RESUMO
Tacrolimus metabolism is heavily influenced by the CYP3A5 genotype, which varies widely among African Americans (AA). We aimed to assess the performance of a published genotype-informed tacrolimus dosing model in an independent set of adult AA kidney transplant (KTx) recipients. CYP3A5 genotypes were obtained for all AA KTx recipients (n = 232) from 2010 to 2019 who met inclusion criteria at a single transplant center in Philadelphia, Pennsylvania, USA. Medical record data were used to calculate predicted tacrolimus clearance using the published AA KTx dosing equation and two modified iterations. Observed and model-predicted trough levels were compared at 3 days, 3 months, and 6 months post-transplant. The mean prediction error at day 3 post-transplant was 3.05 ng/mL, indicating that the model tended to overpredict the tacrolimus trough. This bias improved over time to 1.36 and 0.78 ng/mL at 3 and 6 months post-transplant, respectively. Mean absolute prediction error-a marker of model precision-improved with time to 2.33 ng/mL at 6 months. Limiting genotype data in the model decreased bias and improved precision. The bias and precision of the published model improved over time and were comparable to studies in previous cohorts. The overprediction observed by the published model may represent overfitting to the initial cohort, possibly limiting generalizability.
Assuntos
Negro ou Afro-Americano , Citocromo P-450 CYP3A , Genótipo , Imunossupressores , Transplante de Rim , Tacrolimo , Humanos , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Negro ou Afro-Americano/genética , Masculino , Feminino , Pessoa de Meia-Idade , Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Adulto , Transplantados , Idoso , Modelos BiológicosRESUMO
INTRODUCTION: There is a critical need for comprehensive surgical training in African countries given the unmet surgical burden of disease in this region. Collaborative and progressive initiatives in global surgical education will have the greatest impact on trainees. Little is known about surgical education needs from the perspective of practicing surgeons and trainees in low-middle-income countries (LMICs). Even less is known about the potential role for simulation to augment training. METHODS: A modified Delphi methodology with 2 rounds of responses was employed to survey program directors (PD) and associate program directors (APD) of Pan-African Association of Christian Surgeons (PAACS) general surgery residency programs across eight low-middle-income countries in Africa. 3 PD/APDs and 2 surgical residents participated in semi-structured interviews centered around the role of simulation in training. Descriptive analysis was performed to elicit key themes and illustrative examples. RESULTS: The survey of program directors revealed that teaching residents the psychomotor skills need to perform intracorporeal suturing was both high priority and desired in multiple training sites. Other high priority skills were laparoscopic camera driving and medial visceral rotation. The interviews revealed a specific desire to perform laparoscopic surgery and a need for a simulation curriculum to familiarize staff and trainees with laparoscopic techniques. Several barriers to laparoscopic surgery exist, such as lack of staff familiarity with the equipment, lack of public buy in, and lack of generalizable and adaptable educational modules. Trainees saw utility in the use of simulation to optimize time in the operating room and sought opportunities to improve their laparoscopic skills. CONCLUSION: Faculty and surgical trainees in LMICs have interest in learning advanced surgical techniques, such as laparoscopy. Developing a simulation curriculum tailored to the trainees' local context has the potential to fill this need.
Assuntos
Internato e Residência , Laparoscopia , Treinamento por Simulação , Cirurgiões , Humanos , Avaliação das Necessidades , Currículo , Escolaridade , Laparoscopia/educação , Competência Clínica , Simulação por Computador , Educação de Pós-Graduação em Medicina/métodosRESUMO
African American (AA) kidney recipients have a higher risk of allograft rejection and failure compared to non-AAs, but to what extent these outcomes are due to genetic versus environmental effects is currently unknown. Herein, we tested the effects of recipient self-reported race versus genetic proportion of African ancestry (pAFR), and neighborhood socioeconomic status (SES) on kidney allograft outcomes in multiethnic kidney transplant recipients from Columbia University (N = 1083) and the University of Pennsylvania (N = 738). All participants were genotyped with SNP arrays to estimate genetic admixture proportions. US census tract variables were used to analyze the effect of neighborhood factors. In both cohorts, self-reported recipient AA race and pAFR were individually associated with increased risk of rejection and failure after adjustment for known clinical risk factors and neighborhood SES factors. Joint analysis confirmed that self-reported recipient AA race and pAFR were both associated with a higher risk of allograft rejection (AA: HR 1.61 (1.31-1.96), P = 4.05E-06; pAFR: HR 1.90 (1.46-2.48), P = 2.40E-06) and allograft failure (AA: HR 1.52 (1.18-1.97), P = .001; pAFR: HR 1.70 (1.22-2.35), P = .002). Further research is needed to disentangle the role of genetics versus environmental, social, and structural factors contributing to poor transplantation outcomes in kidney recipients of African ancestry.
Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim , Autorrelato , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Rejeição de Enxerto/genética , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/genética , Fatores de Risco , Adulto , Prognóstico , Seguimentos , População Urbana , Negro ou Afro-Americano/genética , Falência Renal Crônica/cirurgia , Falência Renal Crônica/genética , Transplantados , Etnicidade/genética , Características da Vizinhança , Taxa de Filtração Glomerular , Testes de Função Renal , Estudos de CoortesRESUMO
Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in the CYP3A5 gene and therefore retain a rapid metabolism phenotype and higher clearance of tacrolimus. Patients with this rapid metabolism typically require higher dosing to achieve therapeutic trough concentrations. This study aims to further characterize the impact of CYP3A5 genotype on clinical outcomes and financial expenditure. Methods: The CYP3A5 phenotype status was identified in 438 adult kidney transplant (KTx) recipients (96% were African American) using 3 LoF alleles (CYP3A5*3, *6 or *7). Individuals were categorized as rapid metabolism phenotype without LoF alleles' intermediate phenotype for 1 LoF allele' and slow phenotype for 2 LoF alleles. KTx outcomes (patient/kidney survival and Medicare spending) were determined using linked transplant registry and claims data. Results: Among the cohort, 23% had a rapid, 47% intermediate, and 30% a slow metabolism phenotype based on genotype. At 3 y, the rate of death censored graft failure and all cause graft failure was highest in the rapid metabolism phenotype and lowest in the intermediate metabolism phenotype group. First-year Medicare reimbursement differed significantly by genotype (rapid: $79 535, intermediate: $72 796, slow: $79 346, P = 0.03). After adjustment for donor and recipient characteristics, care for patients with intermediate metabolism was $4790 less expensive (P = 0.003). Conclusions: Pharmacogenomic assessment of African American KTx recipients may be useful to guide therapy when as CYP3A5 functional variants appear to be associated with differential outcome and spending after transplant.
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BACKGROUND: Musculoskeletal injury contributes significantly to the burden of disease in Tanzania and other LMICs. For hospitals to cope financially with this burden, they often mandate that patients pay their entire hospital bill before leaving the hospital. This creates a phenomenon of patients who remain hospitalized solely due to financial hardship. This study aims to characterize the impact of this policy on patients and hospital systems in resource-limited settings. METHODS: A mixed-methods study using retrospective medical record review and semi-structured interviews was conducted at a tertiary hospital in Moshi, Tanzania. Information regarding patient demographics, injury type, days spent in the ward after medical clearance for discharge, and hospital invoices were collected and analyzed for orthopaedic patients treated from November 2016 to June 2017. RESULTS: 346 of the 867 orthopaedic patients (39.9%) treated during this time period were found to have spent additional days in the hospital due to their inability to pay their hospital bill. Of these patients, 72 patient charts were analyzed. These 72 patients spent an average of 9 additional days in the hospital due to financial hardship (range: 1-64 days; interquartile range: 2-10.5 days). They spent an average of 112,958 Tanzanian Shillings (TSH) to pay for services received following medical clearance for discharge, representing 12.3% of the average total bill (916,840 TSH). 646 hospital bed-days were spent on these 72 patients when they no longer clinically required hospitalization. 7 (9.7%) patients eloped from the hospital without paying and 24 (33.3%) received financial assistance from the hospital's social welfare office. CONCLUSIONS: Many patients do not have the financial capacity to pay hospital fees prior to discharge. This reality has added significantly to these patients' overall financial hardship and has taken hundreds of bed-days from other critically ill patients. This single-institution, cross-sectional study provides a deeper understanding of this phenomenon and highlights the need for changes in the healthcare payment structure in Tanzania and other comparable settings.
