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INTRODUCTION/AIMS: Rhabdomyolysis is an etiologically heterogeneous, acute necrosis of myofibers characterized by transient marked creatine kinase (CK) elevation associated with myalgia, muscle edema, and/or weakness. The study aimed to determine the role of electrodiagnostic (EDX) testing relative to genetic testing and muscle biopsy in patients with unprovoked rhabdomyolysis in identifying an underlying myopathy. METHODS: EDX database was reviewed to identify unprovoked rhabdomyolysis patients who underwent EDX testing between January 2012 and January 2022. Each patient's clinical profile, EDX findings, muscle pathology, laboratory, and genetic testing results were analyzed. RESULTS: Of 66 patients identified, 32 had myopathic electromyography (EMG). Muscle biopsy and genetic testing were performed in 41 and 37 patients, respectively. A definitive diagnosis was achieved in 15 patients (11 myopathic EMG and 4 nonmyopathic EMG; p = .04) based on abnormal muscle biopsy (4/11 patients) or genetic testing (12/12 patients, encompassing 5 patients with normal muscle biopsy and 3 patients with nonmyopathic EMG). These included seven metabolic and eight nonmetabolic myopathies (five muscular dystrophies and three ryanodine receptor 1 [RYR1]-myopathies). Patients were more likely to have baseline weakness (p < .01), elevated baseline CK (p < .01), and nonmetabolic myopathies (p = .03) when myopathic EMG was identified. DISCUSSION: Myopathic EMG occurred in approximately half of patients with unprovoked rhabdomyolysis, more likely in patients with weakness and elevated CK at baseline. Although patients with myopathic EMG were more likely to have nonmetabolic myopathies, nonmyopathic EMG did not exclude myopathy, and genetic testing was primarily helpful to identify an underlying myopathy. Genetic testing should likely be first-tier diagnostic testing following unprovoked rhabdomyolysis.
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Eletromiografia , Rabdomiólise , Humanos , Rabdomiólise/diagnóstico , Rabdomiólise/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Músculo Esquelético/patologia , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Testes Genéticos/métodos , Eletrodiagnóstico/métodos , Adulto Jovem , Creatina Quinase/sangue , Biópsia , Estudos Retrospectivos , AdolescenteRESUMO
PURPOSE OF REVIEW: This review provides an overview of the management and treatment landscape of inclusion body myositis (IBM), while highlighting the current challenges and future directions. RECENT FINDINGS: IBM is a slowly progressive myopathy that predominantly affects patients over the age of 40, leading to increased morbidity and mortality. Unfortunately, a definitive cure for IBM remains elusive. Various clinical trials targeting inflammatory and some of the noninflammatory pathways have failed. The search for effective disease-modifying treatments faces numerous hurdles including variability in presentation, diagnostic challenges, poor understanding of pathogenesis, scarcity of disease models, a lack of validated outcome measures, and challenges related to clinical trial design. Close monitoring of swallowing and respiratory function, adapting an exercise routine, and addressing mobility issues are the mainstay of management at this time. SUMMARY: Addressing the obstacles encountered by patients with IBM and the medical community presents a multitude of challenges. Effectively surmounting these hurdles requires embracing cutting-edge research strategies aimed at enhancing the management and treatment of IBM, while elevating the quality of life for those affected.
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Miosite de Corpos de Inclusão , Miosite , Humanos , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/terapia , Miosite de Corpos de Inclusão/patologia , Qualidade de Vida , Miosite/diagnósticoRESUMO
OBJECTIVES: Symptomatic myopathy in sarcoidosis patients is not always due to sarcoid myopathy (ScM). We investigated the clinical and pathological spectrum including myxovirus resistance protein A (MxA) expression among sarcoidosis patients. METHODS: We reviewed the Mayo Clinic database (May 1980-December 2020) to identify sarcoidosis patients with myopathic symptoms and pathological evidence of myopathy. RESULTS: Among 5885 sarcoidosis patients, 21 had symptomatic myopathy. Eight carried a diagnosis of sarcoidosis 5.5 years (median) prior to myopathy onset. Eleven patients had ScM. The remaining had non-sarcoid myopathies (five IBM, one immune-mediated necrotizing myopathy, one non-specific myositis, two non-specific myopathy and one steroid myopathy). Estimated frequency of IBM is 85 per 100 000 sarcoidosis patients. The following features were associated with non-sarcoid myopathies (P < 0.05): (i) predominant finger flexor and quadriceps weakness, (ii) modified Rankin scale (mRS) >2 at time of diagnosis, (iii) creatine kinase >500 U/l, and (iv) absence of intramuscular granulomas. Sarcoplasmic MxA expression was observed in scattered myofibres in three patients, two of whom were tested for DM-specific autoantibodies and were negative. Immunosuppressive therapy led to improvement in mRS ≥1 in 5/10 ScM, none of the five IBM, and 3/3 remaining patients with non-sarcoid myopathies. DISCUSSION: Symptomatic myopathy occurred in 0.36% of sarcoidosis. IBM was the second most common cause of myopathies after ScM. Frequency of IBM in sarcoidosis is higher than in the general population. Recognition of features suggestive of alternative aetiologies can guide proper treatment. Our findings of abnormal MxA expression warrant a larger study.
