Integrating Patient-Centered Electronic Health Record Communication Training into Resident Onboarding: Curriculum Development and Post-Implementation Survey Among Housestaff.

BACKGROUND: Electronic health record (EHR) use can enhance or undermine the ability of providers to deliver effective, humanistic patient-centered care. Given patient-centered care has been found to positively impact patient health outcomes, it is critical to provide formal education on patient-centered EHR communication skills. Unfortunately, despite increasing worldwide EHR adoption, few institutions educate trainees on EHR communication best practices. OBJECTIVE: The goal of this research was to develop and deliver mandatory patient-centered EHR training to all incoming housestaff at the University of Chicago. METHODS: We developed a brief patient-centered EHR use curriculum highlighting best practices based on a literature search. Training was embedded into required EHR onboarding for all incoming housestaff (interns, residents, and fellows) at the University of Chicago in 2015 and was delivered by institutional Clinical Applications Trainers. An 11-item posttraining survey consisting of ten 5-point Likert scale questions and 1 open-ended question was administered. Responses at the high end of the scale were grouped to dichotomize data. RESULTS: All 158 of the incoming 2015 postgraduate trainees participated in training and completed surveys (158/158, 100.0%). Just over half (86/158, 54.4%) were interns and the remaining were residents and fellows (72/158, 45.6%). One-fifth of respondents (32/158, 20.2%) were primary care trainees (defined as internal medicine, pediatric, and medicine-pediatric trainees), and the remaining 79.7% (126/158) were surgical or specialty trainees. Self-perceived pre- versus posttraining knowledge of barriers, best practices, and ability to implement patient-centered EHR skills significantly increased (3.1 vs 3.9, P<.001 for all). Most felt training was effective (90.5%), should be required (86.7%), and would change future practice as a result (70.9%). The only significant difference between intern and resident/fellow responses was prior knowledge of patient-centered EHR use barriers; interns endorsed higher prior knowledge than resident peers (3.27 vs 2.94 respectively, P=.03). Response comparison of specialty or surgical trainees (n=126) to primary care trainees (n=32) showed no significant differences in prior knowledge of barriers (3.09 vs 3.22, P=.50), of best practices (3.08 vs 2.94, P=.37), or prior ability to implement best practices (3.11 vs 2.84, P=.15). Primary care trainees had larger increases posttraining than surgical/specialty peers in knowledge of barriers (0.8 vs 0.7, P=.62), best practices (1.1 vs 0.8, P=.08), and ability to implement best practices (1.1 vs 0.7, P=.07), although none reached statistical significance. Primary care trainees also rated training as more effective (4.34 vs 4.09, P=.03) and felt training should be required (4.34 vs 4.09, P=.10) and would change their future practice as a result (4.13 vs 3.73, P=.02). CONCLUSIONS: Embedding EHR communication skills training into required institutional EHR training is a novel and effective way to teach key EHR skills to trainees. Such training may help ground trainees in best practices and contribute to cultivating an institutional culture of humanistic, patient-centered EHR use.

Therapeutic benefits of cannabis: a patient survey.

Clinical research regarding the therapeutic benefits of cannabis ("marijuana") has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai'i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai'i. No serious adverse effects were reported. These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety. Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.

Randomised controlled trial of a brief alcohol intervention in a general hospital setting.

BACKGROUND: The evidence suggests that brief alcohol-focused interventions, directed at hazardous and harmful drinkers in non-specialist settings such as primary care are effective in reducing alcohol consumption. However, there is a need for further research in the hospital setting. This is a randomised controlled trial to investigate the effectiveness of a 10-minute brief intervention amongst 'at risk' drinkers admitted to general hospital wards. Unlike some previous trials, this trial is randomised, used blinded assessors, includes an intention-to-treat analysis, included female subjects and excluded people with alcohol dependence. METHODS: A total of 250 'at risk' drinkers admitted to King's College Hospital were identified using the Alcohol Use Disorders Identification Test (AUDIT). Some 154 subjects entered the study and were randomly allocated to the control and intervention groups. Subjects in the control group received no advice about their drinking whilst subjects in the intervention group received 10 minutes of simple advice on reducing alcohol consumption. Recruitment took place between 1995 and 1997. The primary outcome was the AUDIT questionnaire at 12 months. Secondary outcomes were a previous week's Drinks Diary, questionnaires (General Health Questionnaire, Alcohol Problems Questionnaire and the Severity of Alcohol Dependence Questionnaire) and laboratory blood tests (gamma glutamyl transferase, mean cell volume and haemoglobin). RESULTS: At 3-month and 12-month follow-up, all participants were included in the intention-to-treat analysis. At both time points there was no evidence of an intervention effect that could be attributed to the brief intervention. Both the intervention and control groups had an improved AUDIT score and reduced levels of alcohol consumption as measured by a subjective Drinks Diary at 3 months which was maintained at 12 months. CONCLUSIONS: This study has added further evidence on brief interventions in the hospital setting. In contrast to the recent Cochrane review by McQueen et al., the results of this study do not support the effectiveness of a brief alcohol intervention in general hospital wards. However our study was underpowered and there were flaws in the statistical analyses, and these limitations temper the strength of our conclusions.

