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1.  Harmonization of malaria rapid diagnostic tests: best practices in labelling including instructions for use 
Malaria Journal  2014;13(1):505.
Rapid diagnostic tests (RDTs) largely account for the scale-up of malaria diagnosis in endemic settings. However, diversity in labelling including the instructions for use (IFU) limits their interchangeability and user-friendliness. Uniform, easy to follow and consistent labelling, aligned with international standards and appropriate for the level of the end user’s education and training, is crucial but a consolidated resource of information regarding best practices for IFU and labelling of RDT devices, packaging and accessories is not available.
The Roll Back Malaria Partnership (RBM) commissioned the compilation of international standards and regulatory documents and published literature containing specifications and/or recommendations for RDT design, packaging and labelling of in vitro diagnostics (IVD) (which includes RDTs), complemented with a questionnaire based survey of RDT manufacturers and implementers. A summary of desirable RDT labelling characteristics was compiled, which was reviewed and discussed during a RBM Stakeholder consultation meeting and subsequently amended and refined by a dedicated task force consisting of country programme implementers, experts in RDT implementation, IVD regulatory experts and manufacturers.
This process led to the development of consensus documents with a list of suggested terms and abbreviations as well as specifications for labelling of box, device packaging, cassettes, buffer bottle and accessories (lancets, alcohol swabs, transfer devices, desiccants). Emphasis was placed on durability (permanent printing or water-resistant labels), legibility (font size, letter type), comprehension (use of symbols) and ease of reference (e.g. place of labelling on the box or cassette packaging allowing quick oversight). A generic IFU template was developed, comprising background information, a template for procedure and reading/interpretation, a selection of appropriate references and a symbol key of internationally recognized symbols together with suggestions about appropriate lay-out, style and readability.
The present document together with its additional files compiled proposes best practices in labelling and IFU for malaria RDTs. It is expected that compliance with these best practices will increase harmonization among the different malaria RDT products available on the market and improve their user-friendliness.
Electronic supplementary material
The online version of this article (doi:10.1186/1475-2875-13-505) contains supplementary material, which is available to authorized users.
PMCID: PMC4302121  PMID: 25519980
Malaria RDT; Harmonization; Best practices; Labeling; Instructions for use
2.  Change in Cognitive Functioning Following Acute Antidepressant Treatment in Late-Life Depression 
Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for geriatric depression. The association of late-life depression and cognitive impairment has been well documented. However, there have been few placebo-controlled trials examining the impact of SSRIs on cognitive functioning.
Pre-post neuropsychological data collected as part of an 8-week, double-blind, placebo-controlled trial of citalopram in depressed patients aged 75 years and older were used to examine change in cognitive functioning.
University affiliated outpatient psychiatry clinics.
One hundred seventy-four community dwelling men and women 75 years or older with non-psychotic unipolar depression.
Neuropsychological assessments included mental status (Mini-Mental Status Exam), psychomotor speed (WAIS-III Digit Symbol Subtest), reaction time (Choice Reaction Time), visual-spatial skill (Judgment of Line Orientation), executive functioning (Stroop Color/Word Test), and memory (Buschke Selective Reminding Test).
Differences in the pattern of change by treatment group depended on responder status. Citalopram non-responders were the only group to decline on verbal learning and psychomotor speed. Citalopram responders showed significant improvement in visuospatial functioning compared to non-responders in either condition, but their improvement was not greater than responders on placebo. Citalopram responders showed greater improvement on psychomotor speed than citalopram non-responders, but their improvement was not greater than placebo responders or non-responders.
Medication may have a deleterious effect on some aspects of cognition among patients age 75 and over who have not responded. This suggests that patients should not be maintained on a medication if they have not had an adequate response.
PMCID: PMC3852681  PMID: 19916207
cognitive functioning; cognitive impairment; geriatric depression; late-life depression; citalopram
3.  Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa 
PLoS Medicine  2013;10(9):e1001511.
Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial.
Please see later in the article for the Editors' Summary
Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
Methods and Findings
Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants—all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%–100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%–100%) by unannounced pill counts and 97.2% (90.6%–100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.
The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use.
Please see later in the article for the Editors' Summary
Editors' Summary
Every year, about 2.5 million people (mostly living in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an HIV-infected partner, destroys immune system cells, leaving infected individuals susceptible to other infections. There is no cure for AIDS, although antiretroviral drugs can hold HIV in check, and there is no vaccine against HIV infection. Individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few low risk sexual partners, and by always using a condom. In addition, antiretroviral drugs can potentially be used in two ways to reduce HIV transmission. First, these drugs could be given to HIV-positive individuals to reduce their infectiousness. Second, antiretroviral drugs could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—pre-exposure prophylaxis (PrEP)—has provided varying levels of protection against HIV infection in randomized controlled trials (RCT; studies that monitor the outcomes of groups of patients randomly assigned to receive different test drugs or a placebo/dummy drug).
Why Was This Study Done?
One hypothesis for the varying efficacy of PrEP in RCTs is differential adherence—differences in whether trial participants took the antiretroviral drugs correctly. Antiretroviral drugs only control HIV infections effectively when they are taken regularly and adherence to antiretroviral PrEP is probably also important for HIV prevention. Here, the researchers investigate adherence to antiretroviral prophylaxis in a substudy within the Partners PrEP Study, a placebo-controlled RCT of oral antiretroviral drugs among nearly 5,000 HIV-uninfected members of serodiscordant couples in East Africa. In serodiscordant couples, only one partner is HIV-positive; 20% of couples in Africa who know their HIV status are serodiscordant. In the Partner PrEP Study, the efficacy of HIV protection with oral antiretroviral drugs was 67%–75%.
What Did the Researchers Do and Find?
The researchers selected a “convenience” sample—a sample is taken non-randomly from a population that is close at hand—of 1,147 HIV-uninfected partners enrolled in Uganda. They used unannounced home-based pill counts (an approach that reduced the chance of participants dumping unused pills to appear more adherent than they actually were) and electronic pill bottle monitoring (a microchip in the medication bottle cap recorded whenever the bottle was opened) to measure PrEP adherence in this cohort. All the participants received adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell below 80%. Fourteen participants, all of whom had been assigned to placebo, became HIV-positive during the adherence substudy. The average adherence to PrEP was 99.1% and 97.2% as measured by unannounced pill counts and by electronic monitoring, respectively. About 7% and 26% of participants had less than 80% adherence as measured by unannounced pill count and electronic monitoring, respectively, during at least one 3-month period of the substudy. Greater than 80% adherence was associated with the first 6 months of PrEP use and polygamous marriage. Adherence less than 80% was associated with report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use. Finally, the adherence intervention (intensified counseling) was well received and in the first unannounced pill count after the intervention, adherence increased to above 80% in 92% of participants.
What Do These Findings Mean?
These findings indicate that the high level of PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high level of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. The findings also suggest that low PrEP adherence is associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Several aspects of the study design may limit the accuracy of these findings. For example, although the adherence measures used here are probably more accurate than participant reports of missed doses and clinic-based pill counts (adherence measures that are often used in RCTs), they are not perfect. Nevertheless, these findings provide further support for the ability of PrEP to prevent HIV acquisition when taken regularly; they suggest that adherence interventions in the implementation setting should address sexual behavior, risk perception, and heavy alcohol use; and they provide data to guide ethical decisions about resource allocation for prevention and treatment of HIV infection.