Assuntos
Gastos em Saúde , Ortopedia , Estudos Transversais , Estresse Financeiro , Hospitalização , Humanos , Alta do Paciente , Pobreza , Estudos Retrospectivos , Tanzânia , Centros de Atenção Terciária , TireotropinaRESUMO
PURPOSE OF REVIEW: This review explores trends in the United States (US) transplant surgery workforce with a focus on historical demographics, post-fellowship job market, and quality of life reported by transplant surgeons. Ongoing efforts to improve women and racial/ethnic minority representation in transplant surgery are highlighted. Future directions to create a transplant workforce that reflects the diversity of the US population are discussed. RECENT FINDINGS: Representation of women and racial and ethnic minorities among transplant surgeons is minimal. Although recent data shows an improvement in the number of Black transplant surgeons from 2% to 5.5% and an increase in women to 12%, the White to Non-White transplant workforce ratio has increased 35% from 2000 to 2013. Transplant surgeons report an average of 4.3 call nights per week and less than five leisure days a month. Transplant ranks 1st among surgical sub-specialties in the prevalence of three well-studied facets of burnout. Concerns about lifestyle may contribute to the decreasing demand for advanced training in abdominal transplantation by US graduates. SUMMARY: Minimal improvements have been made in transplant surgery workforce diversity. Sustained and intentional recruitment and promotion efforts are needed to improve the representation of women and minority physicians and advanced practice providers in the field.
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Etnicidade , Qualidade de Vida , Feminino , Humanos , Grupos Minoritários , Estados Unidos/epidemiologia , Recursos HumanosRESUMO
BACKGROUND: Much of Sub-Saharan Africa meets the rising rates of musculoskeletal injury with traditional bone setting, especially given limitations in access to allopathic orthopaedic care. Concern for the safety of bone setter practices as well as recognition of their advantages have spurred research to understand the impact of these healers on public health. OBJECTIVES: Our study investigates the role of bone setting in Tanzania through patient utilization and perspectives. METHODS: We surveyed 212 patients at the outpatient orthopaedic clinic at Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania. Surveys were either self-administered or physician-administered. Summary statistics were calculated using XLSTAT. Open responses were analyzed using a deductive framework method. RESULTS: Of all surveys, 6.3% (n=13) reported utilizing traditional bone setting for their injury prior to presenting to KCMC. Of the self-administered surveys, 13.6% (n=6) reported utilizing bone setting compared to 4.3% (n=7) of the physician-administered surveys (p=0.050). Negative perceptions of bone setting were more common than positive perceptions and the main reason patients did not utilize bone setting was concern for competency (35.8%, n=67). CONCLUSION: Our study found lower bone setting utilization than expected considering the reliance of Tanzanians on traditional care reported in the literature. This suggests patients utilizing traditional care for musculoskeletal injury are not seeking allopathic care; therefore, collaboration with bone setters could expand allopathic access to these patients. Patients were less likely to report bone setter utilization to a physician revealing the stigma of seeking traditional care, which may present an obstacle for collaboration.
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Fraturas Ósseas/terapia , Medicinas Tradicionais Africanas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ortopedia , Pacientes Ambulatoriais , Estigma Social , Tanzânia , Adulto JovemRESUMO
Renal artery aneurysms (RAA) are rare and challenging to repair. We present a case of a 48-year-old female with solitary right kidney who had complex aneurysms near the renal hilum. CT angiogram showed fibromuscular dysplasia (FMD) features of the renal artery and 2 saccular aneurysms measuring 2.3 cm and 1 cm. An additional small lower pole renal artery added to the complexity of the case. Ex-vivo aneurysm repair was performed after the kidney was removed and flushed with preservation solution. This was followed by auto-transplantation to the right external iliac vessels. The patient did well postoperatively without need for dialysis with serum creatinine returning to normal 5 weeks after.