Elite athletes travelling to international destinations >5 time zone differences from their home country have a 2-3-fold increased risk of illness.

BACKGROUND: Illness accounts for a significant proportion of consultations with a team physician travelling with elite athletes. OBJECTIVE: To determine if international travel increases the incidence of illness in rugby union players participating in a 16-week tournament. SETTING: 2010 Super 14 Rugby Union tournament. PARTICIPANTS: 259 elite rugby players from eight teams were followed daily over the 16-week competition period (22 676 player-days). ASSESSMENT: Team physicians completed a logbook detailing the daily squad size and illness in any player (system affected, final diagnosis, type and onset of symptoms, training/match days lost and suspected cause) with 100% compliance. Time periods during the tournament were divided as follows: located and playing in the home country before travelling (baseline), located and playing abroad in countries >5 h time zone difference (travel) and located back in the home country following international travel (return). MAIN OUTCOME MEASUREMENT: Incidence of illness (illness per 1000 player-days) during baseline, travel and return. RESULTS: The overall incidence of illness in the cohort was 20.7 (95% CI 18.5 to 23.1). For all teams, the incidence of illness according to location and travelling was significantly higher in the time period following international travel (32.6; 95% CI 19.6 to 53.5) compared with the baseline (15.4; 95% CI 8.7 to 27.0) or after returning to their home country (10.6; 95% CI 6.1 to 18.2). CONCLUSIONS: There is a higher incidence of illness in athletes following international travel to a foreign country that is >5 h time difference and this returns to baseline on return to the home country.

Illness during the 2010 Super 14 Rugby Union tournament - a prospective study involving 22 676 player days.

BACKGROUND: Illness accounts for a significant proportion of consultations with a team physician travelling with elite athletes. OBJECTIVE: To determine the incidence, type, cause and consequences of illness in Rugby Union players participating in a 16-week tournament. SETTING: 8 teams participating in the 2010 Super 14 Rugby tournament Participants A cohort of 259 elite rugby players from eight teams was recruited. ASSESSMENT: All players were followed daily over the 16-week competition period (22 676 player days). Each day, team physicians completed an illness log with 100% compliance. Information included the daily squad size and illness details including system affected, final diagnosis, type and onset of symptoms, training/match days lost and suspected cause. MAIN OUTCOME MEASUREMENT: Incidence of illness (illness per 1000 player days). RESULTS: The incidence of illness in the cohort was 20.7/1000 player days (95% CI 18.5 to 23.1) with the highest incidence of illness in the respiratory system (6.4: 95% CI 5.5 to 7.3), gastrointestinal system (5.6: 95% CI 4.9 to 6.6) and the skin and subcutaneous tissue (4.6; 95% CI 4.0 to 5.4). Infections accounted for 54.5% of all illness and 26.1% of illness resulted in time loss of ≥1 day. In over 50% of illnesses, symptoms were present for ≥1 day before being reported to the team physician. CONCLUSION: Infective illness involving the respiratory tract and gastrointestinal tract together with dermatological illness was common in elite rugby players participating in this international tournament. A delay in reporting of symptoms >24 h could have important clinical implications in player medical care.

Normal and abnormal development of the intrapericardial arterial trunks in humans and mice.