Additional Information
Please access these Web sites via the online version of this summary at
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on HIV transmission and prevention and on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Uganda, on HIV prevention, and on PrEP (in English and Spanish)
PrEP Watch provides detailed information about PrEP and links to other resources; it includes personal stories from people who have chosen to use PrEP
More information about the Partners PrEP Study is available
Personal stories about living with HIV/AIDS are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline
PMCID: PMC3769210  PMID: 24058300
4.  Symbolic and non symbolic numerical representation in adults with and without developmental dyscalculia 
The question whether Developmental Dyscalculia (DD; a deficit in the ability to process numerical information) is the result of deficiencies in the non symbolic numerical representation system (e.g., a group of dots) or in the symbolic numerical representation system (e.g., Arabic numerals) has been debated in scientific literature. It is accepted that the non symbolic system is divided into two different ranges, the subitizing range (i.e., quantities from 1-4) which is processed automatically and quickly, and the counting range (i.e., quantities larger than 4) which is an attention demanding procedure and is therefore processed serially and slowly. However, so far no study has tested the automaticity of symbolic and non symbolic representation in DD participants separately for the subitizing and the counting ranges.
DD and control participants undergo a novel version of the Stroop task, i.e., the Enumeration Stroop. They were presented with a random series of between one and nine written digits, and were asked to name either the relevant written digit (in the symbolic task) or the relevant quantity of digits (in the non symbolic task) while ignoring the irrelevant aspect.
DD participants, unlike the control group, didn't show any congruency effect in the subitizing range of the non symbolic task.
These findings suggest that DD may be impaired in the ability to process symbolic numerical information or in the ability to automatically associate the two systems (i.e., the symbolic vs. the non symbolic). Additionally DD have deficiencies in the non symbolic counting range.
PMCID: PMC3527185  PMID: 23190433
5.  Evaluation of Consumer Understanding of Different Front-of-Package Nutrition Labels, 2010–2011 
Governments throughout the world are using or considering various front-of-package (FOP) food labeling systems to provide nutrition information to consumers. Our web-based study tested consumer understanding of different FOP labeling systems.
Adult participants (N = 480) were randomized to 1 of 5 groups to evaluate FOP labels: 1) no label; 2) multiple traffic light (MTL); 3) MTL plus daily caloric requirement icon (MTL+caloric intake); 4) traffic light with specific nutrients to limit based on food category (TL+SNL); or 5) the Choices logo. Total percentage correct quiz scores were created reflecting participants’ ability to select the healthier of 2 foods and estimate amounts of saturated fat, sugar, and sodium in foods. Participants also rated products on taste, healthfulness, and how likely they were to purchase the product. Quiz scores and product perceptions were compared with 1-way analysis of variance followed by post-hoc Tukey tests.
The MTL+caloric intake group (mean [standard deviation], 73.3% [6.9%]) and Choices group (72.5% [13.2%]) significantly outperformed the no label group (67.8% [10.3%]) and the TL+SNL group (65.8% [7.3%]) in selecting the more healthful product on the healthier product quiz. The MTL and MTL+caloric intake groups achieved average scores of more than 90% on the saturated fat, sugar, and sodium quizzes, which were significantly better than the no label and Choices group average scores, which were between 34% and 47%.
An MTL+caloric intake label and the Choices symbol hold promise as FOP labeling systems and require further testing in different environments and population subgroups.
PMCID: PMC3475525  PMID: 22995103
6.  Distraction of Symbolic Behavior in Regular Classrooms 
The purpose of the present study is to develop more precise methods to explore the interaction between contextual factors in teacher instructions in regular classroom settings and students’ abilities to use symbolic information in the instruction. The ability to easily show symbolic behavior could be expected to influence student’s capacity to be active and participate. The present study examines distraction in students’ shifts from the use of “non-symbolic” to “symbolic” behavior in regular classroom settings. The 53 students (29 boys and 24 girls), ages 11–13 years old, who participated in the study were from three classes in the same Swedish compulsory regular school. Based on their test performances in a previous study, 25 students (47%) were defined as showing symbolic behavior (symbolic), and 28 students (53%) as not showing it (non-symbolic). In the present study, new test trials with distractors were added. Students from both the symbolic and non-symbolic groups scored significantly fewer correct answers on the post-training test trials with distraction stimuli (p < 0.05) than in post-training test trials without distraction. In the post-training test trials with competing arbitrary distractors, both groups were distracted significantly more than in the post-training test trials with competing non-arbitrary distractors (p < 0.05). The results indicate that a relatively easily administered and socially acceptable procedure seems to give observational data about variations in students’ symbolic behavior in relation to contextual factors in regular classroom. The main conclusion to be drawn from the results is that the observational procedure used in this study seems to have a potential to be used to explore the interaction between contextual factors and more complex student behavior such as cognition and the pragmatic use of language in regular classroom.
PMCID: PMC3505021  PMID: 23189068
symbolic behavior; stimulus equivalence; matching-to-sample; classroom setting; analog observation; inclusion
7.  Functional Imaging of Numerical Processing in Adults and 4-y-Old Children 
PLoS Biology  2006;4(5):e125.
Adult humans, infants, pre-school children, and non-human animals appear to share a system of approximate numerical processing for non-symbolic stimuli such as arrays of dots or sequences of tones. Behavioral studies of adult humans implicate a link between these non-symbolic numerical abilities and symbolic numerical processing (e.g., similar distance effects in accuracy and reaction-time for arrays of dots and Arabic numerals). However, neuroimaging studies have remained inconclusive on the neural basis of this link. The intraparietal sulcus (IPS) is known to respond selectively to symbolic numerical stimuli such as Arabic numerals. Recent studies, however, have arrived at conflicting conclusions regarding the role of the IPS in processing non-symbolic, numerosity arrays in adulthood, and very little is known about the brain basis of numerical processing early in development. Addressing the question of whether there is an early-developing neural basis for abstract numerical processing is essential for understanding the cognitive origins of our uniquely human capacity for math and science. Using functional magnetic resonance imaging (fMRI) at 4-Tesla and an event-related fMRI adaptation paradigm, we found that adults showed a greater IPS response to visual arrays that deviated from standard stimuli in their number of elements, than to stimuli that deviated in local element shape. These results support previous claims that there is a neurophysiological link between non-symbolic and symbolic numerical processing in adulthood. In parallel, we tested 4-y-old children with the same fMRI adaptation paradigm as adults to determine whether the neural locus of non-symbolic numerical activity in adults shows continuity in function over development. We found that the IPS responded to numerical deviants similarly in 4-y-old children and adults. To our knowledge, this is the first evidence that the neural locus of adult numerical cognition takes form early in development, prior to sophisticated symbolic numerical experience. More broadly, this is also, to our knowledge, the first cognitive fMRI study to test healthy children as young as 4 y, providing new insights into the neurophysiology of human cognitive development.
This functional imaging study provides evidence for a neurobiological link between early non-symbolic numerical abilities of 4 year-old children and the more symbolic numerical processing of adults.
PMCID: PMC1431577  PMID: 16594732
8.  Assessment of the knowledge of graphical symbols labelled on malaria rapid diagnostic tests in four international settings 
Malaria Journal  2011;10:331.
Graphical symbols on in vitro diagnostics (IVD symbols) replace the need for text in different languages and are used on malaria rapid diagnostic tests (RDTs) marketed worldwide. The present study assessed the comprehension of IVD symbols labelled on malaria RDT kits among laboratory staff in four different countries.
