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High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.
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Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Centrossomo/metabolismo , Cistadenocarcinoma Seroso/genéticaRESUMO
Background: Multiple myeloma (MM) accounts for 1% to 2% of all cancers. Exposure to the pesticide Agent Orange (AO) has been established as a potential risk factor for the development of monoclonal gammopathy of undetermined significance (MGUS) and, subsequently, MM in Vietnam War veterans. Methods: This study explored variation in survival related to AO exposure, transformation from MGUS to MM, and covariates. Vietnam War veterans with MM or MGUS were identified in Veterans Health Administration (VHA) health records data. Cox proportional hazards models analyzed survival as a function of AO, race, ethnicity, body mass index, nicotine dependence, alcohol use disorder, Charlson Comorbidity Index, and treatment. Autologous hematopoietic cell transplantation for MM was defined by procedure codes. Results: In the VHA 16,366 patients were identified: 11,112 patients diagnosed with MGUS and 7261 with MM during fiscal years 2010 to 2015 were identified; 12% (n = 2007) had both diagnoses. No statistically significant difference in the rate of transformation from MGUS to MM in the AO exposed and AO not exposed groups was found. In survival models, AO exposure was associated with slightly lower mortality. Alcohol use disorder, nicotine dependence, older age, and greater comorbidity burden increased mortality risk. Black race, female sex, obesity/overweight, and hematopoietic cell transplantation for patients with MM were protective factors. AO exposure was associated with decreased mortality for both MM/MGUS groups. Transformation increased mortality risk for patients with MGUS and decreased mortality risk for patients with MM. Conclusions: Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and drug use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies should examine the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to best identify their disease course and optimize their care in the latter part of their life.
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Whole-genome sequencing (WGS) of circulating tumour DNA (ctDNA) is now a clinically important biomarker for predicting therapy response, disease burden and disease progression. However, the translation of ctDNA monitoring into vital preclinical PDX models has not been possible owing to low circulating blood volumes in small rodents. Here, we describe the longitudinal detection and monitoring of ctDNA from minute volumes of blood in PDX mice. We developed a xenograft Tumour Fraction (xTF) metric using shallow WGS of dried blood spots (DBS), and demonstrate its application to quantify disease burden, monitor treatment response and predict disease outcome in a preclinical study of PDX mice. Further, we show how our DBS-based ctDNA assay can be used to detect gene-specific copy number changes and examine the copy number landscape over time. Use of sequential DBS ctDNA assays could transform future trial designs in both mice and patients by enabling increased sampling and molecular monitoring.
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DNA Tumoral Circulante , Neoplasias , Animais , Biomarcadores Tumorais , DNA Tumoral Circulante/genética , Efeitos Psicossociais da Doença , Xenoenxertos , Camundongos , Neoplasias/genética , Neoplasias/terapiaRESUMO
Pembrolizumab (Keytruda), an anti-PD-1 antibody used in the treatment of several different malignancies has been identified to cause adverse effects pertaining to multiple body systems which include respiratory, gastrointestinal, dermatologic, and endocrine manifestations known as immune-related adverse events (IRAEs). Skin manifestations have been most described in current literature highlighting the most common adverse effects of this agent. However, adverse outcomes involving the oral mucosa have been rarely identified in the PD-1 and PD-L1 inhibitor classes of immunotherapeutic agents. We present a case of a 71-year-old male who was treated with a chemotherapeutic regimen including pembrolizumab for newly diagnosed squamous cell carcinoma of the lung, who later developed ulcerations on his tongue that were consistent with glossitis. Upon determining that this adverse effect may be immune-related, the patient was treated with oral prednisone 40 mg with a 10 mg taper each subsequent week, which resulted in significant improvement in the patient's symptoms following one month of treatment.
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Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of dysregulated inflammation. It is most commonly seen in children who have a predisposing genetic mutation. However, adults can contract an acquired version of the disorder secondary to an infectious, neoplastic, or other inflammatory insult. There have been several documented cases of HLH being induced by treatment with immunotherapy. Here, we present the case of a 71-year-old man who was receiving pembrolizumab for lung adenocarcinoma when he developed HLH following his 14th cycle of therapy. Although bone marrow biopsy was negative, he nevertheless fulfilled the diagnostic criteria of the HLH 2004 report and was treated with high-dose steroids followed by a prolonged taper, with resolution of his symptoms and normalization of his blood counts.
