Does providing the correct diagnosis as feedback after self-explanation improve medical students diagnostic performance?

BACKGROUND: Self-explanation without feedback has been shown to improve medical students' diagnostic reasoning. While feedback is generally seen as beneficial for learning, available evidence of the value of its combination with self-explanation is conflicting. This study investigated the effect on medical students' diagnostic performance of adding immediate or delayed content-feedback to self-explanation while solving cases. METHODS: Ninety-four 3rd-year students from a Canadian medical school were randomly assigned to three experimental conditions (immediate-feedback, delayed-feedback, control). In the learning phase, all students solved four clinical cases by giving i) the most likely diagnosis, ii) two main arguments supporting this diagnosis, and iii) two plausible alternative diagnoses, while using self-explanation. The immediate-feedback group was given the correct diagnosis after each case; delayed-feedback group received the correct diagnoses only after the four cases; control group received no feedback. One week later, all students solved four near-transfer (i.e., same final diagnosis as the learning cases but different scenarios) and four far-transfer cases (i.e., different final diagnosis from the learning cases and different scenarios) by answering the same three questions. Students' diagnostic accuracy (score for the response to the first question only) and diagnostic performance (combined score of responses to the three questions) scores were assessed in each phase. Four one-way ANOVAs were performed on each of the two scores for near and far-transfer cases. RESULTS: There was a significant effect of experimental condition on diagnostic accuracy on near-transfer cases (p < .05). The immediate-feedback and delayed-feedback groups performed equally well, both better than control (respectively, mean = 90.73, standard deviation =10.69; mean = 89.92, standard deviation = 13.85; mean = 82.03, standard deviation = 17.66). The experimental conditions did not significantly differ on far-transfer cases. CONCLUSIONS: Providing feedback to students in the form of the correct diagnosis after using self-explanation with clinical cases is potentially beneficial to improve their diagnostic accuracy but this effect is limited to similar cases. Further studies should explore how more elaborated feedback combined with self-explanation may impact students' diagnostic performance on different cases.

Neurophysiological evidence of preserved connectivity in tuber tissue.

We present a case of preserved corticospinal connectivity in a cortical tuber, in a 10 year-old boy with intractable epilepsy and tuberous sclerosis complex (TSC). The patient had multiple subcortical tubers, one of which was located in the right central sulcus. In preparation for epilepsy surgery, motor mapping, by neuronavigated transcranial magnetic stimulation (nTMS) coupled with surface electromyography (EMG) was performed to locate the primary motor cortical areas. The resulting functional motor map revealed expected corticospinal connectivity in the left precentral gyrus. Surprisingly, robust contralateral deltoid and tibialis anterior motor evoked potentials (MEPs) were also elicited with direct stimulation of the cortical tuber in the right central sulcus. MRI with diffusion tensor imaging (DTI) tractography confirmed corticospinal fibers originating in the tuber. As there are no current reports of preserved connectivity between a cortical tuber and the corticospinal tract, this case serves to highlight the functional interdigitation of tuber and eloquent cortex. Our case also illustrates the widening spectrum of neuropathological abnormality in TSC that is becoming apparent with modern MRI methodology. Finally, our finding underscores the need for further study of preserved function in tuber tissue during presurgical workup in patients with TSC.

Challenges of global surveillance during an influenza pandemic.

Surveillance is an essential foundation for monitoring and evaluating any disease process, and is especially critical when new disease agents appear. The H1N1 influenza pandemic of 2009 tested the capacities of countries to detect, assess, notify and report events as required by the 2005 International Health Regulations (IHR). As detailed in the IHR, the World Health Organization drew on official reports from Member States as well as unofficial sources (e.g., media alerts) to quickly report and disseminate information about the appearance of the novel influenza virus. The pre-existing Global Influenza Surveillance Network for virological surveillance also provided crucial information for rapid development of a vaccine and for detection of changes in the virus. However, the pandemic also highlighted a number of shortcomings in global epidemiological surveillance for respiratory disease. These included the lack of standards for reporting illness, risk factor and mortality data, and a mechanism for systematic reporting of epidemiological data. Such measures would have facilitated direct comparison of data between countries and improved timely understanding of the characteristics and impact of the pandemic. This paper describes the surveillance strategies in place before the pandemic and the methods that were used at global level to monitor the pandemic. Enhancements of global surveillance are proposed to improve preparedness and response for similar events in the future.

Pandemic (H1N1) 2009 influenza in the UK: clinical and epidemiological findings from the first few hundred (FF100) cases.

The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April-June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10-27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0.01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.

The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion.

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.

Rapid evaluation of risk of white particulate matter in blood components by a statewide survey of transfusion reactions.