Participants (n = 293) in Belgium (n = 96), the Democratic Republic of the Congo (DRC, n = 87), Cambodia (n = 59) and Cuba (n = 51) were presented with an anonymous questionnaire with IVD symbols extracted from ISO 15223 and EN 980 presented as stand-alone symbols (n = 18) and in context (affixed on RDT packages, n = 16). Responses were open-ended and scored for correctness by local professionals.
Presented as stand-alone, three and five IVD symbols were correctly scored for comprehension by 67% and 50% of participants; when contextually presented, five and seven symbols reached the 67% and 50% correct score respectively. 'Batch code' scored best (correctly scored by 71.3% of participants when presented as stand-alone), 'Authorized representative in the European Community' scored worst (1.4% correct). Another six IVD symbols were scored correctly by less than 10% of participants: 'Do not reuse', 'In vitro diagnostic medical device', 'Sufficient for', 'Date of manufacture', 'Authorised representative in EC', and 'Do not use if package is damaged'. Participants in Belgium and Cuba both scored six symbols above the 67% criterion, participants from DRC and Cambodia scored only two and one symbols above this criterion. Low correct scores were observed for safety-related IVD symbols, such as for 'Biological Risk' (42.7%) and 'Do not reuse' (10.9%).
Comprehension of IVD symbols on RDTs among laboratory staff in four international settings was unsatisfactory. Administrative and outreach procedures should be undertaken to assure their acquaintance by end-users.
PMCID: PMC3215670  PMID: 22047089
Graphical symbols; in vitro diagnostics; ISO 15223; malaria rapid diagnostic tests
9.  Individual differences in non-symbolic numerical abilities predict mathematical achievements but contradict ATOM 
A significant debate surrounds the nature of the cognitive mechanisms involved in non-symbolic number estimation. Several studies have suggested the existence of the same cognitive system for estimation of time, space, and number, called “a theory of magnitude” (ATOM). In addition, researchers have proposed the theory that non-symbolic number abilities might support our mathematical skills. Despite the large number of studies carried out, no firm conclusions can be drawn on either topic.
In the present study, we correlated the performance of adults on non-symbolic magnitude estimations and symbolic numerical tasks. Non-symbolic magnitude abilities were assessed by asking participants to estimate which auditory tone lasted longer (time), which line was longer (space), and which group of dots was more numerous (number). To assess symbolic numerical abilities, participants were required to perform mental calculations and mathematical reasoning.
We found a positive correlation between non-symbolic and symbolic numerical abilities. On the other hand, no correlation was found among non-symbolic estimations of time, space, and number.
Our study supports the idea that mathematical abilities rely on rudimentary numerical skills that predate verbal language. By contrast, the lack of correlation among non-symbolic estimations of time, space, and number is incompatible with the idea that these magnitudes are entirely processed by the same cognitive system.
PMCID: PMC3711901  PMID: 23815866
Subitizing; ANS; OTS; Mathematical achievement; ATOM
10.  Beneficial effects of short-term combination exercise training on diverse cognitive functions in healthy older people: study protocol for a randomized controlled trial 
Trials  2012;13:200.
Results of previous studies have shown that exercise training can improve cognitive functions in healthy older people. Some studies have demonstrated that long-term combination exercise training can facilitate memory function improvement better than either aerobic or strength exercise training alone. Nevertheless, it remains unclear whether short-term combination exercise training can improve diverse cognitive functions in healthy older people or not. We investigate the effects of four weeks of short-term combination exercise training on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) of healthy older people.
A single-blinded intervention with two parallel groups (combination exercise training; waiting list control) is used. Testers are blind to the study hypothesis and the participants’ group membership. Through an advertisement in a local newspaper, 64 healthy older adults are recruited and then assigned randomly to a combination exercise training group or a waiting list control group. Participants in the combination exercise training group must participate in the short-term combination exercise training (aerobic and strength exercise training) three days per week during the four weeks (12 workouts in total). The waiting list group does not participate in the combination exercise training. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the Verbal Fluency Task, Logical Memory, First and Second Names, Digit Span Forward, Digit span backward, Japanese Reading Test, Digit Cancellation Task, Digit Symbol Coding, and Symbol Search. We assess these outcome measures before and after the intervention.
This report is the first of a study that investigates the beneficial effects of short-term combination exercise training on diverse cognitive functions of older people. Our study is expected to provide sufficient evidence of short-term combination exercise’s effectiveness.
Trial registration
This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (Number UMIN000007828).
PMCID: PMC3495024  PMID: 23107038
11.  The use of contextual cues to improve warning symbol comprehension: making the connection for older adults 
Ergonomics  2013;56(8):1264-1279.
This study teased apart the effects of comprehensibility and complexity on older adults' comprehension of warning symbols by manipulating the relevance of additional information in further refining the meaning of the symbol. Symbols were systematically altered such that increased visual complexity (in the form of contextual cues) resulted in increased comprehensibility. One hundred older adults, aged 50–71 years, were tested on their comprehension of these symbols before and after training. High comprehensibility–complexity symbols were found to be better understood than low- or medium-comprehensibility–complexity symbols and the effectiveness of the contextual cues varied as a function of training. Therefore, the nature of additional detail determines whether increased complexity is detrimental or beneficial to older adults' comprehension – if the additional details provide ‘cues to knowledge’, older adults' comprehension improves as a result of the increased complexity. However, some cues may require training in order to be effective.
Practitioner Summary: Research suggests that older adults have greater difficulty in understanding more complex symbols. However, we found that when the complexity of symbols was increased through the addition of contextual cues, older adults' comprehension actually improved. Contextual cues aid older adults in making the connection between the symbol and its referent.
PMCID: PMC3783898  PMID: 23767856
warnings; safety symbols; ageing; training
12.  Beneficial effects of reading aloud and solving simple arithmetic calculations (learning therapy) on a wide range of cognitive functions in the healthy elderly: study protocol for a randomized controlled trial 
Trials  2012;13:32.
Almost all cognitive functions decline with age. Results of previous studies have shown that cognitive training related to everyday life (reading aloud and solving simple arithmetic calculations), namely learning therapy, can improve two cognitive function (executive functions and processing speed) in elderly people. However, it remains unclear whether learning therapy engenders improvement of various cognitive functions or not. We investigate the impact of learning therapy on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) in healthy older adults.
We use a single-blinded intervention with two parallel groups (a learning therapy group and a waiting list control group). Testers are blind to the study hypothesis and the group membership of participants. Through an advertisement in local newspaper, 64 healthy older adults are recruited. They will be assigned randomly to a learning therapy group or a waiting list control group. In the learning therapy group, participants are required to perform two cognitive tasks for 6 months: reading Japanese aloud and solving simple calculations. The waiting list group does not participate in the intervention. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the following: verbal fluency task, logical memory, first and second names, digit span forward, digit span backward, Japanese reading test, digit cancellation task, digit symbol coding, and symbol search. We assess these outcome measures before and after the intervention.
This report is the first study which investigates the beneficial effects of learning therapy on a wide range of cognitive functions of elderly people. Our study provides sufficient evidence of learning therapy effectiveness. Most cognitive functions, which are correlated strongly with daily life activities, decrease with age. These study results can elucidate effects of cognitive training on elderly people.
Trial registration
This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (No. UMIN000006998).
PMCID: PMC3349518  PMID: 22483196
13.  Learning and processing of nonverbal symbolic information in bilinguals and monolinguals 
Frontiers in Psychology  2014;5:1147.
