Rehabilitation Treatment Specification System: Methodology to Identify and Describe Unique Targets and Ingredients.

Although significant advances have been made in measuring the outcomes of rehabilitation interventions, comparably less progress has been made in measuring the treatment processes that lead to improved outcomes. A recently developed framework called the Rehabilitation Treatment Specification System (RTSS) has potential to identify which clinician actions (ie, ingredients) actively improve specific patient functions (ie, targets). However, the RTSS does not provide methodology for standardly identifying specific unique targets or ingredients. Without a method to evaluate the uniqueness of an individual target or ingredient, it is difficult to know whether variations in treatment descriptions are synonymous (ie, different words describing the same treatment) or meaningfully different (eg, different words describing different treatments or variations of the same treatment). A recent project used vocal rehabilitation ingredients and targets to create RTSS-based lists of unique overarching target and ingredient categories with underlying dimensions describing how individual ingredients and targets vary within those categories. The primary purpose of this article is to describe the challenges encountered during the project and the methodology developed to address those challenges. Because the methodology was based on the RTSS's broadly applicable framework, it can be used across all areas of rehabilitation regardless of the discipline (speech-language pathology, physical therapy, occupational therapy, psychology, etc) or impairment domain (language, cognition, ambulation, upper extremity training, etc). The resulting standard operationalized lists of targets and ingredients have high face and content validity. The lists may also facilitate implementation of the RTSS in research, education, interdisciplinary communication, and everyday treatment.

Stochastic programming for outpatient scheduling with flexible inpatient exam accommodation.

This study is concerned with the determination of an optimal appointment schedule in an outpatient-inpatient hospital system where the inpatient exams can be cancelled based on certain rules while the outpatient exams cannot be cancelled. Stochastic programming models were formulated and solved to tackle the stochasticity in the procedure durations and patient arrival patterns. The first model, a two-stage stochastic programming model, is formulated to optimize the slot size. The second model further optimizes the inpatient block (IPB) placement and slot size simultaneously. A computational method is developed to solve the second optimization problem. A case study is conducted using the data from Magnetic Resonance Imaging (MRI) centers of Lahey Hospital and Medical Center (LHMC). The current schedule and the schedules obtained from the optimization models are evaluated and compared using simulation based on FlexSim Healthcare. Results indicate that the overall weighted cost can be reduced by 11.6% by optimizing the slot size and can be further reduced by an additional 12.6% by optimizing slot size and IPB placement simultaneously. Three commonly used sequencing rules (IPBEG, OPBEG, and a variant of ALTER rule) were also evaluated. The results showed that when optimization tools are not available, ALTER variant which evenly distributes the IPBs across the day has the best performance. Sensitivity analysis of weights for patient waiting time, machine idle time and exam cancellations further supports the superiority of ALTER variant sequencing rules compared to the other sequencing methods. A Pareto frontier was also developed and presented between patient waiting time and machine idle time to enable medical centers with different priorities to obtain solutions that accurately reflect their respective optimal tradeoffs. An extended optimization model was also developed to incorporate the emergency patient arrivals. The optimal schedules from the extended model show only minor differences compared to those from the original model, thus proving the robustness of the scheduling solutions obtained from our optimal models against the impacts of emergency patient arrivals.

HIGHLIGHTS: Timestamped operational data was analyzed to identify sources of uncertainty and delays. Stochastic programming models were developed to optimize slot size and inpatient block placement. A case study showed that the optimized schedules can reduce overall costs by 23%. Distributing inpatient and outpatient slots evenly throughout the day provides the best performance. A Pareto frontier was developed to allow practitioners to choose their own best tradeoffs between multiple objectives.

How We Do It: Operationalizing Just Culture in a Radiology Department.

OBJECTIVE. The purpose of this article is to describe how establishing routine practice sessions facilitates adoption by modality operations managers of the just culture model of error management in a radiology department. CONCLUSION. Implementation of ongoing just culture training among radiology operations managers can help them approach uniformity, equity, and transparency in managing errors. Managers see the just culture method as an effective tool that helps improve the safety of patient care.