AIMS: The definitive cardiac outflow channels have three components: the intrapericardial arterial trunks; the arterial roots with valves; and the ventricular outflow tracts (OFTs). We studied the normal and abnormal development of the most distal of these, the arterial trunks, comparing findings in mice and humans. METHODS AND RESULTS: Using lineage tracing and three-dimensional visualization by episcopic reconstruction and scanning electron microscopy, we studied embryonic day 9.5-12.5 mouse hearts, clarifying the development of the OFTs distal to the primordia of the arterial valves. We characterize a transient aortopulmonary (AP) foramen, located between the leading edge of a protrusion from the dorsal wall of the aortic sac and the distal margins of the two outflow cushions. The foramen is closed by fusion of the protrusion, with its cap of neural crest cells (NCCs), with the NCC-filled cushions; the resulting structure then functioning transiently as an AP septum. Only subsequent to this closure is it possible to recognize, more proximally, the previously described AP septal complex. The adjacent walls of the intrapericardial trunks are derived from the protrusion and distal parts of the outflow cushions, whereas the lateral walls are formed from intrapericardial extensions of the pharyngeal mesenchyme derived from the second heart field. CONCLUSIONS: We provide, for the first time, objective evidence of the mechanisms of closure of an AP foramen that exists distally between the lumens of the developing intrapericardial arterial trunks. Our findings provide insights into the formation of AP windows and the variants of common arterial trunk.

Isolated popliteus rupture at the musculo-tendinous junction.

We report the case of a 23-year-old professional senior international rugby union player who sustained a lateral blow to his semiflexed knee during a competitive game. Initial clinical examination was unremarkable apart from some posterolateral tenderness. A magnetic resonance imaging scan showed an isolated popliteus tendon rupture at the musculo-tendinous junction. After 5 weeks of focused rehabilitation and graduated training, he was able to resume his playing career and resumed his international playing career later that season. At the time of reporting, he has completed a full domestic and international season without any sequelae from the injury. This report highlights the rarity of such an injury, especially at the musculo-tendinous junction, and sets out a detailed rehabilitation program that has enabled the patient in question to resume his playing career.

Left cardiac isomerism in the Sonic hedgehog null mouse.

Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from the loss of the effects of Shh in the establishment of laterality, combined with a reduced contribution made by cells derived from the second heart field.

Dual role for neural crest cells during outflow tract septation in the neural crest-deficient mutant Splotch(2H).

Splotch(2H) (Sp(2H)) is a well-recognized mouse model of neural crest cell (NCC) deficiency that develops a spectrum of cardiac outflow tract malformations including common arterial trunk, double outlet right ventricle, ventricular septal defects and pharyngeal arch artery patterning defects, as well as defects in other neural-crest derived organ systems. These defects have been ascribed to reduced NCC in the pharyngeal and outflow regions. Here we provide a detailed map of NCC within the pharyngeal arches and outflow tract of Sp(2H)/Sp(2H) embryos and fetuses, relating this to the development of the abnormal anatomy of these structures. In the majority of Sp(2H)/Sp(2H) embryos we show that deficiency of NCC in the pharyngeal region results in a failure to stabilize, and early loss of, posterior pharyngeal arch arteries. Furthermore, marked reduction in the NCC-derived mesenchyme in the dorsal wall of the aortic sac disrupts fusion with the distal outflow tract cushions, preventing the initiation of outflow tract septation and resulting in common arterial trunk. In around 25% of Sp(2H)/Sp(2H) embryos, posterior arch arteries are stabilized and fusion occurs between the dorsal wall of the aortic sac and the outflow cushions, initiating outflow tract septation; these embryos develop double outlet right ventricle. Thus, NCC are required in the pharyngeal region both for stabilization of posterior arch arteries and initiation of outflow tract septation. Loss of NCC also disrupts the distribution of second heart field cells in the pharyngeal and outflow regions. These secondary effects of NCC deficiency likely contribute to the overall outflow phenotype, suggesting that disrupted interactions between these two cell types may underlie many common outflow defects.

Maximum rates of cooling by three programmable freezers, and the potential relevance to sperm cryopreservation.

Maximum rates of cooling for the Asymptote EF 100 and the Cryologic CL8800 temperature controller with either a standard or fast chamber were determined and viewed in the context of sperm cryopreservation. All three systems use liquid nitrogen to cool the plate or chamber which would hold the sample, opposed by a variable amount of heat from an internal heater. Maximum rates of cooling for all systems were a function of the temperature gradient between the liquid nitrogen and the plate/chamber and at a plate/chamber temperature of 15 degrees C were 16.5 degrees C/min, 13.3 degrees C/min and 8.0 degrees C/min for the Asymptote EF100, Cryologic fast and slow chambers respectively. These machines are not suited to the freezing of sperm from species requiring rapid rates of cooling, an important consideration when planning to purchase a piece of equipment for this application, and scientists are advised to discuss specifically their requirements with prospective suppliers.

Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart.

Cells migrating from the neural crest are known to septate the outflow tract of the developing heart, and to contribute to the formation of the arterial valves, their supporting sinuses, the coronary arteries and cardiac neural ganglia. Neural crest cells have also been suggested to contribute to development of the venous pole of the heart, but the extent and fate of such cells remains unclear. In this study, in the mouse, it is shown that cells from the neural crest contribute to the parasympathetic and, to a lesser extent, the sympathetic innervation of the venous pole of the heart. Nerves within the venous pole of the heart are shown to be of mixed origin, with some being derived from the neural crest, while others have an alternative origin, presumably placodal. The neurons innervating the nodal tissue, which can exert chronotropic effects on cardiac conduction, are shown not to be derived from the neural crest. In particular, no evidence was found to support previous suggestions that cells from the neural crest make a direct contribution to the myocardial atrioventricular conduction axis, although a small subset of these cells do co-localize with the developing left bundle branch. We have therefore confirmed that cells from the neural crest migrate to the venous pole of the heart, and that their major role is in the development of the parasympathetic innervation. In addition, in some embryos, a population of cells derived from the neural crest persist in the leaflets of the atrioventricular valves, but their role in subsequent development remains unknown.

Rumination-focused cognitive behaviour therapy for residual depression: a case series.

The treatment of chronic and recurrent depression is a priority for the development of new interventions. The maintenance of residual symptoms following acute treatment for depression is a risk factor for both chronic depression and further relapse/recurrence. This open case series provides the first data on a cognitive-behavioural treatment for residual depression that explicitly targets depressive rumination. Rumination has been identified as a key factor in the onset and maintenance of depression, which is found to remain elevated following remission from depression. Fourteen consecutively recruited participants meeting criteria for medication--refractory residual depression [Paykel, E.S., Scott, J., Teasdale, J.D., Johnson, A.L., Garland, A., Moore, R. et al., 1999. Prevention of relapse in residual depression by cognitive therapy--a controlled trial. Archives of General Psychiatry 56, 829-835] were treated individually for up to 12 weekly 60-min sessions. Treatment specifically focused on switching patients from less helpful to more helpful styles of thinking through the use of functional analysis, experiential/imagery exercises and behavioural experiments. Treatment produced significant improvements in depressive symptoms, rumination and co-morbid disorders: 71% responded (50% reduction on Hamilton Depression Rating Scale) and 50% achieved full remission. Treating depressive rumination appears to yield generalised improvement in depression and co-morbidity. This study provides preliminary evidence that rumination-focused CBT may be an efficacious treatment for medication--refractory residual depression.

The benefits and limitations of the sperm quality analyzer IIB in assessing porcine sperm motility.

The Sperm Quality Analyzer (SQA) IIB, a member of the SQA-II family of machines which uses the scatter of light by sperm as an indicator of sperm motility, was systematically evaluated as a means of analyzing objectively the motility of porcine epididymal sperm. The sperm motility (%) and the Sperm Motility Index (SMI) are calculated by the machine using pre-programmed algorithms designed for human sperm. The machine performed well and was able to detect changes in sperm motility under experimental conditions. However, two major limitations of this machine were identified, (i) the readings obtained were influenced by the concentration of the sperm suspension despite the actual sperm motility remaining constant, and (ii) the machine was unable to differentiate between progressive and non-progressive motility. It should therefore be recognized that (a) the sperm concentration must be kept constant in studies in vitro if differences between treatment groups are to be identified, and (b) the inability to separate progressive motility from that of total motility will restrict the usefulness of this and similar machines to studies monitoring changes in total motility alone.

Nuchal edema and venous-lymphatic phenotype disturbance in human fetuses and mouse embryos with aneuploidy.