Bilinguals have been shown to outperform monolinguals on word learning and on inhibition tasks that require competition resolution. Yet the scope of such bilingual advantages remains underspecified. We compared bilinguals and monolinguals on nonverbal symbolic learning and on competition resolution while processing newly-learned material. Participants were trained on 12 tone-to-symbol mappings, combining timbre, pitch, and duration of tones. During subsequent processing, participants viewed a display with four symbols, and were instructed to identify the symbol that matched a simultaneously-presented tone. On competition trials, two symbols matched the tone in timbre and pitch, but only one matched the tone on timbre, pitch, and duration. No learning differences emerged between 27 Spanish-English bilinguals and 27 English monolinguals, and more successful learners performed better on the Peabody Picture Vocabulary task. During the processing task, competition trials yielded responses with lower accuracies and longer latencies than control trials. Further, in both groups, more successful learning of tone-to-symbol mappings was associated with more successful retrieval during processing. In monolinguals, English receptive vocabulary scores also influenced retrieval efficiency during processing, with English/Spanish vocabulary less related to the novel processing task in bilinguals. Finally, to examine inhibition of competing stimuli, priming probes were presented after each tone-symbol processing trial. These probes suggested that bilinguals, and to a lesser extent monolinguals, showed residual inhibition of competitors at 200 ms post-target identification. Together, findings suggest that learning of novel symbolic information may depend in part on previous linguistic knowledge (not bilingualism per se), and that, during processing of newly-learned material, subtle differences in retrieval and competition resolution may emerge between bilinguals and monolinguals.
PMCID: PMC4199272  PMID: 25360125
bilingualism; learning; nonlinguistic processing; priming; competition resolution; inhibition; auditory word identification; vocabulary
14.  Impact of a pharmacist-prepared interim residential care medication administration chart on gaps in continuity of medication management after discharge from hospital to residential care: a prospective pre- and post-intervention study (MedGap Study) 
BMJ Open  2012;2(3):e000918.
To test the impact of a hospital pharmacist-prepared interim residential care medication administration chart (IRCMAC) on medication administration errors and use of locum medical services after discharge from hospital to residential care.
Prospective pre-intervention and post-intervention study.
One major acute care hospital and one subacute aged-care hospital; 128 residential care facilities (RCF) in Victoria, Australia.
428 patients (median age 84 years, IQR 79–88) discharged to a RCF from an inpatient ward over two 12-week periods.
Seven-day IRCMAC auto-populated with patient and medication data from the hospitals' pharmacy dispensing software, completed and signed by a hospital pharmacist and sent with the patient to the RCF.
Primary and secondary outcome measures
Primary end points were the proportion of patients with one or more missed or significantly delayed (>50% of prescribed dose interval) medication doses, and the proportion of patients whose RCF medication chart was written by a locum doctor, in the 24 h after discharge. Secondary end points included RCF staff and general practitioners' opinions about the IRCMAC.
The number of patients who experienced one or more missed or delayed doses fell from 37/202 (18.3%) to 6/226 (2.7%) (difference in percentages 15.6%, 95% CI 9.5% to 21.9%, p<0.001). The number of patients whose RCF medication chart was written by a locum doctor fell from 66/202 (32.7%) to 25/226 (11.1%) (difference in percentages 21.6%, 95% CI 13.5% to 29.7%, p<0.001). For 189/226 (83.6%) discharges, RCF staff reported that the IRCMAC improved continuity of care; 31/35 (88.6%) general practitioners said that the IRCMAC reduced the urgency for them to attend the RCF and 35/35 (100%) said that IRCMACs should be provided for all patients discharged to a RCF.
A hospital pharmacist-prepared IRCMAC significantly reduced medication errors and use of locum medical services after discharge from hospital to residential care.
Article summary
Article focus
Medication administration errors are common when patients are discharged from hospital to a residential care facility (RCF). In Australia, a contributing factor is the need for the patient's primary care doctor to attend the RCF at short notice to write a medication administration chart; when the doctor cannot attend, doses may be missed or delayed and a locum doctor may be called to write a medication chart.
The objective of this study was to test the impact of a hospital pharmacist-prepared residential care medication administration chart (IRCMAC) on medication administration errors and use of locum medical services after discharge from hospital.
Key messages
Provision of a hospital pharmacist-prepared IRCMAC resulted in significant reductions in missed or delayed medication doses and use of locum medical services after discharge from hospital.
RCF staff reported that the IRCMAC improved continuity of care, and primary care doctors reported that it reduced pressure on them to attend RCFs at short notice.
Strengths and limitations of this study
This is the first study to evaluate the impact of a hospital-provided IRCMAC on medication errors or use of locum medical services. Strengths were that the two study groups were well matched in terms of demographics, ward type, number of medications and number of RCFs.
The main limitations were the use of a pre-intervention and post-intervention study design and data collection via RCF staff telephone interview. However, quantitative data on medication errors and use of locum services were validated by strongly positive feedback from RCF staff and doctors and widespread uptake and ongoing use of the IRCMAC.
PMCID: PMC3367148  PMID: 22637373
15.  Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints 
PLoS Medicine  2011;8(4):e1000431.
Aaron Kesselheim and colleagues analyzed unsealed whistleblower complaints against pharmaceutical companies filed in US federal fraud cases that contained allegations of off-label marketing, and develop a taxonomy of the various off-label practices.
Despite regulatory restrictions, off-label marketing of pharmaceutical products has been common in the US. However, the scope of off-label marketing remains poorly characterized. We developed a typology for the strategies and practices that constitute off-label marketing.
Methods and Findings
We obtained unsealed whistleblower complaints against pharmaceutical companies filed in US federal fraud cases that contained allegations of off-label marketing (January 1996–October 2010) and conducted structured reviews of them. We coded and analyzed the strategic goals of each off-label marketing scheme and the practices used to achieve those goals, as reported by the whistleblowers. We identified 41 complaints arising from 18 unique cases for our analytic sample (leading to US$7.9 billion in recoveries). The off-label marketing schemes described in the complaints had three non–mutually exclusive goals: expansions to unapproved diseases (35/41, 85%), unapproved disease subtypes (22/41, 54%), and unapproved drug doses (14/41, 34%). Manufacturers were alleged to have pursued these goals using four non–mutually exclusive types of marketing practices: prescriber-related (41/41, 100%), business-related (37/41, 90%), payer-related (23/41, 56%), and consumer-related (18/41, 44%). Prescriber-related practices, the centerpiece of company strategies, included self-serving presentations of the literature (31/41, 76%), free samples (8/41, 20%), direct financial incentives to physicians (35/41, 85%), and teaching (22/41, 54%) and research activities (8/41, 20%).
Off-label marketing practices appear to extend to many areas of the health care system. Unfortunately, the most common alleged off-label marketing practices also appear to be the most difficult to control through external regulatory approaches.
Please see later in the article for the Editors' Summary
Editors' Summary
Before a pharmaceutical company can market a new prescription drug in the US, the drug has to go through a long approval process. After extensive studies in the laboratory and in animals, the pharmaceutical company must test the drug's safety and efficacy in a series of clinical trials in which groups of patients with specific diseases are given the drug according to strict protocols. The results of these trials are reviewed by Federal Drug Administration (FDA, the body that regulates drugs in the US) and, when the FDA is satisfied that the drug is safe and effective for the conditions in which it is tested, it approves the drug for sale. An important part of the approval process is the creation of the “drug label,” a detailed report that specifies the exact diseases and patient groups in which the drug can be used and the approved doses of the drug.