A randomized trial of phenylephrine infusion versus bolus dosing for nausea and vomiting during Cesarean delivery in obese women.

PURPOSE: Hypotension is common after spinal anesthesia for Cesarean delivery. It is associated with nausea, vomiting, and fetal acidosis. Previous research on phenylephrine excluded obese subjects. We compared the incidence of intraoperative nausea and vomiting (IONV) in obese patients who received a prophylactic phenylephrine infusion vs those who received bolus dosing for the treatment of spinal-induced hypotension. METHODS: In this multicentre, double-blinded randomized controlled trial, 160 obese women undergoing elective Cesarean delivery under spinal anesthesia were randomized to receive a prophylactic phenylephrine infusion initiated at 50 µg·min-1 (and titrated according to a predefined algorithm) or 100 µg phenylephrine boluses to treat hypotension. Maternal systolic blood pressure was maintained within 20% of baseline. The primary study outcome was the incidence of IONV. RESULTS: Intraoperative nausea and vomiting were significantly reduced in the infusion group compared to the bolus group (46% vs 75%, respectively; relative risk [RR], 0.61; 95% confidence interval [CI], 0.47 to 0.80; P < 0.001). This was associated with significantly reduced need for intraoperative rescue antiemetics (26% vs 42%, respectively; RR, 0.62; 95% CI, 0.40 to 0.97; P = 0.04), but no difference in the incidence of vomiting. Postoperative vomiting at two hours was reduced in the infusion group (11% vs 25%; RR, 0.44; 95% CI, 0.21 to 0.90; P = 0.02);however, there were no differences in the incidence or severity of postoperative nausea, need for rescue antiemetics at two hours and 24 hr, or the incidence of postoperative vomiting at 24 hr. CONCLUSION: In obese women undergoing Cesarean delivery with spinal anesthesia, prophylactic phenylephrine infusion was associated with less intraoperative nausea, less need for rescue antiemetics, and reduced early postoperative vomiting. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01481740). Registered 22 July 2011.

Rehabilitation Treatment Specification System for Voice Therapy: Application to Everyday Clinical Care.

PURPOSE: Rehabilitation intervention descriptions often do not explicitly identify active ingredients or how those ingredients lead to changes in patient functioning. The Rehabilitation Treatment Specification System (RTSS) provides guidance to identify the critical aspects of any rehabilitation therapy and supported the development of standardly named ingredients and targets in voice therapy (Rehabilitation Treatment Specification System for Voice Therapy [RTSS-Voice]). This study sought to test the content validity of the RTSS-Voice and determine if the RTSS-Voice can be used to identify commonalities and differences in treatment (criterion validity) across clinicians in everyday clinical practice. METHOD: Five speech-language pathologists from different institutions videotaped one therapy session for 59 patients diagnosed with a voice or upper airway disorder. Specifications were created for each video, and iterative rounds of revisions were completed with the treating clinician and two RTSS experts until consensus was reached on each specification. RESULTS: All 59 sessions were specified without the addition of any targets or ingredients. There were two frequent targets: (a) increased volition and (b) decreased strained voice quality. There were three frequent ingredients: (a) information regarding the patient's capability and motivation to perform a therapeutic behavior, (b) knowledge of results feedback, and (c) opportunities to practice voicing with improved resonance and mean airflow. Across sessions treating vocal hyperfunction, there was large variability across clinicians regarding the types and number of treatment components introduced, types of feedback provided, and vocal practice within spontaneous speech and negative practice. CONCLUSIONS: The RTSS and the RTSS-Voice demonstrated strong content validity, as they comprehensively characterized 59 therapy sessions. They also demonstrated strong criterion validity, as commonalities and differences were identified in everyday voice therapy for vocal hyperfunction across multiple clinicians. Future work to translate RTSS principles and RTSS-Voice terms into clinical documentation can help to understand how clinician and patient variability impacts outcomes and bridge the research-practice gap. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24796875.

Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq.

Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment. Here, as a step toward this goal for neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. We identified 1,917 medically relevant genes expressing multiple isoforms in the frontal cortex where 1,018 had multiple isoforms with different protein-coding sequences. Of these 1,018 genes, 57 are implicated in brain-related diseases including major depression, schizophrenia, Parkinson's disease and Alzheimer disease. Our study also uncovered 53 new RNA isoforms in medically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. We also reported on five mitochondrially encoded, spliced RNA isoforms. We found 99 differentially expressed RNA isoforms between cases with Alzheimer disease and controls.

The Trypanosoma cruzi protease cruzain mediates immune evasion.

Trypanosoma cruzi is the causative agent of Chagas' disease. Novel chemotherapy with the drug K11777 targets the major cysteine protease cruzain and disrupts amastigote intracellular development. Nevertheless, the biological role of the protease in infection and pathogenesis remains unclear as cruzain gene knockout failed due to genetic redundancy. A role for the T. cruzi cysteine protease cruzain in immune evasion was elucidated in a comparative study of parental wild type- and cruzain-deficient parasites. Wild type T. cruzi did not activate host macrophages during early infection (<60 min) and no increase in ∼P iκB was detected. The signaling factor NF-κB P65 colocalized with cruzain on the cell surface of intracellular wild type parasites, and was proteolytically cleaved. No significant IL-12 expression occurred in macrophages infected with wild type T. cruzi and treated with LPS and BFA, confirming impairment of macrophage activation pathways. In contrast, cruzain-deficient parasites induced macrophage activation, detectable iκB phosphorylation, and nuclear NF-κB P65 localization. These parasites were unable to develop intracellularly and survive within macrophages. IL 12 expression levels in macrophages infected with cruzain-deficient T. cruzi were comparable to LPS activated controls. Thus cruzain hinders macrophage activation during the early (<60 min) stages of infection, by interruption of the NF-κB P65 mediated signaling pathway. These early events allow T. cruzi survival and replication, and may lead to the spread of infection in acute Chagas' disease.

Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target.

Inhibition of the Trypanosoma cruzi cysteine protease cruzain has been proposed as a therapeutic approach for the treatment of Chagas' disease. Among the best-studied cruzain inhibitors to date is the vinylsulfone K777 (1), which has proven effective in animal models of Chagas' disease. Recent structure-activity studies aimed at addressing potential liabilities of 1 have now produced analogues such as N-[(2S)-1-[[(E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]amino]-3-(4-methylphenyl)-1-oxopropan-2-yl]pyridine-4-carboxamide (4), which is trypanocidal at ten-fold lower concentrations than for 1. We now find that the trypanocidal activity of 4 derives primarily from the inhibition of T. cruzi 14-α-demethylase (TcCYP51), a cytochrome P450 enzyme involved in the biosynthesis of ergosterol in the parasite. Compound 4 also inhibits mammalian CYP isoforms but is trypanocidal at concentrations below those required to significantly inhibit mammalian CYPs in vitro. A chemical-proteomics approach employing an activity-based probe derived from 1 was used to identify mammalian cathepsin B as a potentially important off-target of 1 and 4. Computational docking studies and the evaluation of truncated analogues of 4 reveal structural determinants for TcCYP51 binding, information that will be useful in further optimization of this new class of inhibitors.

Using deep long-read RNAseq in Alzheimer's disease brain to assess medical relevance of RNA isoform diversity.