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Doenças Autoimunes , Doenças Musculares , Miosite , Sarcoidose , Humanos , Miosite/patologia , Sarcoidose/diagnóstico , Granuloma/patologiaRESUMO
INTRODUCTION/AIMS: Complex repetitive discharges (CRDs) are spontaneous electromyography (EMG) waveforms often associated with chronic neurogenic or myopathic diseases, but incidentally identified CRDs have also been described. In this study we describe the distribution and possible significance of incidentally seen CRDs in otherwise normal electrodiagnostic studies. METHODS: A retrospective chart review was performed of all patients with CRDs incidentally documented on otherwise normal electrodiagnostic studies at Mayo Clinic from January 2013 through December 2020. Each patient's clinical symptoms, referral reason, electrodiagnostic report, and imaging studies were analyzed using descriptive statistics. RESULTS: Ninety-four patients (86 females; mean age, 62 years; range, 20 to 86 years) and 107 CRDs were studied. The most common neuromuscular reasons for electrodiagnostic referrals included radiculopathy, peripheral neuropathy, and myopathy. Mean symptom duration was 43 months (range, 1 to 312 months). Eighty-five patients had a CRD identified in one muscle (range, in all patients, one to five muscles). CRDs were identified most frequently in tensor fasciae latae (n = 21), biceps brachii (n = 16), and gluteus maximus (n = 9). Of the 58 patients in whom imaging was available, 46 (79%) had abnormalities that corresponded to the myotome in which the CRDs were visualized, most commonly L5 (n = 19) and C6 (n = 12). Of these 46 patients, 28 (61%) were referred for radicular or limb pain. DISCUSSION: CRDs can be incidentally noted on otherwise normal electrodiagnostic studies, most commonly in L5 and C6 myotomes. The mechanism of CRDs in the absence of electrodiagnostic features of axon loss or remodeling is unknown.
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Eletromiografia , Radiculopatia , Feminino , Humanos , Pessoa de Meia-Idade , Eletromiografia/métodos , Músculo Esquelético/diagnóstico por imagem , Radiculopatia/diagnóstico , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the peripheral nervous system presenting as the initial manifestation of a lymphoma (primary NL [PNL]) or in relapse of a known lymphoma (secondary NL [SNL]). This report details and compares the neurologic clinicopathologic characteristics of these 2 groups. METHODS: This retrospective study was performed on patients diagnosed with pathologically confirmed NL in nerve between January 1, 1992, and June 31, 2020. Patient clinical characteristics, neurologic examination, imaging studies, EMG, and nerve biopsy data were collected, analyzed, and compared between PNL and SNL. RESULTS: A total of 58 patients were identified (34 PNL and 24 SNL). Time from neurologic symptom onset to diagnosis was longer in PNL at 18.5 months compared with 5.5 months in SNL (p = 0.01). Neurologic symptoms were similar in both patient groups and included primarily sensory loss (98%), severe pain (76%), and asymmetric weakness (76%). A wide spectrum of EMG-confirmed different neuropathy patterns were observed, but patients with SNL had increased numbers of mononeuropathies (n = 8) compared with PNL (n = 1, p = 0.01). MRI studies detected NL more frequently (86%) compared with fluorodeoxyglucose (FDG)-PET CT imaging studies (60%) (p = 0.007). Nerve biopsies revealed B-cell lymphoma (PNL n = 32, SNL n = 22), followed by T-cell lymphoma (PNL n = 2, SNL n = 2), with increased demyelination in both groups and increased axonal degeneration (p = 0.01) and multifocal myelinated fiber loss (p = 0.04) significant in SNL vs PNL. Identifying SNL resulted in patient treatment modifications but a worse prognosis compared with PNL (p = 0.025). DISCUSSION: While PNL and SNL are both primarily painful and asymmetric neuropathies with axonal and demyelinating features on EMG and nerve biopsy, SNL presents somewhat differently than PNL with fulminant, asymmetric often mononeuropathies better detected on MRI than FDG-PET/CT. The focal pattern of SNL is likely a result of residual cancer cells that evaded initial chemotherapy, which does not cross the blood-nerve barrier, and these cells can later recur and result in fulminant disease. Although still resulting in a poorer prognosis, identifying SNL is important because this changed treatment and management in every SNL case.