Why Was This Study Done?
Physicians can, however, legally use FDA-approved drugs “off-label.” That is, they can prescribe drugs for a different disease, in a different group of patients, or at a different dose to that specified in the drug's label. However, because drugs' manufacturers stand to benefit financially from off-label use through increased drugs sales, the FDA prohibits them from directly promoting unapproved uses. The fear is that such marketing would encourage the widespread use of drugs in settings where their efficacy and safety has not been rigorously tested, exposing patients to uncertain benefits and possible adverse effects. Despite the regulatory restrictions, off-label marketing seems to be common. In 2010, for example, at least six pharmaceutical companies settled US government investigations into alleged off-label marketing programs. Unfortunately, the tactics used by pharmaceutical companies for off-label marketing have been poorly understood in the medical community, in part because pharmaceutical industry insiders (“whistleblowers”) are the only ones who can present in-depth knowledge of these tactics. In recent years, as more whistleblowers have come forward to allege off-label marketing, developing a more complete picture of the practice is now possible. In this study, the researchers attempt to systematically classify the strategies and practices used in off-labeling marketing by examining complaints filed by whistleblowers in federal enforcement actions where off-label marketing by pharmaceutical companies has been alleged.
What Did the Researchers Do and Find?
In their analysis of 41 whistleblower complaints relating to 18 alleged cases of off-label marketing in federal fraud cases unsealed between January 1996 and October 2010, the researchers identified three non–mutually exclusive goals of off-label marketing schemes. The commonest goal (85% of cases) was expansion of drug use to unapproved diseases (for example, gabapentin, which is approved for the treatment of specific types of epilepsy, was allegedly promoted as a therapy for patients with psychiatric diseases such as depression). The other goals were expansion to unapproved disease subtypes (for example, some antidepressant drugs approved for adults were allegedly promoted to pediatricians for use in children) and expansion to unapproved drug dosing strategies, typically higher doses. The researchers also identified four non–mutually exclusive types of marketing practices designed to achieve these goals. All of the whistleblowers alleged prescriber-related practices (including providing financial incentives and free samples to physicians), and most alleged internal practices intended to bolster off-label marketing, such as sales quotas that could only be met if the manufacturer's sales representatives promoted off-label drug use. Payer-related practices (for example, discussions with prescribers about ways to ensure insurance reimbursement for off-label prescriptions) and consumer-related practices (most commonly, the review of confidential patient charts to identify consumers who could be off-label users) were also alleged.
What Do These Findings Mean?
These findings suggest that off-labeling marketing practices extend to many parts of the health care delivery system. Because these practices were alleged by whistleblowers and were not the subject of testimony in a full trial, some of the practices identified by the researchers were not confirmed. Conversely, because most of the whistleblowers were US-based sales representatives, there may be other goals and strategies that this study has not identified. Nevertheless, these findings provide a useful snapshot of off-label marketing strategies and practices allegedly employed in the US over the past 15 years, which can now be used to develop new regulatory strategies aimed at effective oversight of off-label marketing. Importantly, however, these findings suggest that no regulatory strategy will be complete and effective unless physicians themselves fully understand the range of off-label marketing practices and their consequences for public health and act as a bulwark against continued efforts to engage in off-label promotion.
Additional Information
Please access these Web sites via the online version of this summary at
The US Food and Drug Administration provides detailed information about drug approval in the US for consumers and for health professionals; its Bad Ad Program aims to educate health care providers about the role they can play in ensuring that prescription drug advertising and promotion is truthful and not misleading.
The American Cancer Society has a page about off-label drug use
Wikipedia has pages on prescription drugs, on pharmaceutical marketing, and on off-label drug use (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Taxpayers Against Fraud is a nonprofit organization dedicated to helping whistleblowers, and it presents up-to-date information about False Claims Act cases
The Government Accountability Project is a nonprofit organization that seeks to promote corporate and government accountability by protecting whistleblowers, advancing occupational free speech, and empowering citizen activists
Healthy Skepticism is an international nonprofit membership association that aims to improve health by reducing harm from misleading health information
PMCID: PMC3071370  PMID: 21483716
16.  Effects of Two Commercial Electronic Prescribing Systems on Prescribing Error Rates in Hospital In-Patients: A Before and After Study 
PLoS Medicine  2012;9(1):e1001164.
In a before-and-after study, Johanna Westbrook and colleagues evaluate the change in prescribing error rates after the introduction of two commercial electronic prescribing systems in two Australian hospitals.
Considerable investments are being made in commercial electronic prescribing systems (e-prescribing) in many countries. Few studies have measured or evaluated their effectiveness at reducing prescribing error rates, and interactions between system design and errors are not well understood, despite increasing concerns regarding new errors associated with system use. This study evaluated the effectiveness of two commercial e-prescribing systems in reducing prescribing error rates and their propensities for introducing new types of error.
Methods and Results
We conducted a before and after study involving medication chart audit of 3,291 admissions (1,923 at baseline and 1,368 post e-prescribing system) at two Australian teaching hospitals. In Hospital A, the Cerner Millennium e-prescribing system was implemented on one ward, and three wards, which did not receive the e-prescribing system, acted as controls. In Hospital B, the iSoft MedChart system was implemented on two wards and we compared before and after error rates. Procedural (e.g., unclear and incomplete prescribing orders) and clinical (e.g., wrong dose, wrong drug) errors were identified. Prescribing error rates per admission and per 100 patient days; rates of serious errors (5-point severity scale, those ≥3 were categorised as serious) by hospital and study period; and rates and categories of postintervention “system-related” errors (where system functionality or design contributed to the error) were calculated. Use of an e-prescribing system was associated with a statistically significant reduction in error rates in all three intervention wards (respectively reductions of 66.1% [95% CI 53.9%–78.3%]; 57.5% [33.8%–81.2%]; and 60.5% [48.5%–72.4%]). The use of the system resulted in a decline in errors at Hospital A from 6.25 per admission (95% CI 5.23–7.28) to 2.12 (95% CI 1.71–2.54; p<0.0001) and at Hospital B from 3.62 (95% CI 3.30–3.93) to 1.46 (95% CI 1.20–1.73; p<0.0001). This decrease was driven by a large reduction in unclear, illegal, and incomplete orders. The Hospital A control wards experienced no significant change (respectively −12.8% [95% CI −41.1% to 15.5%]; −11.3% [−40.1% to 17.5%]; −20.1% [−52.2% to 12.4%]). There was limited change in clinical error rates, but serious errors decreased by 44% (0.25 per admission to 0.14; p = 0.0002) across the intervention wards compared to the control wards (17% reduction; 0.30–0.25; p = 0.40). Both hospitals experienced system-related errors (0.73 and 0.51 per admission), which accounted for 35% of postsystem errors in the intervention wards; each system was associated with different types of system-related errors.