OBJECTIVE: Nuchal edema (NE) is a clinical indicator for aneuploidy, cardiovascular anomalies, and several genetic syndromes. Its etiology, however, is unknown. In the nuchal area, the endothelium of the jugular lymphatic sacs (JLS) develops by budding from the blood vascular endothelium of the cardinal veins. Abnormal distension of the jugular sacs is associated with NE. We hypothesize that a disturbed lymphatic endothelial differentiation and sac formation causes NE. We investigated endothelial differentiation of the jugular lymphatic system in human and mouse species with NE. METHODS: Aneuploid human fetuses (trisomy 21; trisomy 18) were compared with euploid controls (gestational age 12 to 18 weeks). Trisomy 16 mouse embryos were compared with wild type controls (embryonic day 10 to 18). Trisomy 16 mice are considered an animal model for human trisomy 21. Endothelial differentiation was investigated by immunohistochemistry using lymphatic markers (prox-1, podoplanin, lymphatic vessel endothelial hyaluronan receptor [LYVE]-1) and en blood vessel markers (neuropilin [NP]-1 and ligand vascular endothelial growth factor [VEGF]-A). Smooth muscle actin (SMA) was included as a smooth muscle cell marker. RESULTS: We report a disturbed venous-lymphatic phenotype in aneuploid human fetuses and mouse embryos with enlarged jugular sacs and NE. Our results show absent or diminished expression of the lymphatic markers Prox-1 and podoplanin in the enlarged jugular sac, while LYVE-1 expression was normal. Additionally, the enlarged JLS showed blood vessel characteristics, including increased NP-1 and VEGF-A expression. The lumen contained blood cells and smooth muscle cells lined the wall. CONCLUSION: A loss of lymphatic identity seems to be the underlying cause for clinical NE. Also, abnormal endothelial differentiation provides a link to the cardiovascular anomalies associated with NE.

Increased NCAM expression and vascular development in trisomy 16 mouse embryos: relationship with nuchal translucency.

Increased nuchal translucency in the human fetus is associated with chromosomal abnormalities, enlarged jugular lymphatic sacs, cardiac defects and changed flow through the ductus venosus. The developmental background of this nuchal edema in relation to the associated anomalies remains elusive. We studied the morphologic correlation between neurogenesis and vasculogenesis in neck, heart, and ductus venosus region of wild type and trisomy 16 mice embryos (E10- E18), using an antibody against Neural Cell Adhesion Molecule (NCAM). Trisomy 16 mice are a model for the above described human phenotype. From E12 trisomy 16 mice showed an altered arrangement of cranial nerves IX, X and XI, which are positioned between the carotid artery, jugular vein and enlarged lymphatic sac. The vagal nerve was significantly smaller, compared with wild type embryos. NCAM was over expressed in both neuronal and cardiovascular structures in trisomy 16 mice, being particularly prominent in the 4th and 6th pharyngeal arch arteries, and the ductus venosus. In the 4th and 6th pharyngeal arch arteries, NCAM over expression was located to the part of the vessel wall that is closely related to the vagal and recurrent nerve. In case of 4th pharyngeal arch artery abnormalities NCAM expression, on the other hand, was reduced. In conclusion, the interaction between neurogenesis and vasculogenesis is disturbed in the trisomy 16 mouse model, and might be a common denominator in the spectrum of anomalies associated with increased nuchal translucency.

Development of the atrioventricular valves: clinicomorphological correlations.

The atrioventricular valves are formed from a complex arrangement of an annulus and leaflets, supported by a subvalvar apparatus that is composed of tendinous cords and papillary muscles. Although much has been said and written about their development, the exact nature of the process has yet to be fully elucidated. We believe that this is vital, since unraveling this complex process holds the key to the understanding of many of the congenital malformations that may afflict the valves.

Reconstruction of the patterns of gene expression in the developing mouse heart reveals an architectural arrangement that facilitates the understanding of atrial malformations and arrhythmias.

Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has continued to be the source of disagreement. Seeking to resolve these controversies, we made three-dimensional reconstructions of the myocardial components of the developing atrium, identifying domains on the basis of differential expression of myocardial markers, connexin40, and natriuretic precursor peptide A. These reconstructions, made from serial sections of mouse embryos, show that from the outset of atrial development, the systemic and pulmonary veins are directly connected to the atrium. Relative to the systemic junctions, however, the pulmonary venous junction appears later. Our experience shows that three-dimensional reconstructions have three advantages. First, they provide clear access to the combined morphological and molecular data, allowing clarification and verification of morphogenetic concepts for nonmorphological experts and setting the scene for further discussion. Second, they demonstrate that, from the outset, the myocardium surrounding the pulmonary veins is distinct from that clothing the systemic venoatrial junctions. Third, they reveal an anatomical and molecular continuity between the entrance of the systemic venous tributaries, the internodal atrial myocardium, and the atrioventricular region. All these regions are derived from primary myocardium, providing a molecular basis for the observed nonrandom distribution of focal right atrial tachycardias.

Lineage and morphogenetic analysis of the cardiac valves.

We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development.