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Eletromiografia , Neurolinfomatose , Humanos , Masculino , Neurolinfomatose/diagnóstico por imagem , Neurolinfomatose/patologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: Complex repetitive discharges (CRDs) are incompletely understood needle electromyography (EMG) waveforms seen in both myopathic and neurogenic disorders including radiculopathies. This study aimed to clarify the significance of CRDs in patients with radiculopathies. METHODS: This case-control study randomly identified 100 patients with needle EMG evidence of radiculopathy demonstrating at least one CRD in the electrodiagnostically involved myotome between January 2017 and January 2022. These patients were compared with 100 randomly selected patients with EMG evidence of radiculopathy without CRDs controlled for sex, age at EMG testing, and affected nerve root segment. Patient clinical symptoms, neurologic examination, EMG features, and imaging were analyzed. A paired sample t-test for categorial data and χ2 test for nonparametric data were used for statistical analysis with significance defined as P < 0.05. RESULTS: Patients with radiculopathies with CRDs had longer disease duration averaging 59 months (range 1-480) compared with patients with radiculopathies without CRDs averaging 26 months (range 1-192, P < 0.01). Clinical symptoms of paresthesias and weakness were both significantly more common in patients with radiculopathies with CRDs than those without CRDs (P < 0.01 and 0.01, respectively). Needle EMG demonstrated a greater average number of muscles with neurogenic motor unit potentials per radiculopathy in patients with radiculopathies with CRDs compared with those without CRDs. Imaging studies of patients with radiculopathies with CRDs were more likely to reveal evidence of nerve root compression (P < 0.01). CONCLUSIONS: The presence of CRDs in patients with radiculopathies is consistent with clinically more symptomatic radiculopathies and a longer duration of nerve root compromise.
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Objective: To reduce unwitnessed inpatient falls on the neurology services floor at an academic medical center by 20% over 15 months. Patients and Methods: A 9-item preintervention survey was administered to neurology nurses, resident physicians, and support staff. Based on survey data, interventions targeting fall prevention were implemented. Providers were educated during monthly in-person training sessions regarding the use of patient bed/chair alarms. Safety checklists were posted inside each patient's room reminding staff to ensure that bed/chair alarms were on, call lights and personal items were within reach, and patients' restroom needs were addressed. Preimplementation (January 1, 2020, to March 31, 2021) and postimplementation (April 1, 2021, to June 31, 2022) rates of falls in the neurology inpatient unit were recorded. Adult patients hospitalized in 4 other medical inpatient units not receiving the intervention served as a control group. Results: Rates of falls, unwitnessed falls, and falls with injury all decreased after intervention in the neurology unit, with rates of unwitnessed falls decreasing by 44% (2.74 unwitnessed falls per 1000 patient-days before intervention to 1.53 unwitnessed falls per 1000 patient-days after intervention; P=.04). Preintervention survey data revealed a need for education and reminders on inpatient fall prevention best practices given a lack of knowledge on how to operate fall prevention devices, driving the implemented intervention. All staff reported significant improvement in operating patient bed/chair alarms after intervention (P<.001). Conclusion: A collaborative, multidisciplinary approach focusing on provider fall prevention education and staff checklists is a potential technique to reduce neurology inpatient fall rates.