Due to alternative splicing, human protein-coding genes average over eight RNA isoforms, resulting in nearly four distinct protein coding sequences per gene. Long-read RNAseq (IsoSeq) enables more accurate quantification of isoforms, shedding light on their specific roles. To assess the medical relevance of measuring RNA isoform expression, we sequenced 12 aged human frontal cortices (6 Alzheimer's disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. Our study uncovered 53 new high-confidence RNA isoforms in medically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. Specific examples include WDR4 (61%; microcephaly), MYL3 (44%; hypertrophic cardiomyopathy), and MTHFS (25%; major depression, schizophrenia, bipolar disorder). Other notable genes with new high-confidence isoforms include CPLX2 (10%; schizophrenia, epilepsy) and MAOB (9%; targeted for Parkinson's disease treatment). We identified 1,917 medically relevant genes expressing multiple isoforms in human frontal cortex, where 1,018 had multiple isoforms with different protein coding sequences, demonstrating the need to better understand how individual isoforms from a single gene body are involved in human health and disease, if at all. Exactly 98 of the 1,917 genes are implicated in brain-related diseases, including Alzheimer's disease genes such as APP (Aß precursor protein; five), MAPT (tau protein; four), and BIN1 (eight). As proof of concept, we also found 99 differentially expressed RNA isoforms between Alzheimer's cases and controls, despite the genes themselves not exhibiting differential expression. Our findings highlight the significant knowledge gaps in RNA isoform diversity and their medical relevance. Deep long-read RNA sequencing will be necessary going forward to fully comprehend the medical relevance of individual isoforms for a "single" gene.

Voice Therapy According to the Rehabilitation Treatment Specification System: Expert Consensus Ingredients and Targets.

Purpose Clinical trials have demonstrated that standardized voice treatment programs are effective for some patients, but identifying the unique individual treatment ingredients specifically responsible for observed improvements remains elusive. To address this problem, the authors used a taxonomy of voice therapy, the Rehabilitation Treatment Specification System (RTSS), and a Delphi process to develop the RTSS-Voice (expert consensus categories of measurable and unique voice treatment ingredients and targets). Method Initial targets and ingredients were derived from a taxonomy of voice therapy. Through six Delphi Rounds, 10 vocal rehabilitation experts rated the measurability and uniqueness of individual treatment targets and ingredients. After each round, revisions (guided by the experts' feedback) were finalized among a primary reader (a voice therapy expert) and two external readers (rehabilitation experts outside the field of voice). Consensus was established when the label and definition of an ingredient or target reached a supramajority threshold (≥ 8 of 10 expert agreement). Results Thirty-five target and 19 ingredient categories were agreed to be measurable, unique, and accurate reflections of the rules and terminology of the RTSS. Operational definitions for each category included differences in the way ingredients are delivered and the way individual targets are modified by those ingredients. Conclusions The consensus labels and operationalized ingredients and targets making up the RTSS-Voice have potential to improve voice therapy research, practice, and education/training. The methods used to develop these lists may be useful for other speech, language, and hearing treatment specifications. Supplemental Material https://doi.org/10.23641/asha.15243357.

Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas' disease.

Chagas' disease, caused by infection with the parasite Trypanosoma cruzi, is the major cause of heart failure in Latin America. Classic clinical manifestations result from the infection of heart muscle cells leading to progressive cardiomyopathy. To ameliorate disease, chemotherapy must eradicate the parasite. Current drugs are ineffective and toxic, and new therapy is a critical need. To expedite drug screening for this neglected disease, we have developed and validated a cell-based, high-throughput assay that can be used with a variety of untransfected T. cruzi isolates and host cells and that simultaneously measures efficacy against the intracellular amastigote stage and toxicity to host cells. T. cruzi-infected muscle cells were incubated in 96-well plates with test compounds. Assay plates were automatically imaged and analyzed based on size differences between the DAPI (4',6-diamidino-2-phenylindole)-stained host cell nuclei and parasite kinetoplasts. A reduction in the ratio of T. cruzi per host cell provided a quantitative measure of parasite growth inhibition, while a decrease in count of the host nuclei indicated compound toxicity. The assay was used to screen a library of clinically approved drugs and identified 55 compounds with activity against T. cruzi. The flexible assay design allows the use of various parasite strains, including clinical isolates with different biological characteristics (e.g., tissue tropism and drug sensitivity), and a broad range of host cells and may even be adapted to screen for inhibitors against other intracellular pathogens. This high-throughput assay will have an important impact in antiparasitic drug discovery.