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OBJECTIVES: The incidence of pancreatic cancer is age dependent. Ninety percent of new diagnoses occur in patients older than 55 years. Despite the association with age and cancer, elderly patients are historically underrepresented in clinical trials. Thus, optimal management of elderly patients has a lack of data. The purpose of this retrospective study was to investigate the outcomes of palliative chemotherapy in elderly patients with pancreatic cancer compared with supportive care alone. METHODS: Unicentric data were reviewed on all elderly patients (defined as age >65 years) with a diagnosis of pancreatic cancer from 2008 through 2019 to compare outcomes in those who received chemotherapy versus supportive care alone. RESULTS: The study reviewed 665 patients with a median age of 75 years (mean, 75.7 years) and average Charlson Comorbidity Score of 5.74. Of them, 291 received chemotherapy and 363 received supportive care only. Chemotherapy was associated with a median overall survival of 250 versus 93 days with supportive care (P < 0.0001). Analysis showed improved survival for all age ranges, cancer stages, and Charlson Comorbidity Scores. CONCLUSIONS: Elderly pancreatic cancer patients can benefit from palliative chemotherapy, and it should be considered, especially in patients with fewer medical comorbidities and better functional status.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde/métodos , Cuidados Paliativos/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Análise de Sobrevida , GencitabinaRESUMO
ABSTRACT: The STarT Back approach comprises subgrouping patients with low back pain (LBP) according to the risk of persistent LBP-related disability, with appropriate matched treatments. In a 12-month clinical trial and implementation study, this stratified care approach was clinically and cost-effective compared with usual, nonstratified care. Despite the chronic nature of LBP and associated economic burden, model-based economic evaluations in LBP are rare and have shortcomings. This study therefore produces a de novo decision model of this stratified care approach for LBP management to estimate the long-term cost-effectiveness and address methodological concerns in LBP modelling. A cost-utility analysis from the National Health Service perspective compared stratified care with usual care in patients consulting in primary care with nonspecific LBP. A Markov state-transition model was constructed where patient prognosis over 10 years was dependent on physical function achieved at 12 months. Data from the clinical trial and implementation study provided short-term model parameters, with extrapolation using 2 cohort studies of usual care in LBP. Base-case results indicate this model of stratified care is cost-effective, delivering 0.14 additional quality-adjusted life years at a cost saving of £135.19 per patient over a time horizon of 10 years. Sensitivity analyses indicate the approach is likely to be cost-effective in all scenarios and cost saving in most. It is likely this stratified care model will help reduce unnecessary healthcare usage while improving the patient's quality of life. Although decision-analytic modelling is used in many conditions, its use has been underexplored in LBP, and this study also addresses associated methodological challenges.
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Dor Lombar , Análise Custo-Benefício , Humanos , Dor Lombar/terapia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Medicina EstatalRESUMO
INTRODUCTION: Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia. CASE REPORT: A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia.Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk. DISCUSSION: Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors' knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.
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Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Hipocalcemia/induzido quimicamente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Cálcio/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/uso terapêuticoRESUMO
Within the Central Texas Veterans Health Care System, the alcohol-related disorder readmission rate has been recognized as an area that needs improvement. The aim of this quality improvement initiative was to develop an alcohol detoxification protocol. This protocol assesses the need for inpatient vs outpatient management of alcohol withdrawal and provides guidance pertaining to medication options, with emphasis on prescribing gabapentin for treatment of alcohol withdrawal. The protocol also contains the alcohol detox e-consult, which prompts a physician to call the patient daily to assess alcohol withdrawal, ability to abstain from alcohol, medication compliance, interest in substance abuse treatment programs, and appropriate follow-up. After implementing the protocol and e-consult, we saw a reduction in the admission rate of alcohol-related disorders and patients found the consult helpful.
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Patients with cirrhosis and splenomegaly commonly develop cytopenias and require the transfusion of blood products. In this study, we evaluated spleen size as a clinical indicator for red blood cell transfusion effectiveness and hypothesized that transfusion would be less effective in patients with splenomegaly. Our retrospective cohort study compared 215 cirrhotic patients with splenomegaly and 114 cirrhotic patients without splenomegaly and measured their respective change in hemoglobin concentration after a unit of transfused red blood cells. The primary endpoint was the percent difference between the measured rise in hemoglobin after transfusion in these cohorts. Patient sex (P < 0.0035), body mass index (P < 0.0001), and the change in hemoglobin concentration after a leukocyte-reduced red blood transfusion (P < 0.0001) were found to be significantly related to spleen size. When compared to the nonsplenomegaly cohort, it was found that the splenomegaly cohort experienced 79.70% (95% CI 71.26%-89.14%) of the change in hemoglobin concentration after red blood cell transfusion when adjusted for patient sex and body mass index. In conclusion, in patients with cirrhosis, increased spleen size was correlated with a decreased responsiveness to red blood cell transfusion when adjusted for patient sex and body mass index.
