fluid drug testing than urinalysis and because of this oral fluid testing may best be applied in situations where there is suspected frequent drug use. When drug use is thought to be less frequent or remote, urinalysis may offer a wider (24-48 hours more than oral fluids) window of detection.
The narrow window of detection for oral fluid testing may mean more frequent testing is needed compared to urinalysis. This may increase the expense for drug testing in general.
POC oral fluid testing is not yet available and may limit the practical utility of this drug testing methodology. POC urinalysis by immunoassay is available.
The possible applications of oral fluid testing may include:
Because of its narrow window of detection compared to urinalysis oral fluid testing may best be used during periods of suspected frequent or recent drug use (within 24 hours of drug testing). This is not to say that oral fluid testing is superior to urinalysis during these time periods.
In situations where an observed urine specimen is difficult to obtain. This may include persons with “shy bladder syndrome” or with other urinary conditions limiting their ability to provide an observed urine specimen.
When the health of the patient would make urine testing unreliable (e,g., renal disease)
As an alternative drug testing method when urine specimen tampering practices are suspected to be affecting the reliability of the urinalysis test.
Possible limiting Factors to Diffusion of Oral Fluid Technology
No oral fluid POC test equivalent to onsite urine dips or POC analyzer reducing immediacy of results for patient care.
Currently, physicians get reimbursed directly for POC urinalysis. Oral fluid must be analyzed in a lab setting removing physician reimbursement, which is a source of program funding for many methadone clinics.
Small amount of oral fluid specimen obtained; repeat testing on same sample will be difficult.
Reliability of positive oral fluid methadone (parent drug) results may decrease because of possible contamination of oral cavity after ingestion of dose. Therefore high methadone levels may not be indicative of compliance with treatment. Oral fluid does not as yet test for methadone metabolite.
There currently is no licensed provincial laboratory that analyses oral fluid specimens.
Abbreviations
2-ethylidene- 1,5-dimethyl-3,3-diphenylpyrrolidine
enzyme immunoassay
Enzyme Linked Immunosorbent Assay (ELISA),
Enzyme Multiplied Immunoassay Test (EMIT)
Gas chromatography
gas chromatography/mass spectrometry
High-performance liquid chromatography
Limit of Detection
Mass spectrometry
Methadone Maintenance Treatment
Oral fluid testing
Phencyclidine
Point of Care Testing
tetrahydrocannabinol
11-nor-delta-9-tetrhydrocannabinol-9-carboxylic acid
urine drug testing
PMCID: PMC3379523  PMID: 23074492
22.  Clinical and Experimental Observations with Regard to the Injection of Certain Agents (Pregl’s Solution) into Chronic Arthritic Joints 
J.E.M. (Tommy) Thomson was born in Los Angeles, California in 1989, of “pious and scholarly” parents with “evangelistic...interests” [3]. His grandfather had been a missionary bishop in the Methodist Church. He attended Evanston Academy and then Northwestern University. While he began his medical studies at Texas Christian College, he completed his medical education at Rush Medical College in 1915. He took an internship in Chicago, where his mentors reportedly included Drs. Edwin Ryerson (first President of the AAOS), John Ridlon, and Dallas Phemister [3]. In 1916 he began medical practice with H. Winnett Orr in Lincoln, Nebraska. During WW I he served in the University of Nebraska Overseas Base Hospital No. 49. He returned to practice after the war in 1919 and remained in Lincoln during his professional life. In addition to his professional interests, he and his wife shared an interest in cattle breeding and for a while had extensive ranching interests in Nebraska. The last few years of his life were spent in semiretirement in Rancho Santa Fe, California.
Dr. Thomson traveled widely and made many friends worldwide. In 1955 he took a trip around the world but he had many other travels and was an honorary member of a number of foreign orthopaedic societies including the Czechoslovakian Orthopaedic Society, The Polish Orthopaedic and Trauma Society, the Finnish Orthopaedic Association, and the Latin American Society of Orthopaedics and Traumatology. Dr. Thomson traveled to all continents except Australia. He was a founding member of the Orthopaedic Research society. As with a number of the early offices of the AAOS, Dr. Thomson was active in the American Orthopaedic Association and the Clinical Orthopaedic Society and served as President of the latter in 1936. The Instructional Course Lectures were evidently his “brainchild” [3]. The record is unclear of the beginnings, although they evidently arose out of motion picture exhibits. What is clear is the first Instructional Course Lectures were presented in 1942 and published in 1943 with Dr. Thomson as editor. At the 1946 annual meeting, Dr. Thomson was selected to “establish and monitor the Instructional Course Lectures” [2]. He continued to serve as editor of the published Instructional Course Lectures until 1948. One account suggests the idea of a central office was his, and that he personally furnished a temporary central office in Lincoln until permanent headquarters could be established [1]. He was a man of great energy and bearing. In his Presidential Lecture he commented, “There is an old saying – you can’t make a silk purse out of a pig’s ear. I sometimes feel that in our post-war fervor, in behalf of the veterans separated from military service, we tend to encourage some conscientious young men to enter a field of training for which they are totally unsuited.” Despite infirmities in his last years (he had bilateral hip prostheses), he continued to be active, and died while giving lectures at the University of Kansas (“as he would have wished ‘with his boots on.’” [3]).