A nonazole CYP51 inhibitor cures Chagas' disease in a mouse model of acute infection.

Chagas' disease, the leading cause of heart failure in Latin America, is caused by the kinetoplastid protozoan Trypanosoma cruzi. The sterols of T. cruzi resemble those of fungi, both in composition and in biosynthesis. Azole inhibitors of sterol 14alpha-demethylase (CYP51) successfully treat fungal infections in humans, and efforts to adapt the success of antifungal azoles posaconazole and ravuconazole as second-use agents for Chagas' disease are under way. However, to address concerns about the use of azoles for Chagas' disease, including drug resistance and cost, the rational design of nonazole CYP51 inhibitors can provide promising alternative drug chemotypes. We report the curative effect of the nonazole CYP51 inhibitor LP10 in an acute mouse model of T. cruzi infection. Mice treated with an oral dose of 40 mg LP10/kg of body weight twice a day (BID) for 30 days, initiated 24 h postinfection, showed no signs of acute disease and had histologically normal tissues after 6 months. A very stringent test of cure showed that 4/5 mice had negative PCR results for T. cruzi, and parasites were amplified by hemoculture in only two treated mice. These results compare favorably with those reported for posaconazole. Electron microscopy and gas chromatography-mass spectrometry (GC-MS) analysis of sterol composition confirmed that treatment with LP10 blocked the 14alpha-demethylation step and induced breakdown of parasite cell membranes, culminating in severe ultrastructural and morphological alterations and death of the clinically relevant amastigote stage of the parasite.

Changing stigmatizing perceptions and recollections about mental illness: the effects of NAMI's in Our Own Voice.

In Our Own Voice (IOOV) is a 90-min anti-stigma program that comprises face-to-face stories of challenges of mental illness and hopes and dreams commensurate with recovery. We pared down IOOV to a 30-min version, using information from two focus groups. In this study, effects of 90- versus 30-min IOOV are contrasted with 30 min of education. Two hundred research participants were randomly assigned to one of these three conditions and completed a measure of stigmatizing perceptions and recollections. People in the education group remembered more negatives than the two IOOV groups. To control for overall response rate, a difference ratio was determined (difference in positive and negative recollection divided by overall recollections). Results showed the two IOOV conditions had significantly better ratios than education. These findings suggest the 30 min version of IOOV is as effective as the 90 min standard.

Identification of a new class of nonpeptidic inhibitors of cruzain.

Cruzain is the major cysteine protease of Trypanosoma cruzi, which is the causative agent of Chagas disease and is a promising target for the development of new chemotherapy. With the goal of developing potent nonpeptidic inhibitors of cruzain, the substrate activity screening (SAS) method was used to screen a library of protease substrates initially designed to target the homologous human protease cathepsin S. Structure-based design was next used to further improve substrate cleavage efficiency by introducing additional binding interactions in the S3 pocket of cruzain. The optimized substrates were then converted to inhibitors by the introduction of cysteine protease mechanism-based pharmacophores. Inhibitor 38 was determined to be reversible even though it incorporated the vinyl sulfone pharmacophore that is well documented to give irreversible cruzain inhibition for peptidic inhibitors. The previously unexplored beta-chloro vinyl sulfone pharmacophore provided mechanistic insight that led to the development of potent irreversible acyl- and aryl-oxymethyl ketone cruzain inhibitors. For these inhibitors, potency did not solely depend on leaving group p K a, with 2,3,5,6-tetrafluorophenoxymethyl ketone 54 identified as one of the most potent inhibitors with a second-order inactivation constant of 147,000 s (-1) M (-1). This inhibitor completely eradicated the T. cruzi parasite from mammalian cell cultures and consequently has the potential to lead to new chemotherapeutics for Chagas disease.

Development of protease inhibitors for protozoan infections.