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Interhospital transfers are independently associated with inpatient mortality, and transferred patients have worse outcomes. The aim of this study was to retrospectively assess the 48-hour mortality rate in interhospital transfer cohorts of all transfers to a Central Texas teaching hospital and to identify a primary admitting diagnosis for potential intervention. A total of 15,435 patients with 19,161 transfers over the course of the study were retrospectively reviewed and placed in 18 different categories based upon the primary admitting diagnosis. There were about 5000 transfer patients yearly with â¼1.4% deaths within 48 hours of arrival. The three leading categories for transferred patients were cardiovascular, neurologic, and psychiatric. In this group, 268 of 19,161 transfers died within 48 hours of arrival. Despite being the 10th leading category for transfer, sepsis was the leading primary admitting diagnosis of patients who died within 48 hours of arrival, accounting for nearly 22% of those patients. Given the significant association found between sepsis and 48-hour mortality after transfer, we devised a novel interhospital transfer checklist based upon the Surviving Sepsis guidelines in an attempt to decrease mortality associated with these transfers.
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The aim of this study was to promote nursing and practitioner satisfaction by improving communication and reducing rapid response team (RRT) activations and code blues hospitalwide by implementing the nursing cheat sheet, a list of key steps to be done before calling the primary provider. This prospective observational study took place over a year at a 636-bed teaching hospital in Central Texas. Education regarding the nursing cheat sheet was provided to nurses at monthly meetings, unit huddles, and interdisciplinary rounds. Units received monthly follow-up education and reminders, and the nursing cheat sheet was posted at nursing work areas. RRT activations and code blues were counted daily. After implementing the nursing cheat sheet, RRT activations were lower than the pre-intervention average and were outside the control band for July, August, and November. The number of code blues did not deviate from the control bands. The authors did not see a reduction in code blues after implementation of the nursing cheat sheet, but the average number of RRT activations decreased, indicating a significant difference in the number of RRT activations. It is not clear that this decrease was due to the intervention.
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BACKGROUND: Low back pain (LBP) and sciatica place significant burden on individuals and healthcare systems, with societal costs alone likely to be in excess of £15 billion. Two recent systematic reviews for LBP and sciatica identified a shortage of modelling studies in both conditions. OBJECTIVES: The aim of this systematic review was to document existing model-based economic evaluations for the treatment and management of both conditions; critically appraise current modelling techniques, analytical methods, data inputs, and structure, using narrative synthesis; and identify unresolved methodological problems and gaps in the literature. METHODS: A systematic literature review was conducted whereby 6512 records were extracted from 11 databases, with no date limits imposed. Studies were abstracted according to a predesigned protocol, whereby they must be economic evaluations that employed an economic decision model and considered any management approach for LBP and sciatica. Study abstraction was initially performed by one reviewer who removed duplicates and screened titles to remove irrelevant studies. Overall, 133 potential studies for inclusion were then screened independently by other reviewers. Consensus was reached between reviewers regarding final inclusion. RESULTS: Twenty-one publications of 20 unique models were included in the review, five of which were modelling studies in LBP and 16 in sciatica. Results revealed a poor standard of modelling in both conditions, particularly regarding modelling techniques, analytical methods, and data quality. Specific issues relate to inappropriate representation of both conditions in terms of health states, insufficient time horizons, and use of inappropriate utility values. CONCLUSION: High-quality modelling studies, which reflect modelling best practice, as well as contemporary clinical understandings of both conditions, are required to enhance the economic evidence for treatments for both conditions.
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Técnicas de Apoio para a Decisão , Dor Lombar/economia , Ciática/economia , Análise Custo-Benefício , Humanos , Dor Lombar/terapiaRESUMO
OBJECTIVE: To examine how provider report of confidential consultation in the electronic health record is associated with adolescent characteristics, health risk factors, and provider training. STUDY DESIGN: This prospective cohort study was conducted as part of a larger study implementing computerized clinical decision support in 2 urban primary care clinics. Adolescents used tablets to complete screening questions for specified risk factors in the waiting room. Adolescent-reported risk factors included sexual activity, substance use, and depressive symptoms. Providers were prompted on encounter forms to address identified risk factors and indicate whether confidential consultation was provided. Provider types included adolescent medicine board certified pediatrics and general pediatrics. Differences in proportions of adolescents reporting risk factors by provider type were assessed using χ2 tests. Associations between adolescent characteristics, risk factors, and provider-reported confidential consultation were examined using logistic regression analyses. RESULTS: The sample included 1233 English and Spanish-speaking adolescents 12-20 years of age (52% female; 60% black; 50% early adolescent). Patients seen by adolescent medicine board certified providers reported sexual activity, depressive symptoms, and substance use significantly more often than those seen by general pediatric providers. Among patients seen by board certified adolescent medicine providers, confidential consultation was provided to 90%. For those seen by general pediatric providers, confidential consultation was provided to 53%. Results of multiple logistic regression demonstrated that female sex, later adolescence, and clinic location were significantly associated with confidential consultation. CONCLUSIONS: Provider training is needed to reinforce the importance of confidential consultation for all adolescents.