Implementation of these commercial e-prescribing systems resulted in statistically significant reductions in prescribing error rates. Reductions in clinical errors were limited in the absence of substantial decision support, but a statistically significant decline in serious errors was observed. System-related errors require close attention as they are frequent, but are potentially remediable by system redesign and user training. Limitations included a lack of control wards at Hospital B and an inability to randomize wards to the intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Medication errors—for example, prescribing the wrong drug or giving a drug by the wrong route—frequently occur in health care settings and are responsible for thousands of deaths every year. Until recently, medicines were prescribed and dispensed using systems based on hand-written scripts. In hospitals, for example, physicians wrote orders for medications directly onto a medication chart, which was then used by the nursing staff to give drugs to their patients. However, drugs are now increasingly being prescribed using electronic prescribing (e-prescribing) systems. With these systems, prescribers use a computer and order medications for their patients with the help of a drug information database and menu items, free text boxes, and prewritten orders for specific conditions (so-called passive decision support). The system reviews the patient's medication and known allergy list and alerts the physician to any potential problems, including drug interactions (active decision support). Then after the physician has responded to these alerts, the order is transmitted electronically to the pharmacy and/or the nursing staff who administer the prescription.
Why Was This Study Done?
By avoiding the need for physicians to write out prescriptions and by providing active and passive decision support, e-prescribing has the potential to reduce medication errors. But, even though many countries are investing in expensive commercial e-prescribing systems, few studies have evaluated the effects of these systems on prescribing error rates. Moreover, little is known about the interactions between system design and errors despite fears that e-prescribing might introduce new errors. In this study, the researchers analyze prescribing error rates in hospital in-patients before and after the implementation of two commercial e-prescribing systems.
What Did the Researchers Do and Find?
The researchers examined medication charts for procedural errors (unclear, incomplete, or illegal orders) and for clinical errors (for example, wrong drug or dose) at two Australian hospitals before and after the introduction of commercial e-prescribing systems. At Hospital A, the Cerner Millennium e-prescribing system was introduced on one ward; three other wards acted as controls. At Hospital B, the researchers compared the error rates on two wards before and after the introduction of the iSoft MedChart e-prescribing system. The introduction of an e-prescribing system was associated with a substantial reduction in error rates in the three intervention wards; error rates on the control wards did not change significantly during the study. At Hospital A, medication errors declined from 6.25 to 2.12 per admission after the introduction of e-prescribing whereas at Hospital B, they declined from 3.62 to 1.46 per admission. This reduction in error rates was mainly driven by a reduction in procedural error rates and there was only a limited change in overall clinical error rates. Notably, however, the rate of serious errors decreased across the intervention wards from 0.25 to 0.14 per admission (a 44% reduction), whereas the serious error rate only decreased by 17% in the control wards during the study. Finally, system-related errors (for example, selection of an inappropriate drug located on a drop-down menu next to a likely drug selection) accounted for 35% of errors in the intervention wards after the implementation of e-prescribing.
What Do These Findings Mean?
These findings show that the implementation of these two e-prescribing systems markedly reduced hospital in-patient prescribing error rates, mainly by reducing the number of incomplete, illegal, or unclear medication orders. The limited decision support built into both the e-prescribing systems used here may explain the limited reduction in clinical error rates but, importantly, both e-prescribing systems reduced serious medication errors. Finally, the high rate of system-related errors recorded in this study is worrying but is potentially remediable by system redesign and user training. Because this was a “real-world” study, it was not possible to choose the intervention wards randomly. Moreover, there was no control ward at Hospital B, and the wards included in the study had very different specialties. These and other aspects of the study design may limit the generalizability of these findings, which need to be confirmed and extended in additional studies. Even so, these findings provide persuasive evidence of the current and potential ability of commercial e-prescribing systems to reduce prescribing errors in hospital in-patients provided these systems are continually monitored and refined to improve their performance.
Additional Information
Please access these Web sites via the online version of this summary at
ClinfoWiki has pages on medication errors and on electronic prescribing (note: the Clinical Informatics Wiki is a free online resource that anyone can add to or edit)
Electronic prescribing in hospitals challenges and lessons learned describes the implementation of e-prescribing in UK hospitals; more information about e-prescribing in the UK is available on the NHS Connecting for Health Website
The Clinicians Guide to e-Prescribing provides up-to-date information about e-prescribing in the USA
Information about e-prescribing in Australia is also available
Information about electronic health records in Australia
PMCID: PMC3269428  PMID: 22303286
17.  Association of Medical Students' Reports of Interactions with the Pharmaceutical and Medical Device Industries and Medical School Policies and Characteristics: A Cross-Sectional Study 
PLoS Medicine  2014;11(10):e1001743.
Aaron Kesselheim and colleagues compared US medical students' survey responses regarding pharmaceutical company interactions with the schools' AMSA PharmFree scorecard and Institute on Medicine as a Profession's (IMAP) scores.
Please see later in the article for the Editors' Summary
Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors.
Methods and Findings
Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA) PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty–industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH) funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50–2.00] versus 1.77 [1.50–2.18], adjusted to compare scores on the same scale). Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11–0.44; marketing representative access policies, r = 0.51, 95% CI 0.36–0.63). Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19–0.72; IMAP score, OR 0.45, 95% CI 0.19–1.04) and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15–0.69; IMAP score, OR 0.37, 95% CI 0.14–0.95) than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly versus privately funded school did not alter the association. Policies limiting gifts, meals, and speaking bureaus were associated with students reporting having not received gifts and having not interacted with marketing representatives. Policy dimensions reflecting the regulation of industry involvement in educational activities (e.g., continuing medical education, travel compensation, and scholarships) were associated with perceived separation between faculty and industry. The study is limited by potential for recall bias and the cross-sectional nature of the survey, as school curricula and industry interaction policies may have changed since the time of the survey administration and study analysis.
As medical schools review policies regulating medical students' industry interactions, limitations on receipt of gifts and meals and participation of faculty in speaking bureaus should be emphasized, and policy makers should pay greater attention to less research-intensive institutions.
Please see later in the article for the Editors' Summary
Editors' Summary
Making and selling prescription drugs and medical devices is big business. To promote their products, pharmaceutical and medical device companies build relationships with physicians by providing information on new drugs, by organizing educational meetings and sponsored events, and by giving gifts. Financial relationships begin early in physicians' careers, with companies providing textbooks and other gifts to first-year medical students. In medical school settings, manufacturers may help to inform trainees and physicians about developments in health care, but they also create the potential for harm to patients and health care systems. These interactions may, for example, reduce trainees' and trained physicians' skepticism about potentially misleading promotional claims and may encourage physicians to prescribe new medications, which are often more expensive than similar unbranded (generic) drugs and more likely to be recalled for safety reasons than older drugs. To address these and other concerns about the potential career-long effects of interactions between medical trainees and industry, many teaching hospitals and medical schools have introduced policies to limit such interactions. The development of these policies has been supported by expert professional groups and medical societies, some of which have created scales to evaluate the strength of the implemented industry interaction policies.
Why Was This Study Done?
The impact of policies designed to limit interactions between students and industry on student behavior is unclear, and it is not known which aspects of the policies are most predictive of student behavior. This information is needed to ensure that the policies are working and to identify ways to improve them. Here, the researchers investigate which medical school characteristics and which aspects of industry interaction policies are most predictive of students' reported behaviors and beliefs by comparing information collected in a national survey of US medical students with the strength of their schools' industry interaction policies measured on two scales—the American Medical Student Association (AMSA) PharmFree Scorecard and the Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database.
What Did the Researchers Do and Find?