The article we reprint here reflects Thomson’s innovative thinking. Surgical alternatives for chronic arthritis were not well developed in 1932 and Thomson explored a method described by Pregl of Vienna [4]. Pregl injected a “secret preparation” that was a “non-irritating, non-staining, watery solution of free and combined iodine with certain idodides.” Thomson described his own similar solution, and used two to five injections spaced five to seven days apart. He reported the results in 15 patients, most with undefined or posttraumatic arthritis, but one with gonorrheal and one with likely acute joint sepsis, and two with bursitis (olecranon and prepatellar). He further produced experimental arthritis in four rabbits by injection of microbes or a dilute carbolic acid solution. Two to four weeks later, he injected Pregl’s solution and noted resolution. His observations, he concluded, warranted “further investigation and a more general use of Pregl’s solution in treating chronic effusion of arthritic and traumatized joints.” J.E.M. Thomson, MD is shown. Photograph is reproduced with permission and ©American Academy of Orthopaedic Surgeons. Fifty Years of Progress, 1983.
References
Heck CV. Commemorative Volume 1933–1983 Fifty Years of Progress. Chicago, IL: American Academy of Orthopaedic Surgeons; 1983.Heck CV. Fifty Years of Progress: In Recognition of the 50th Anniversary of the American Academy of Orthopaedic Surgeons. Chicago, IL: American Academy of Orthopaedic Surgeons; 1983.James E. M. Thomson 1889–1962. J Bone Joint Surg Am. 1963;45:206–208.Thomson JEM. Clinical and experimental observations with regard to the injection of certain agents (Pregl's solution) into chronic arthritic joints. J Bone Joint Surg Am. 1933;15:483–490.
doi:10.1007/s11999-007-0012-7
PMCID: PMC2505292  PMID: 18196381
23.  Thromboprophylaxis in spinal surgery: a survey 
Background
Venous Thromboembolism (VTE) is the most common complication following major joint surgery. While attention has been focused upon the incidence of thromboembolic disease following total hip or knee arthroplasty or emergency surgery for hip fracture, there exists a gap in the medical literature examining the incidence of VTE in spinal surgery. Evidence suggests that the prevalence of DVT after spinal surgery is higher than generally recognized but with a shortage of epidemiological data, guidelines for optimal prophylaxis are limited. This survey, of individuals attending the 2009 British Association of Spinal Surgeons Annual Meeting, sought to examine prevailing trends in VTE thromboprophylaxis in spinal surgery, adherence to guideline outlined by the National Institute for Health and Clinical Excellence (NICE) and to compare selections made by orthopaedic and neurosurgeons.
Methods
We developed a questionnaire with eight clinical scenarios. Participants were asked to supply details on their specialty and to select which method(s) of thromboprophylaxis they would employ for each scenario. Chi squared analysis was used for statistical comparison of the questionnaire responses.
Results
73% of neurosurgical respondents' and 31% of orthopaedic surgeons employed low molecular weight heparin (p < 0.001). Neurosurgeons also selected anti-embolism stockings more frequently (79% v 50%) while orthopaedic surgeons preferred mechanical prophylaxis (26% v 9%). There was no significant difference between trauma and non-trauma scenarios (p = 0.05).
Conclusion
There is no clear consensus in thromboprophylaxis in spinal surgery. There was a significant difference in selections across surgical disciplines with neurosurgeons more closely adhering to national guidelines. Further research examining the epidemiology of venous thromboembolism in spinal surgery and the risks-benefit relationship of thromboprophylaxis is warranted.
doi:10.1186/1749-799X-7-14
PMCID: PMC3349591  PMID: 22458927
Spinal surgery; Venous thromboembolism; Thromboprophylaxis; Orthopaedic surgery; Neurosurgery
24.  Exploiting MeSH indexing in MEDLINE to generate a data set for word sense disambiguation 
BMC Bioinformatics  2011;12:223.