BACKGROUND: In January 2003, white particulate matter (WPM) was detected in blood components. Because the composition and cause of WPM was not understood at that time, there was uncertainty about whether WPM could endanger patient safety. To investigate possible adverse patient events associated with WPM, transfusion reaction rates were examined. STUDY DESIGN AND METHODS: A questionnaire was distributed to Georgia medical centers. Data collected included the number of components transfused and reported adverse reactions by component type from January 2002 through January 2003, and date, reaction type, and blood supplier for events in January 2003. RESULTS: Of 124 transfusion services contacted, 108 (87%) responded. During the survey period, there were 1213 reported transfusion reactions and 528,412 units transfused, or 2.3 reactions per 1000 units transfused; for RBCs, 2.4 (range, 1.8-3.1); plasma, 1.5 (range, 0.6-3.5); and PLTs, 3.4 (2.1-5.4) per 1000 units. Transfusion reaction rates by component for January 2003 did not differ significantly from the rate for January 2002 or for the calendar year. The 86 reported reactions that occurred in January 2003 were attributed to bacterial contamination (n = 2, 2.3%), other febrile nonhemolytic (n = 49, 57.0%), allergic (n = 14, 16.3%), and "other" reactions (n = 21, 24.4%); the proportions of reaction types did not differ significantly during the month. CONCLUSION: No overall changes in reported adverse reaction rates occurred over the survey period or in the proportion of reaction types during January 2003 when WPM was detected. Statewide surveillance of transfusion reactions could be useful to evaluate potential threats to blood safety.

Simian foamy virus infection in a blood donor.

BACKGROUND: Infections with simian foamy virus (SFV) are widely prevalent in nonhuman primates. SFV infection was confirmed in a worker, occupationally exposed to nonhuman primates, who donated blood after the retrospectively documented date of infection. Human-to-human transmission of SFV through transfusion and its pathogenicity have not been studied. STUDY DESIGN AND METHODS: Recipients of blood from this donor were identified and blood samples from such recipients were tested for SFV infection by Western blot and PCR assay. RESULTS: One recipient of RBCs and another recipient of FFP had died; retroviral infections were not implicated. One platelet recipient could not be tested. Recipients of RBCs (two), a WBC-reduced RBC unit (one), and a platelet unit (one) tested SFV-negative 19 months to 7 years after transfusion. Tested recipients had transfusions 3 to 35 days after blood donation. Samples of one lot of albumin and three lots of plasma protein fraction (manufactured from recovered plasma from two donations) tested negative both for antibodies and for viral RNA. CONCLUSION: SFV transmission through transfusion was not identified among four recipients of cellular blood components from one SFV-infected donor. Derivatives containing plasma from that donor tested negative for SFV.

Emerging infectious disease issues in blood safety.

Improvements in donor screening and testing and viral inactivation of plasma derivatives together have resulted in substantial declines in transfusion-transmitted infections over the last two decades. Most recently, nucleic acid testing techniques have been developed to screen blood and plasma donations for evidence of very recent viral infections that could be missed by conventional serologic tests. Nonetheless, the blood supply remains vulnerable to new and reemerging infections. In recent years, numerous infectious agents found worldwide have been identified as potential threats to the blood supply. Several newly discovered hepatitis viruses and agents of transmissible spongiform encephalopathies present unique challenges in assessing possible risks they may pose to the safety of blood and plasma products.

Transfusion-transmitted malaria in the United States from 1963 through 1999.

BACKGROUND: Transfusion-transmitted malaria is uncommon in the United States. After the report of three cases of complicated Plasmodium falciparum infection acquired by transfusion, we reviewed all cases of transfusion-transmitted malaria reported to the Centers for Disease Control and Prevention (CDC) from 1963 through 1999. METHODS: Information on the patients was from surveillance reports sent to the CDC. Information about the implicated blood donors came from the National Malaria Surveillance System. To determine whether donors should have been excluded from donating blood, we compared their characteristics with the exclusion guidelines of the Food and Drug Administration and the American Association of Blood Banks. RESULTS: Of 93 cases of transfusion-transmitted malaria reported in 28 states, 33 (35 percent) were due to P. falciparum, 25 (27 percent) were due to P. vivax, 25 (27 percent) were due to P. malariae, 5 (5 percent) were due to P. ovale, 3 (3 percent) were mixed infections, and 2 (2 percent) were due to unidentified species. Ten of the 93 patients (11 percent) died. There were potentially 91 donors (in two cases, two patients received blood from the same donor), 67 of whom (74 percent) could be identified as infective. Of 64 implicated donors whose country of origin was reported, 38 (59 percent) were foreign born. Among those for whom complete information was available, 37 of 60 donors (62 percent) would have been excluded from donating according to current guidelines (in place since 1994), and 30 of 48 donors (62 percent) should have been excluded under the guidelines in place at the time of donation. CONCLUSIONS: Careful screening of donors according to the recommended exclusion guidelines remains the best way to prevent transfusion-transmitted malaria.