The researchers compared information about reported gift acceptance, interactions with marketing representatives, and the perceived adequacy of faculty–industry separation collected from 1,610 medical students at 121 US medical schools with AMSA and IMAP scores for the schools evaluated a year earlier. Students at schools with the highest ranked interaction policies based on the AMSA score were 63% less likely to accept gifts as students at the lowest ranked schools. Students at the highest ranked schools based on the IMAP score were about half as likely to accept gifts as students at the lowest ranked schools, although this finding was not statistically significant (it could be a chance finding). Similarly, students at the highest ranked schools were 70% less likely to interact with sales representatives as students at the lowest ranked schools. These associations became statistically nonsignificant after controlling for the amount of research funding each school received from the US National Institutes of Health (NIH). Policies limiting gifts, meals, and being a part of speaking bureaus (where companies pay speakers to present information about the drugs for dinners and other events) were associated with students' reports of receiving no gifts and of non-interaction with sales representatives. Finally, policies regulating industry involvement in educational activities were associated with the perceived separation between faculty and industry, which was regarded as adequate by most of the students at schools with such policies.
What Do These Findings Mean?
These findings suggest that policies designed to limit industry interactions with medical students need to address multiple aspects of these interactions to achieve changes in the behavior and attitudes of trainees, but that policies limiting gifts, meals, and speaking bureaus may be particularly important. These findings also suggest that the level of NIH funding plays an important role in students' self-reported behaviors and their perceptions of industry, possibly because institutions with greater NIH funding have the resources needed to implement effective policies. The accuracy of these findings may be limited by recall bias (students may have reported their experiences inaccurately), and by the possibility that industry interaction policies may have changed in the year that elapsed between policy grading and the student survey. Nevertheless, these findings suggest that limitations on gifts should be emphasized when academic medical centers refine their policies on interactions between medical students and industry and that particular attention should be paid to the design and implementation of policies that regulate industry interactions in institutions with lower levels of NIH funding.
Additional Information
Please access these websites via the online version of this summary at
The UK General Medical Council provides guidance on financial and commercial arrangements and conflicts of interest as part of its good medical practice document, which describes what is required of all registered doctors in the UK
Information about the American Medical Student Association (AMSA) Just Medicine campaign (formerly the PharmFree campaign) and about the AMSA Scorecard is available
Information about the Institute on Medicine as a Profession (IMAP) and about its Conflicts of Interest Policy Database is also available
“Understanding and Responding to Pharmaceutical Promotion: A Practical Guide” is a manual prepared by Health Action International and the World Health Organization that medical schools can use to train students how to recognize and respond to pharmaceutical promotion
The US Institute of Medicine's report “Conflict of Interest in Medical Research, Education, and Practice” recommends steps to identify, limit, and manage conflicts of interest
The ALOSA Foundation provides evidence-based, non-industry-funded education about treating common conditions and using prescription drugs
PMCID: PMC4196737  PMID: 25314155
18.  Estimation abilities of large numerosities in Kindergartners 
The approximate number system (ANS) is thought to be a building block for the elaboration of formal mathematics. However, little is known about how this core system develops and if it can be influenced by external factors at a young age (before the child enters formal numeracy education). The purpose of this study was to examine numerical magnitude representations of 5–6 year old children at 2 different moments of Kindergarten considering children's early number competence as well as schools' socio-economic index (SEI). This study investigated estimation abilities of large numerosities using symbolic and non-symbolic output formats (8–64). In addition, we assessed symbolic and non-symbolic early number competence (1–12) at the end of the 2nd (N = 42) and the 3rd (N = 32) Kindergarten grade. By letting children freely produce estimates we observed surprising estimation abilities at a very young age (from 5 year on) extending far beyond children's symbolic explicit knowledge. Moreover, the time of testing has an impact on the ANS accuracy since 3rd Kindergarteners were more precise in both estimation tasks. Additionally, children who presented better exact symbolic knowledge were also those with the most refined ANS. However, this was true only for 3rd Kindergarteners who were a few months from receiving math instructions. In a similar vein, higher SEI positively impacted only the oldest children's estimation abilities whereas it played a role for exact early number competences already in 2nd and 3rd graders. Our results support the view that approximate numerical representations are linked to exact number competence in young children before the start of formal math education and might thus serve as building blocks for mathematical knowledge. Since this core number system was also sensitive to external components such as the SEI this implies that it can most probably be targeted and refined through specific educational strategies from preschool on.
PMCID: PMC3756289  PMID: 24009591
approximate number system; early number competence; numeracy; estimation; non-symbolic numbers; symbolic numbers; socio-economic factors; mathematical development
19.  Preserved Learning during the Symbol–Digit Substitution Test in Patients with Schizophrenia, Age-Matched Controls, and Elderly 
Objective: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit–symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol–digit relationships are learned, two factors that may be impaired in schizophrenia. This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals.
Methods: Patients with schizophrenia (N = 30) were compared with age-matched healthy controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol–Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol–digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning.
Results: The repetition of the same symbol–digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing.
Conclusion: The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the interpretation of task scores for processing speed. Equal learning rates among the three groups suggest that unintentional learning in schizophrenia and in the elderly is preserved. These findings are important for the design of rehabilitation programs for schizophrenia.
PMCID: PMC4285106  PMID: 25610403
symbol–digit substitution test; coding task; processing speed; implicit learning; schizophrenia
20.  A study on the consumer's perception of front-of-pack nutrition labeling 
Nutrition Research and Practice  2009;3(4):300-306.
The goal of this research is to investigate the present situation for front of pack labeling in Korea and the perception of consumers for the new system of labeling, front of pack labeling, based on the consumer survey. We investigated the number of processed foods with front of pack labeling in one retailer in Youngin-si. And we also surveyed 1,019 participants nationwide whose ages were from 20 to 49; the knowledge of nutrition labeling, the knowledge of 'front of pack labeling', and the opinion about the labeling system. The data were analyzed using SAS statistics program. The results were as follows: 13.4% of processed foods had front of pack labeling, and 16.8% of the consumers always checked the nutrition labeling, while 32.7% of the consumers seldom checked it. In addition, 44.3% of the consumers think that 'front of pack labeling' is necessary, and 58.3% of the consumers think it is important to show the percentage of daily value as a way of 'front of pack labeling'. However, 32% of the consumer think the possibility of 'front of pack labeling' is slim. Meanwhile, 58.3% of the consumers think that it is important to have the color difference according to contents. The number of favorite nutrients in the front of pack was four or five. It seems that the recognition of current nutrition labeling has the influence on the willingness of using the future 'front of pack labeling'. Along with our study, the policy for 'front of pack labeling' has to be updated and improved constantly since 'front of pack labeling' helps consumer understand nutrition facts.
PMCID: PMC2809237  PMID: 20098583
Nutrition labeling; front-of-pack (FOP) nutrition labeling; back-of pack; consumer perception; survey
21.  Electrophysiological evidence for notation independence in numerical processing 
A dominant view in numerical cognition is that numerical comparisons operate on a notation independent representation (Dehaene, 1992). Although previous human neurophysiological studies using scalp-recorded event-related potentials (ERPs) on the numerical distance effect have been interpreted as supporting this idea, differences in the electrophysiological correlates of the numerical distance effect in symbolic notations (e.g. Arabic numerals) and non-symbolic notations (e.g. a set of visually presented dots of a certain number) are not entirely consistent with this view.