Background
Evaluation of Word Sense Disambiguation (WSD) methods in the biomedical domain is difficult because the available resources are either too small or too focused on specific types of entities (e.g. diseases or genes). We present a method that can be used to automatically develop a WSD test collection using the Unified Medical Language System (UMLS) Metathesaurus and the manual MeSH indexing of MEDLINE. We demonstrate the use of this method by developing such a data set, called MSH WSD.
Methods
In our method, the Metathesaurus is first screened to identify ambiguous terms whose possible senses consist of two or more MeSH headings. We then use each ambiguous term and its corresponding MeSH heading to extract MEDLINE citations where the term and only one of the MeSH headings co-occur. The term found in the MEDLINE citation is automatically assigned the UMLS CUI linked to the MeSH heading. Each instance has been assigned a UMLS Concept Unique Identifier (CUI). We compare the characteristics of the MSH WSD data set to the previously existing NLM WSD data set.
Results
The resulting MSH WSD data set consists of 106 ambiguous abbreviations, 88 ambiguous terms and 9 which are a combination of both, for a total of 203 ambiguous entities. For each ambiguous term/abbreviation, the data set contains a maximum of 100 instances per sense obtained from MEDLINE.
We evaluated the reliability of the MSH WSD data set using existing knowledge-based methods and compared their performance to that of the results previously obtained by these algorithms on the pre-existing data set, NLM WSD. We show that the knowledge-based methods achieve different results but keep their relative performance except for the Journal Descriptor Indexing (JDI) method, whose performance is below the other methods.
Conclusions
The MSH WSD data set allows the evaluation of WSD algorithms in the biomedical domain. Compared to previously existing data sets, MSH WSD contains a larger number of biomedical terms/abbreviations and covers the largest set of UMLS Semantic Types. Furthermore, the MSH WSD data set has been generated automatically reusing already existing annotations and, therefore, can be regenerated from subsequent UMLS versions.
doi:10.1186/1471-2105-12-223
PMCID: PMC3123611  PMID: 21635749
25.  Machine learning and word sense disambiguation in the biomedical domain: design and evaluation issues 
BMC Bioinformatics  2006;7:334.
Background
Word sense disambiguation (WSD) is critical in the biomedical domain for improving the precision of natural language processing (NLP), text mining, and information retrieval systems because ambiguous words negatively impact accurate access to literature containing biomolecular entities, such as genes, proteins, cells, diseases, and other important entities. Automated techniques have been developed that address the WSD problem for a number of text processing situations, but the problem is still a challenging one. Supervised WSD machine learning (ML) methods have been applied in the biomedical domain and have shown promising results, but the results typically incorporate a number of confounding factors, and it is problematic to truly understand the effectiveness and generalizability of the methods because these factors interact with each other and affect the final results. Thus, there is a need to explicitly address the factors and to systematically quantify their effects on performance.
Results
Experiments were designed to measure the effect of "sample size" (i.e. size of the datasets), "sense distribution" (i.e. the distribution of the different meanings of the ambiguous word) and "degree of difficulty" (i.e. the measure of the distances between the meanings of the senses of an ambiguous word) on the performance of WSD classifiers. Support Vector Machine (SVM) classifiers were applied to an automatically generated data set containing four ambiguous biomedical abbreviations: BPD, BSA, PCA, and RSV, which were chosen because of varying degrees of differences in their respective senses. Results showed that: 1) increasing the sample size generally reduced the error rate, but this was limited mainly to well-separated senses (i.e. cases where the distances between the senses were large); in difficult cases an unusually large increase in sample size was needed to increase performance slightly, which was impractical, 2) the sense distribution did not have an effect on performance when the senses were separable, 3) when there was a majority sense of over 90%, the WSD classifier was not better than use of the simple majority sense, 4) error rates were proportional to the similarity of senses, and 5) there was no statistical difference between results when using a 5-fold or 10-fold cross-validation method. Other issues that impact performance are also enumerated.
Conclusion
Several different independent aspects affect performance when using ML techniques for WSD. We found that combining them into one single result obscures understanding of the underlying methods. Although we studied only four abbreviations, we utilized a well-established statistical method that guarantees the results are likely to be generalizable for abbreviations with similar characteristics. The results of our experiments show that in order to understand the performance of these ML methods it is critical that papers report on the baseline performance, the distribution and sample size of the senses in the datasets, and the standard deviation or confidence intervals. In addition, papers should also characterize the difficulty of the WSD task, the WSD situations addressed and not addressed, as well as the ML methods and features used. This should lead to an improved understanding of the generalizablility and the limitations of the methodology.
doi:10.1186/1471-2105-7-334
PMCID: PMC1550263  PMID: 16822321

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