Risk and management of blood-borne infections in health care workers.

Exposure to blood-borne pathogens poses a serious risk to health care workers (HCWs). We review the risk and management of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in HCWs and also discuss current methods for preventing exposures and recommendations for postexposure prophylaxis. In the health care setting, blood-borne pathogen transmission occurs predominantly by percutaneous or mucosal exposure of workers to the blood or body fluids of infected patients. Prospective studies of HCWs have estimated that the average risk for HIV transmission after a percutaneous exposure is approximately 0.3%, the risk of HBV transmission is 6 to 30%, and the risk of HCV transmission is approximately 1.8%. To minimize the risk of blood-borne pathogen transmission from HCWs to patients, all HCWs should adhere to standard precautions, including the appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Employers should have in place a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place a worker at risk of blood-borne pathogen infection. A sustained commitment to the occupational health of all HCWs will ensure maximum protection for HCWs and patients and the availability of optimal medical care for all who need it.

Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period.

CONTEXT: Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved. OBJECTIVES: To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening. DESIGN AND SETTING: Case study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore. SUBJECTS: The blood donor and the 2 recipients of donor platelets and red blood cells. MAIN OUTCOME MEASURES: Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts. RESULTS: Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States. CONCLUSIONS: Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations. JAMA. 2000;284:210-214

Specific protein-protein interaction between basic helix-loop-helix transcription factors and homeoproteins of the Pitx family.

Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development and cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target for factors of both families. Indeed, pituitary-specific transcription of POMC depends on the action of the homeodomain-containing transcription factor Pitx1 and of bHLH heterodimers containing NeuroD1. We now show lineage-restricted expression of NeuroD1 in pituitary corticotroph cells and a direct physical interaction between bHLH heterodimers and Pitx1 that results in transcriptional synergism. The interaction between the bHLH and homeodomains is restricted to ubiquitous (class A) bHLH and to the Pitx subfamily. Since bHLH heterodimers interact with Pitx factors through their ubiquitous moiety, this mechanism may be implicated in other developmental processes involving bHLH factors, such as neurogenesis and myogenesis.

The nature and frequency of blood contacts among home healthcare workers.

OBJECTIVE: To estimate the frequency of, and assess risk factors for, percutaneous, mucous membrane, and cutaneous blood contacts sustained by healthcare workers (HCWs) during the delivery of infusion therapy and the performance of procedures involving sharp instruments in the home setting. DESIGN: Prospective surveillance of percutaneous, mucous membrane, and cutaneous blood contacts. SETTING: Eleven home healthcare agencies in the United States and Canada from August 1996 through June 1997. PARTICIPANTS: HCWs who provided home infusion therapy or performed procedures using hollow-bore needles and other sharp instruments in the home setting. METHODS: Each participating worker recorded information about the procedures performed and blood contacts experienced during each of his or her home visits for a 2- to 4-week period using standard questionnaires. HCWs also completed questionnaires regarding job duties, reporting of previous occupational blood contacts, and their use of protective barriers in the home setting. RESULTS: Participating HCWs provided information about 33,606 home visits. A total of 19,164 procedures were performed during 14,744 procedure visits. Fifty-three blood contacts occurred during these visits, for a blood-contact rate of 2.8 blood contacts per 1,000 procedures and 0.6 percutaneous injuries per 1,000 procedures with needles or lancets. Gloves were worn for 52%, masks for 5%, gowns for 3%, and protective glasses or goggles for 2% of all procedure visits. HCWs used barriers for 53% of visits during which at least 1 procedure was performed and for 27% of other visits. CONCLUSIONS: HCWs involved in home health care are at risk for blood contact. Infection control barrier use was low in our study. The majority of skin contacts could have been prevented by glove use.

Surveillance for bloodborne infections.

At the close of the 20th century, the blood supply in the U.S. is among the safest in the world. Multifaceted and overlapping strategies that include comprehensive donor history-taking and screening (soon to include nucleic acid testing for HCV and HIV), and viral inactivation of plasma derivatives have resulted in significant declines in transfusion-transmitted infections. Nonetheless, we and our blood supply remain vulnerable to new or re-emerging infections as a consequence of changes in human behavior and demographics, improvements in technology and industry, economic development and land use, and microbial change. The second phase of CDC's strategic plan to improve our national capacity against emerging infectious diseases targets diseases transmitted through blood and blood products as one of its nine special focus areas. One of our mainstays against emerging threats must include surveillance, integrated with a multi-disciplinary approach that includes epidemiology and laboratory sciences. Enhanced surveillance can play an important role in helping to ensure the continued safety of blood and plasma products.