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OBJECTIVES: The objective of this study was to study early-onset radiation-induced neuropathy reviewing neurologic course, steroid response, and available nerve biopsies. METHODS: Patients coded with radiation-induced neuropathy within 6 months of radiation were reviewed from January 1,1999, to August 31, 2022. Patients had to have electrodiagnostically confirmed neuropathy localized within or distal to radiation fields. Neurologic course and nerve biopsies were reviewed. RESULTS: Twenty-eight patients (16 male and 12 female patients, mean age 63.8 years) were identified. The average radiation dose was 4,659 cGy (range 1,000-7,208). Tumor infiltration was not observed on MRI and PET. Postradiation onsets averaged 2 months (range 0-5). Localizations included brachial (n = 4) plexopathies, lumbosacral (n = 12) plexopathies, radiculopathies (n = 10), and mononeuropathies (n = 2). Neuropathic pain (n = 25) and weakness (n = 25) were typical. The clinical courses were subacute monophasic (n = 14), chronic progressive (n = 8), or static (n = 1), and 5 were without follow-up. Nerve biopsies (n = 8) showed an inflammatory ischemic process with perivascular inflammatory infiltrates (n = 7) or microvasculitis (n = 2). Nine patients, 7 with monophasic courses, received steroid burst therapy with symptom improvement in 8. No patients recovered entirely back to baseline. DISCUSSION: In contrast to chronic radiation-induced neuropathy, early-onset patients most commonly have painful monophasic courses with residual deficits, possibly steroid responsive. An ischemic inflammatory pathogenesis is suggested.
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Neuralgia , Radiculopatia , Vasculite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biópsia , Neuralgia/etiologia , EsteroidesRESUMO
Background and Objectives: Muscle-specific kinase (MuSK) antibody-positive myasthenia gravis (MuSK + MG) is a form of MG with bulbar-predominant symptoms often resistant to conventional treatments. Patients with MuSK + MG may have an electrodiagnostic (EDX) profile distinct from other MG. This study compares EDX features of MuSK + MG with acetylcholine receptor (AChR) antibody-positive MG (AChR + MG) to discern whether any unique EDX pattern exists that can aid in clinical diagnosis. Methods: From January 1, 2010, through December 31, 2020, all patients with MuSK + MG at our institution were identified and randomly matched to an AChR + MG cohort in a 1:2 ratio based on sex, age at onset, and subsequently Myasthenia Gravis Foundation of America (MGFA) clinical severity for a case-control study. Each patient's clinical profile, treatment, and EDX testing were summarized and analyzed. Results: Twenty-two patients with MuSK + MG (18 female) and 44 patients with AChR + MG were studied. The average symptom duration at presentation was shorter in the MuSK + MG group (4.7 years) compared with AChR + MG (10.9 years). Myotonic discharges were rare in both groups but more frequently observed in patients with MuSK + MG (10%) identified in 5 muscles in 2 patients compared with AChR + MG (2%) noted in only 1 muscle in 1 patient. Patients with MuSK + MG more often had myopathic appearing motor unit potentials (MUPs) (41% vs 30%) compared with AChR + MG. Myopathic appearing MUPs were found in milder cases of MuSK + MG (MGFA class I-IIB) compared with AChR + MG (MGFA Class IIB-V). Discussion: Patients with MuSK + MG may have a recognizable EDX profile from AchR + MG that includes (1) myotonic discharges, (2) greater occurrence of myopathic appearing MUPs in clinically mild disease, and (3) symptoms leading to earlier testing.
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ABSTRACT: The Obesity Paradox describes the counterintuitive finding that although obesity contributes to the development of chronic conditions such as chronic kidney disease and cardiovascular disease, obesity seems to improve mortality in patients with these diseases. This paradox has also been sited in the critical care literature in regard to acute kidney injury, obesity and mortality. This study's objective is to examine the impact of obesity and post-surgical acute kidney injury on hospital length of stay and 2-year mortality after orthopedic surgery.We reviewed the electronic medical records of all adult elective orthopedic surgery patients over 2âyears in a large academic hospital. The 1783 patients who met inclusion criteria were divided into obese (body mass index, BMIâ≥â30, nâ=â1123) and non-obese groups (BMI <30, nâ=â660). Demographics, medications, comorbidities, and perioperative variables were included in multivariable logistic regression analyses with acute kidney injury, length of hospital stay, and two-year mortality as primary outcomes. Outcomes were analyzed for the entire group, the obese cohort and the non-obese cohort.Acute kidney injury developed in 5% of the post-surgical orthopedic patients. Obesity increased the likelihood of developing acute kidney injury post orthopedic surgery (odds ratio [OR]â=â1.82; 95% Confidence interval [CI] 1.05-3.15, Pâ=â.034). Acute kidney injury increased length of stay by 1.3âdays and increased the odds of two-year mortality (ORâ=â2.08; 95% CI 1.03-4.22, Pâ=â.041). However, obese patients had a decreased likelihood of two-year mortality (ORâ=â0.53; 95% CI 0.33-0.84, Pâ=â.009).In adult orthopedic surgery patients, obesity increased the risk of acute kidney injury. Patients who developed an acute kidney injury had longer hospital stays and higher two-year mortality. Paradoxically, obesity decreased two-year mortality.