Methods and results
Two experiments were conducted to resolve these discrepancies. In Experiment 1, participants performed a symbolic and a non-symbolic numerical comparison task ("smaller or larger than 5?") with numerical values 1–4 and 6–9 while ERPs were recorded. Consistent with a previous report (Temple & Posner, 1998), in the symbolic condition the amplitude of the P2p ERP component (210–250 ms post-stimulus) was larger for values near to the standard than for values far from the standard whereas this pattern was reversed in the non-symbolic condition. However, closer analysis indicated that the reversal in polarity was likely due to the presence of a confounding stimulus effect on the early sensory ERP components for small versus larger numerical values in the non-symbolic condition. In Experiment 2 exclusively large numerosities (8–30) were used, thereby rendering sensory differences negligible, and with this control in place the numerical distance effect in the non-symbolic condition mirrored the symbolic condition of Experiment 1.
Collectively, the results support the claim of an abstract semantic processing stage for numerical comparisons that is independent of input notation.
PMCID: PMC1781950  PMID: 17214890
22.  Results of the Medications At Transitions and Clinical Handoffs (MATCH) Study: An Analysis of Medication Reconciliation Errors and Risk Factors at Hospital Admission 
This study was designed to determine risk factors and potential harm associated with medication errors at hospital admission.
Study pharmacist and hospital-physician medication histories were compared with medication orders to identify unexplained history and order discrepancies in 651 adult medicine service inpatients with 5,701 prescription medications. Discrepancies resulting in order changes were considered errors. Logistic regression was used to analyze the association of patient demographic and clinical characteristics including patients’ number of pre-admission prescription medications, pharmacies, prescribing physicians and medication changes; and presentation of medication bottles or lists. These factors were tested after controlling for patient demographics, admitting service and severity of illness.
Over one-third of study patients (35.9%) experienced 309 order errors; 85% of patients had errors originate in medication histories, and almost half were omissions. Cardiovascular agents were commonly in error (29.1%). If undetected, 52.4% of order errors were rated as potentially requiring increased monitoring or intervention to preclude harm; 11.7% were rated as potentially harmful. In logistic regression analysis, patient’s age ≥65 [odds ratio (OR), 2.17; 95% confidence interval (CI), 1.09–4.30] and number of prescription medications (OR, 1.21; 95% CI, 1.14–1.29) were significantly associated with errors potentially requiring monitoring or causing harm. Presenting a medication list (OR, 0.35; 95% CI, 0.19–0.63) or bottles (OR, 0.55; 95% CI, 0.27–1.10) at admission was beneficial.
Over one-third of the patients in our study had a medication error at admission, and of these patients, 85% had errors originate in their medication histories. Attempts to improve the accuracy of medication histories should focus on older patients with a large number of medications. Primary care physicians and other clinicians should help patients utilize and maintain complete, accurate and understandable medication lists.
PMCID: PMC2855002  PMID: 20180158
medication reconciliation; medication errors; medication history taking
23.  The effect of illustrations on patient comprehension of medication instruction labels 
BMC Family Practice  2005;6:26.
Labels with special instructions regarding how a prescription medication should be taken or its possible side effects are often applied to pill bottles. The goal of this study was to determine whether the addition of illustrations to these labels affects patient comprehension.
Study participants (N = 130) were enrolled by approaching patients at three family practice clinics in Toronto, Canada. Participants were asked to interpret two sets of medication instruction labels, the first with text only and the second with the same text accompanied by illustrations. Two investigators coded participants' responses as incorrect, partially correct, or completely correct. Health literacy levels of participants were measured using a validated instrument, the REALM test.
All participants gave a completely correct interpretation for three out of five instruction labels, regardless of whether illustrations were present or not. For the two most complex labels, only 34–55% of interpretations of the text-only version were completely correct. The addition of illustrations was associated with improved performance in 5–7% of subjects and worsened performance in 7–9% of subjects.
The commonly-used illustrations on the medication labels used in this study were of little or no use in improving patients' comprehension of the accompanying written instructions.
PMCID: PMC1177941  PMID: 15960849
24.  Effect of electronic prescribing with formulary decision support on medication tier, copayments, and adherence 
Medication non-adherence is prevalent. We assessed the effect of electronic prescribing (e-prescribing) with formulary decision support on preferred formulary tier usage, copayment, and concomitant adherence.
We retrospectively analyzed 14,682 initial pharmaceutical claims for angiotensin receptor blocker and inhaled steroid medications among 14,410 patients of 2189 primary care physicians (PCPs) who were offered e-prescribing with formulary decision support, including 297 PCPs who adopted it. Formulary decision support was initially non-interruptive, such that formulary tier symbols were displayed adjacent to medication names. Subsequently, interruptive formulary decision support alerts also interrupted e-prescribing when preferred-tier alternatives were available. A difference in differences design was used to compare the pre-post differences in medication tier for each new prescription attributed to non-adopters, low user (<30% usage rate), and high user PCPs (>30% usage rate). Second, we modeled the effect of formulary tier on prescription copayment. Last, we modeled the effect of copayment on adherence (proportion of days covered) to each new medication.
Compared with non-adopters, high users of e-prescribing were more likely to prescribe preferred-tier medications (vs. non-preferred tier) when both non-interruptive and interruptive formulary decision support were in place (OR 1.9 [95% CI 1.0-3.4], p = 0.04), but no more likely to prescribe preferred-tier when only non-interruptive formulary decision support was in place (p = 0.90). Preferred-tier claims had only slightly lower mean monthly copayments than non-preferred tier claims (angiotensin receptor blocker: $10.60 versus $11.81, inhaled steroid: $14.86 versus $16.42, p < 0.0001). Medication possession ratio was 8% lower for each $1.00 increase in monthly copayment to the one quarter power (p < 0.0001). However, we detected no significant direct association between formulary decision support usage and adherence.
Interruptive formulary decision support shifted prescribing toward preferred tiers, but these medications were only minimally less expensive in the studied patient population. In this context, formulary decision support did not significantly increase adherence. To impact cost-related non-adherence, formulary decision support will likely need to be paired with complementary drug benefit design. Formulary decision support should be studied further, with particular attention to its effect on adherence in the setting of different benefit designs.
PMCID: PMC4236533  PMID: 25167807
Clinical decision support; Electronic prescribing; Medication adherence
25.  Perceptions of prescription warning labels within an underserved population 
Pharmacy Practice  2014;12(1):387.
To understand how underserved populations attend to prescription warning label (PWL) instructions, examine the importance of PWL instructions to participants and describe the challenges associated with interpreting the information on PWLs.
Adults from an underserved population (racial and ethnic minorities, individuals with low income, older adults) who had a history of prescription medication use and were able to understand English took part in semi-structured interviews. Participants were presented with eight different prescription bottles with an attached PWL. Participants were asked, “If this prescription was yours, what information would you need to know about the medicine?” The number of participants who attended to the warning labels was noted. Other questions assessed the importance of PWLs, the challenges with understanding PWLs, and ways a pharmacist could help participant understanding of the PWL.
There were 103 participants. The mean age was 50.25 years (SD=18.05). Majority attended to the PWL. Participants not currently taking medications and who had limited health literacy were likely to overlook the warning labels. Majority rated the warning instructions to be extremely important (n=86, 83.5 %), wanted the pharmacist to help them understand PWLs by counseling them on the information on the label (n=63, 61.2%), and thought the graphics made the label information easy to understand.
PWLs are an important method of communicating medication information, as long as they are easily comprehensible to patients. In addition to placing PWLs on prescription bottles, health care providers need to counsel underserved populations on medication warnings, especially individuals with limited health literacy who are not currently using a prescription medication.
PMCID: PMC3955868  PMID: 24644523
Drug Labeling; Patient Education as Topic; Patient Safety; Vulnerable Populations; Health Literacy; United States

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