PURPOSE OF REVIEW: To highlight the promise of parasite proteases as targets for development of new antiparasitic chemotherapy. Proteolytic enzymes play key roles in the life cycle of protozoan parasites or the pathogenesis of diseases they produce. These roles include processing of host or parasite surface proteins for invasion of host cells, digestion of host proteins for nutrition, and inactivation of host immune defense mediators. RECENT FINDINGS: Drug development for other markets has shown that proteases are druggable targets, and protease inhibitors are now licensed or in clinical development to treat hypertension, diabetes, thrombosis, osteoporosis, infectious diseases, and cancer. Several protease targets have been validated by genetic or chemical knockout in protozoan parasites. Many other parasite proteases appear promising as targets, but require more work for validation, or to identify viable drug leads. Because homologous proteases function as key enzymes in several parasites, targeting these proteases may allow development of a single compound, or a set of similar compounds, that target multiple diseases including malaria, trypanosomiasis, leishmaniasis, toxoplasmosis, cryptosporidiosis, and amebiasis. SUMMARY: Proteases have been validated as targets in a number of parasitic infections. Proteases are druggable targets as evidenced by effective antiprotease drugs for the treatment of many human diseases including hypertension and AIDS. Future drug development targeting parasite proteases will be aided by the strong foundation of biochemical, structural, and computational databases already published or available online.

Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes.

A systematic study of P2 and P3 substitution in a series of vinyl sulfone cysteine protease inhibitors is described. The introduction of a methyl substituent in the P2 phenylalanine aryl ring had a favorable effect on protease inhibition and conferred modest selectivity for rhodesain over cruzain. Rhodesain selectivity could be enhanced further by combining these P2 modifications with certain P3 amide substituents.

Usage of an Electronic Database and Checklist System for Improvement in Magnetic Resonance Imaging Acquisition.

PURPOSE: To determine whether implementation of an easily accessible electronic database promotes significant reporting of magnetic resonance imaging (MRI) acquisition errors. Additionally, we wanted to see if analysis of the error reports could be used to create a comprehensive checklist to avoid the most common errors. METHODS: A new, simple, and efficient electronic database reporting system was written in-house and implemented at our institution. Over the course of 4 months, the use of this database enabled collection and analysis of sufficient data for trend analysis. A simple 4-point checklist for MRI technologist use was developed based on the most commonly reported errors. Reported MRI acquisition error rates were collected and analyzed thereafter. RESULTS: By the first full month of implementation, MRI scan error reporting increased from a previous negligible baseline rate to 3.03%. The comprehensive checklist was based on the 4 most common issues reported. Verification of checklist use showed that adherence to this requirement averaged greater than 94%. Immediately following roll out of the checklist, the percentage of errors reported fell to 1.7% with a continued decline in error reports thereafter. An approximately 60% reduction in errors in the last month of the study was evident as compared to the first month of data collection. CONCLUSIONS: The use of an efficient error reporting system and implementation of a checklist based on the most common MRI acquisition errors results in a substantial decrease in the baseline MRI acquisition error rates.

Respirable dust exposure and respiratory health in male Taiwanese steelworkers.

The objective of this cross-sectional study was to investigate the prevalence and determinants of respiratory symptoms and lung function and their association with occupational dust exposure in Taiwanese steelworkers. The study was conducted on an integrated-steel company in Taiwan from March 1989 to February 1990. After excluding workers in the coke ovens and ex-smokers, we performed physical examinations on 1,339 male workers in the iron making and steel making factories. Subjects were interviewed regarding respiratory symptoms using a Chinese version of the American Thoracic Society respiratory questionnaire and were examined with respect to their lung function using spirometry. Objective dust exposure was measured using personal air sampling with 277 valid samples. Prevalences of cough frequently, chronic cough, phlegm frequently, chronic phlegm, wheezing occasionally, and breathlessness were 11.4%, 9.3%, 14.6%, 11.9%, 2.6%, and 6.5%, respectively. Duration of employment, smoking, subjective dustiness, and past respiratory illnesses can predict these respiratory symptoms. Average respirable dust exposure significantly decreased the forced vital capacity (FVC) and forced expiratory volume in one second (FEVI.0) in smoking workers. In the non-smokers, an effect of respirable dust exposure on FEVl.0/FVC was shown. Since the main ingredients of dust in such a steelworks usually contained mixtures of oxides and silicates other than silica dust, respirable dust exposure in steelworks might impair lung function, especially among smokers.