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Injúria Renal Aguda/etiologia , Obesidade/complicações , Procedimentos Ortopédicos , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/mortalidade , Idoso , Estudos de Coortes , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Fatores de RiscoRESUMO
OBJECTIVE: Hemifacial atrophy (HFA) is a rare disorder characterized by progressive unilateral wasting facial soft tissue, muscle, and/or bone. Trigeminal nerve abnormalities may contribute to or result from disease pathophysiology. We aimed to gain further insights into the role of trigeminal pathophysiology along the HFA severity spectrum. METHODS: A systematic literature review was performed according to PRISMA standards. Retrospective cases of HFA from the literature and Mayo Clinic EMG database were pooled for descriptive and semi-quantitative analysis. RESULTS: Overall, 13 total HFA patients were identified through literature and database reviews. Trigeminal nerve testing was abnormal in 9/13 (69%), exclusively in moderate-severe cases. Abnormalities suggested a peripheral (7/9, 78%) or mixed central/peripheral (2/9, 22%) localization. Trigeminal nerve abnormalities were not identified in any of the 4 cases with mild disease severity. CONCLUSION: Moderate to severe cases of HFA were associated with electrophysiological trigeminal abnormalities. No abnormalities were seen in mild cases of HFA. SIGNIFICANCE: Trigeminal nerve electrophysiology may serve as a biomarker of moderate-severe disease progression, likely reflecting the consequences of progressive soft tissue atrophy.
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Hospital readmission rates are used as a metric to measure quality patient care. While several tools predict readmissions based on patient-specific characteristics, this study assesses if physician characteristics correlate with hospital readmission rates.In a 5-year retrospective electronic record review at a single institution, 31 internal medicine attending physicians' discharges were tracked for a total of 70 physician years, and 15,933 hospital discharges. Each physician's yearly 7-day, 8 to 30-day, and 30-day readmission rates were compared. Each rate was also correlated with years of post-graduate clinical experience, discharge volume, physician sex, and fiscal year.Individual physicians had significantly different 7-day, 8 to 30-day, and 30-day readmission rates from each other. The rates were not related to sex, years after post-graduate training, or fiscal year. However, physician patient volume correlated with 7-day readmission rates. Physicians who discharged ≤100 patients per year had a higher 7-day readmission rate than physicians who discharged >100 patients per year. This correlation with patient volume did not hold for the 8 to 30-day and 30-day readmission rates.Individual physicians differ in their patient readmission rates in 7-day, 8 to 30-day, and 30-day categories. A critical level of a physician's hospital activity, as reflected by the number of patient discharges per year (>100), results in lower 7-day readmission rates. Sex, post-graduate years of clinical experience, and fiscal year did not play a role. The lack of correlation between each physicians' 7-day and 8 to 30-day readmission rates suggests that different physician factors are involved in these 2 rates.
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Readmissão do Paciente/estatística & dados numéricos , Padrões de Prática Médica/normas , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Adulto , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/normas , Alta do Paciente/estatística & dados numéricos , Pennsylvania , Padrões de Prática Médica/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Experiential vertical integration of basic science with clinical concepts remains a challenge in medical school curricula. In addition, training physicians in nutritional competency that translates into patient care is a challenging endeavor ranging from biochemical mechanisms to socioeconomic challenges. METHODS: Employing a social constructivism paradigm, we implemented a collaborative cook-off competition in a basic science course where 140 first-year medical students per year translated their studies of inborn errors of metabolism, energy metabolism, micronutrients and immunology into edible creations intended for people with disorders requiring dietary management. After learning about the disorders in lecture, problem-based learning, team-based learning and through patient interviews, four problem-based learning groups (7 students per group) were assigned to prepare food dishes for one of the five assigned disorders. Together, students researched the dietary requirements, shopped, paid for, prepared, presented and shared their food. To the class, faculty and re-invited patients, the groups explained the dietary restrictions, the chosen ingredients, how they prepared the food, and why their dish was suitable for the disorder. Each category was judged and awarded a first-place food prize with a grand prize at the end. At the completion of the course, student feedback was elicited via anonymous evaluations. Over 3 years, 380 comments were collected. We used grounded theory to generate a codebook that was then analyzed by the authors for overarching themes. RESULTS: Qualitative results described three major themes: increased relevance of basic science to real life, increased empathy towards complying with dietary restrictions, and increased student group cohesiveness. CONCLUSION: The patient-centered cook-off competition taught students the relevance of basic science but in addition, it taught empathy towards the patient experience. We also discovered that the process of food preparation was a bonding experience that promoted collaboration, cohesiveness and friendship within the student class.