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Aneurisma/cirurgia , Displasia Fibromuscular/cirurgia , Transplante de Rim , Nefrectomia , Artéria Renal/cirurgia , Rim Único/complicações , Procedimentos Cirúrgicos Vasculares , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Feminino , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Rim Único/diagnóstico por imagem , Transplante Autólogo , Resultado do TratamentoAssuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Transplante de Rim , Doadores Vivos , Rim Policístico Autossômico Dominante/cirurgia , Complicações Pós-Operatórias/cirurgia , Aloenxertos , Biomarcadores , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/etiologia , Creatinina/sangue , Diagnóstico Diferencial , Feminino , Humanos , Hospedeiro Imunocomprometido , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/etiologia , Doadores Vivos/psicologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Nefrectomia/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Transplante , Revelação da VerdadeRESUMO
Background: Traditional health practitioners remain a critical source of care in Tanzania, more than 50% of Tanzanians frequently using their services. With a severe shortage of orthopaedic surgeons (1:3.3 million Tanzanians) traditional bone setters (TBSs) could potentially expand access to musculoskeletal care and improve outcomes for morbidity as a result of trauma. Objective: We sought to identify the advantages and disadvantages of traditional bone setting in Tanzania and to assess potential for collaboration between TBSs and allopathic orthopaedic surgeons. Methods: Between June and July 2017 we interviewed six TBSs identified as key informants in the regions of Kilimanjaro, Arusha, and Manyara. We conducted semi-structured interviews about practices and perspectives on allopathic healthcare, and analyzed the data using a deductive framework method. Findings: The TBSs reported that their patients were primarily recruited from their local communities via word-of-mouth communication networks. Payment methods for services included bundling costs, livestock barter, and sliding scale pricing. Potentially unsafe practices included lack of radiographic imaging to confirm reduction; cutting and puncturing of skin with unsterile tools; and rebreaking healed fractures. The TBSs described past experience collaborating with allopathic healthcare providers, referring patients to hospitals, and utilizing allopathic techniques in their practice. All expressed enthusiasm in future collaboration with allopathic hospitals. Conclusions: TBSs confer the advantages of word-of-mouth communication networks and greater financial and geographic accessibility. However, some of their practices raise concerns relating to infection, fracture malunion or nonunion, and iatrogenic trauma from manipulating previously healed fractures. A formal collaboration between TBSs and orthopaedic surgeons, based on respect and regular communication, could alleviate concerns through the development of care protocols and increase access to optimal orthopaedic care through a standardized triage and follow-up system.
Assuntos
Atitude do Pessoal de Saúde , Fixação de Fratura/métodos , Fraturas Ósseas/terapia , Fraturas Mal-Unidas/terapia , Controle de Infecções , Luxações Articulares/terapia , Medicinas Tradicionais Africanas/métodos , Idoso , Consolidação da Fratura , Fraturas não Consolidadas , Mão de Obra em Saúde , Humanos , Doença Iatrogênica , Masculino , Pessoa de Meia-Idade , Cirurgiões Ortopédicos/provisão & distribuição , Dor Processual/terapia , TanzâniaRESUMO
BACKGROUND: Patients with musculoskeletal injuries in Sub-Saharan Africa often receive prolonged inpatient treatment due to limited access to surgical care. Little is known regarding the psychosocial impact of prolonged conservative treatment for orthopaedic injuries, which may add to disability and preclude rehabilitation. METHODS: A cross-sectional, questionnaire study was conducted to characterize the psychosocial health of orthopaedic inpatients at a tertiary hospital in Moshi, Tanzania. Three validated surveys assessing coping strategies, functional social support, and symptoms of depression were orally administered to all orthopaedic patients with a length of stay (LOS)â¯≥â¯6 days by a Tanzanian orthopaedic specialist. RESULTS: Fifty-nine patient surveys were completed, and revealed 92% (54) of patients were more likely to utilize more adaptive than maladaptive coping strategies. Patients with chest or spinal column injuries were more likely to use maladaptive coping strategies (pâ¯=â¯0·027). Patients with head injuries had more social support compared to others (pâ¯=â¯0·009). Lack of insurance, limited education, and rural origins were associated with less functional social support, although this finding did not reach statistical significance. 23·7% (14) of patients had symptoms consistent with mild depression, 33·9% (20) with moderate depression, and 3·4% (2) with moderately-severe depression. LOS was the only significant predictor for depression severity. CONCLUSIONS: 61% (36) of orthopaedic inpatients exhibited depressive symptoms, indicating that the psychosocial health in this population is sub-optimal. Mental health is a crucial element of successful orthopaedic care. Access to timely surgical care would greatly decrease LOS, the most prominent predictor of depressive symptom severity.