Idiopathic slipped capital femoral epiphysis in Amish children.

BACKGROUND: Of the many studies of slipped capital femoral epiphysis, none have specifically addressed Amish children. The Amish reflect a small gene pool relative to the general white North American population. Additional knowledge of the demographics of this disorder in Amish children may provide genetic insights. The purpose of this study was to review the demographics of slipped capital femoral epiphysis in the Amish population. METHODS: A retrospective review of the cases of twenty-five Amish children with slipped capital femoral epiphysis treated at two institutions was performed. The child's gender, age, weight, height, and body mass index at the time of the diagnosis; duration of symptoms; laterality of the slip; birth weight; family history; and slip severity were recorded. The slip was classified as stable or unstable. Patients who had been included in a previously published multicenter study served as a control group. RESULTS: There were seventeen boys and eight girls with a total of thirty-three slipped capital femoral epiphyses; eight of the slips were bilateral. At the time of the diagnosis, the mean age (and standard deviation) was 13.4 +/- 1.6 years, the mean weight and height were 55.6 +/-12.4 kg and 155.5 +/- 10.2 cm, and the mean body mass index was 23.4 +/- 5.4 kg/m(2). The mean duration of symptoms was 6.6 +/-9.0 months. There were thirty-one stable and two unstable slips with a mean slip angle of 38 degrees +/- 20 degrees . Nine (39%) of twenty-three children for whom the information had been recorded had a positive family history of slipped capital femoral epiphysis, a rate that is higher than the 9% and 14.5% rates reported in two other series (p = 0.002). The Amish children were not as heavy as their non-Amish counterparts (55.6 +/- 12.4 kg compared with 66.4 +/- 17.7 kg, p = 0.0036). CONCLUSIONS: Although the children in this study were moderately heavy, they could not be classified as obese on the basis of weight-for-age or body-mass-index percentiles. The high prevalence of family members with slipped capital femoral epiphysis may reflect either a genetic or environmental component, or an interaction between genetics and environment (for example, work load or common chores requiring particular physical positions) in the Amish population.

Self-reported patient safety competence among Canadian medical students and postgraduate trainees: a cross-sectional survey.

BACKGROUND: Quality and patient safety (PS) are critical components of medical education. This study reports on the self-reported PS competence of medical students and postgraduate trainees. METHODS: The Health Professional Education in Patient Safety Survey was administered to medical students and postgraduate trainees in January 2012. PS dimension scores were compared across learning settings (classroom and clinical) and year in programme. RESULTS: Sixty-three percent (255/406) of medical students and 32% (141/436) of postgraduate trainees responded. In general, both groups were most confident in their learning of clinical safety skills (eg, hand hygiene) and least confident in learning about sociocultural aspects of safety (eg, understanding human factors). Medical students' confidence in most aspects of safety improved with years of training. For some of the more intangible dimensions (teamwork and culture), medical students in their final year had lower scores than students in earlier years. Thirty-eight percent of medical students felt they could approach someone engaging in unsafe practice, and the majority of medical students (85%) and postgraduate trainees (78%) agreed it was difficult to question authority. CONCLUSIONS: Our results suggest the need to improve the overall content, structure and integration of PS concepts in both classroom and clinical learning environments. Decreased confidence in sociocultural aspects of PS among medical students in the final year of training may indicate that culture in clinical settings negatively affects students' perceived PS competence. Alternatively, as medical students spend more time in the clinical setting, they may develop a clearer sense of what they do not know.