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How medical inter-professional (IP) education should be introduced to students is still a matter of research. We evaluated IP student attitudes before and after a busy "hands-on" clinical experience.During 3 separate trips, first/second year medical and physician assistant students and third/fourth year nursing students traveled to Central America to work together for 1 week in an underserved clinical setting. Student opinions on inter-professional education were obtained before and after Brigade-1 using the Readiness for Inter-professional Learning Scale validated questionnaire. From these results, a modified version of the survey was developed that included quantitative and qualitative responses. For brigades-2 and -3, students received this modified version of the survey pre and post brigade. Quantitative data was analyzed via paired student t test, and qualitative data was analyzed to identify emerging themes using constant comparative methodology by three separate investigators.No significant quantitative differences between IP student groups were observed in their evaluation of the importance of inter-professional education either before or after the brigades. Qualitative data noted pre-brigade expectations of positive IP, experiential and patient-centered cultural learning. Pre- and post-brigade student perspectives maintained a strong belief that high functioning IP care benefited the patient. Post-brigade perspectives revealed a shift in attitude from purely positive expectations to more practical aspects of teamwork, respect, and interpersonal relationships.Students believe that patient care benefits from IP collaboration. After a busy clinical experience requiring collaboration, students realized that functional teams require appropriate skills, roles, and respectful interpersonal relationships.
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Atitude do Pessoal de Saúde , Relações Interprofissionais , Assistentes Médicos/psicologia , Estudantes de Medicina/psicologia , Estudantes de Enfermagem/psicologia , Educação de Graduação em Medicina/métodos , Bacharelado em Enfermagem/métodos , Feminino , Humanos , Masculino , Assistência Centrada no Paciente , Assistentes Médicos/educação , Inquéritos e Questionários , Adulto JovemRESUMO
PROBLEM: Medical school curriculum continues to search for methods to develop a conceptual educational framework that promotes the storage, retrieval, transfer, and application of basic science to the human experience. To achieve this goal, we propose a metacognitive approach that integrates basic science with the humanistic and health system aspects of medical education. INTERVENTION: During the week, via problem-based learning and lectures, first-year medical students were taught the basic science underlying a disease. Each Friday, a patient with the disease spoke to the class. Students then wrote illness scripts, which required them to metacognitively reflect not only on disease pathophysiology, complications, and treatments but also on the humanistic and health system issues revealed during the patient encounter. Evaluation of the intervention was conducted by measuring results on course exams and national board exams and analyzing free responses on the illness scripts and student course feedback. The course exams and National Board of Medical Examiners questions were divided into 3 categories: content covered in lecture, problem-based learning, or patient + illness script. Comparisons were made using Student t-test. Free responses were inductively analyzed using grounded theory methodology. CONTEXT: This curricular intervention was implemented during the first 13-week basic science course of medical school. The main objective of the course, Scientific Principles of Medicine, is to lay the scientific foundation for subsequent organ system courses. A total of 150 students were enrolled each year. We evaluated this intervention over 2 years, totaling 300 students. OUTCOME: Students scored significantly higher on illness script content compared to lecture content on the course exams (mean difference = 11.1, P = .006) and national board exams given in December (mean difference = 21.8, P = .0002) and June (mean difference = 12.7, P = .016). Themes extracted from students' free responses included the following: relevance of basic science, humanistic themes of empathy, resilience, and the doctor-patient relationship, and systems themes of cost, barriers to care, and support systems. LESSONS LEARNED: A metacognitive approach to learning through the use of patient encounters and illness script reflections creates stronger conceptual frameworks for students to integrate, store, retain, and retrieve knowledge.