Oversight and monitoring of blood safety in the United States.

The US blood safety vigilance system is composed of a network of interwoven programs, now organized under a formal structure, with the Assistant Secretary of Health and DHHS Blood Safety Committee bearing overall responsibility. It takes advantage of the breadth of expertise and close collaborative relationship of transfusion medicine and infectious disease scientists within and outside of the government. Core elements include an array of ongoing surveillance programs for monitoring established as well as new and emerging infectious agents that may pose a risk to blood safety, and the existence of historical and contemporary repositories of donor and recipient specimens that enable rapid investigation of putative new risks. This report summarizes the historical events that shaped the US blood safety oversight system, reviews the current organization and decision-making processes related to blood safety issues, and highlights key surveillance systems and research programs which monitor the US and global blood supplies for known and potential emerging risks.

An investigation into the possibility of transmission of tick-borne pathogens via blood transfusion. Transfusion-Associated Tick-Borne Illness Task Force.

BACKGROUND: Tick-borne illnesses were diagnosed in a group of National Guard members, including some who had donated blood a few days before the onset of symptoms. A voluntary recall of those blood components was issued and a multistate investigation was conducted to determine if transfusion-transmitted illness had occurred. STUDY DESIGN AND METHODS: Donors and recipients were asked to complete questionnaires regarding symptoms and risk factors for infection and to provide blood samples for laboratory analysis. RESULTS: Among National Guard personnel who donated blood, 12 individuals were found to have a confirmed or probable case of Rocky Mountain spotted fever or ehrlichiosis. A total of 320 units (platelets or packed red cells) from 377 donors were transfused into 129 recipients. Although 10 recipients received units from National Guard personnel with confirmed or probable infection, none became ill. CONCLUSION: Transfusion-transmitted illness did not occur. Despite the awareness of the risk for tick-borne diseases and the use of tick-preventive measures, many National Guard personnel reported exposure to ticks. In addition to augmenting current tick-preventive measures, scheduling blood drives before rather than after field exercises could further reduce the potential for transmission of tick-borne pathogens.

Hindlimb patterning and mandible development require the Ptx1 gene.

The restricted expression of the Ptx1 (Pitx1) gene in the posterior half of the lateral plate mesoderm has suggested that it may play a role in specification of posterior structures, in particular, specification of hindlimb identity. Ptx1 is also expressed in the most anterior ectoderm, the stomodeum, and in the first branchial arch. Ptx1 expression overlaps with that of Ptx2 in stomodeum and in posterior left lateral plate mesoderm. We now show that targeted inactivation of the mouse Ptx1 gene severely impairs hindlimb development: the ilium and knee cartilage are absent and the long bones are underdeveloped. Greater reduction of the right femur size in Ptx1 null mice suggests partial compensation by Ptx2 on the left side. The similarly sized tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice. The hindlimb defects appear to be, at least partly, due to abnormal chondrogenesis. Since the most affected structures derive from the dorsal side of hindlimb buds, the data suggest that Ptx1 is responsible for patterning of these dorsal structures and that as such it may control development of hindlimb-specific features. Ptx1 inactivation also leads to loss of bones derived from the proximal part of the mandibular mesenchyme. The dual role of Ptx1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolution.

Surveillance for transfusion-transmitted viral infections in the United States.

Surveillance is part of a multi-faceted programme to monitor the safety of the U. S. blood supply. The Centers for Disease Control and Prevention administers several national surveillance programmes, including pathogen- and disease-specific systems (e.g. human immunodeficiency virus, hepatitis) and programmes that focus on donors and recipients of blood and plasma products (e.g. persons with haemophilia). Data collected in these systems can be used to monitor temporal and epidemiological trends, identify risk factors for infection, facilitate identification and investigation of potential outbreaks, and evaluate intervention and prevention strategies.

Blood safety.

Since blood is a biologic product, it is unlikely that the risk for transfusion-transmitted infection will ever be reduced to zero. The approach to emerging infections associated with transfusion of blood and blood products includes assessing the transmissibility of the agent by this route; developing effective prevention strategies, including screening tests and donor deferral policies; improving viral and bacterial inactivation procedures; and surveillance for known, as well as emerging and poorly characterized, transfusion-transmitted agents. Vigilance is needed to help ensure proper balance between safety and the availability of blood. Finally, vigilance needs to extend to the developing world, where the basic elements to reduce transfusion-transmitted infections and systems of disease surveillance are often not available.