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Serviços de Saúde do Adolescente/organização & administração , Medicina do Adolescente/métodos , Confidencialidade , Relações Médico-Paciente/ética , Atenção Primária à Saúde/ética , Encaminhamento e Consulta/ética , Inquéritos e Questionários , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKß contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here, we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphologic changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent antiproliferative effects with greatest activity in hematologic cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy.Significance: The development of selective small-molecule inhibitors of the Cdc42-binding MRCK kinases reveals their essential roles in cancer cell viability, migration, and invasive character. Cancer Res; 78(8); 2096-114. ©2018 AACR.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Descoberta de Drogas , Miotonina Proteína Quinase/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/enzimologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Células HEK293 , Humanos , Camundongos , Camundongos Nus , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Neoplasias Cutâneas/enzimologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: The purpose of this study was to assess the feasibility of using an existing computer decision support system to screen adolescent patients for suicidality and provide follow-up guidance to clinicians in a primary care setting. Predictors of patient endorsement of suicidality and provider documentation of follow-up were examined. METHODS: A prospective cohort study was conducted to examine the implementation of a CDSS that screened adolescent patients for suicidality and provided follow-up recommendations to providers. The intervention was implemented for patients aged 12-20 years in two primary care clinics in Indianapolis, Indiana. RESULTS: The sample included 2,134 adolescent patients (51% female; 60% black; mean age = 14.6 years [standard deviation = 2.1]). Just over 6% of patients screened positive for suicidality. A positive endorsement of suicidality was more common among patients who were female, depressed, and seen by an adolescent-medicine board-certified provider as opposed to general pediatric provider. Providers documented follow-up action for 83% of patients who screened positive for suicidality. Documentation of follow-up action was correlated with clinic site and Hispanic race. The majority of patients who endorsed suicidality (71%) were deemed not actively suicidal after assessment by their provider. CONCLUSIONS: Incorporating adolescent suicide screening and provider follow-up guidance into an existing computer decision support system in primary care is feasible and well utilized by providers. Female gender and depressive symptoms are consistently associated with suicidality among adolescents, although not all suicidal adolescents are depressed. Universal use of a multi-item suicide screener that assesses recency might more effectively identify suicidal adolescents.
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Sistemas de Apoio a Decisões Clínicas , Programas de Rastreamento/métodos , Atenção Primária à Saúde , Encaminhamento e Consulta , Suicídio/estatística & dados numéricos , Adolescente , Depressão , Feminino , Humanos , Indiana , Masculino , Estudos Prospectivos , Fatores Sexuais , Ideação Suicida , Tentativa de Suicídio/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: When clinicians think about Staphylococcus aureus bacteria, what comes to the mind of most is the dreaded methicillin-resistant form. However, clinicians should not forget the methicillin-susceptible type, which is just as virulent. CASE PRESENTATION: The authors present the case of a 20-year-old woman who was admitted with septic shock and multi-organ failure and was found to have disseminated methicillin-susceptible Staphylococcus aureus (MSSA) infection. The patient had persistent blood cultures positive for MSSA. A transesophageal echocardiogram showed a 1.1 cm vegetation in the mitral valve, and the patient had bilateral pleural effusions that grew MSSA. An MRI of the brain showed multiple areas consistent with infarctions thought to be secondary to septic emboli. The patient underwent a mitral valve replacement and was treated with a prolonged course of parenteral nafcillin. DISCUSSION: This case illustrates a severe clinical presentation and management of MSSA infections.
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Meticilina/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Feminino , Humanos , Nafcilina/uso terapêutico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/efeitos dos fármacos , Adulto JovemRESUMO
PURPOSE: The objective of this study was to determine the effectiveness of computer-based screening and physician feedback to guide adolescent depression management within primary care. METHODS: We conducted a prospective cohort study within two clinics of the computer-based depression screening and physician feedback algorithm among youth aged 12-20 years between October 2014 and October 2015 in Marion County (Indianapolis), Indiana. RESULTS: Our sample included 2,038 youth (51% female; 60% black; mean age = 14.6 years [standard deviation = 2.1]). Over 20% of youth screened positive for depression on the Patient Health Questionnaire-2 and 303 youth (14.8%) screened positive on the Patient Health Questionnaire-9 (PHQ-9). The most common follow-up action by physicians was a referral to mental health services (34.2% mild, 46.8% moderate, and 72.2% severe range). Almost 11% of youth in the moderate range and 22.7% of youth in the severe range were already prescribed a selective serotonin reuptake inhibitor. When predicting mental health service referral, significant predictors in the multivariate analysis included clinic site (40.2% vs. 73.9%; p < .0001) and PHQ-9 score (severe range 77.8% vs. mild range 47.5%; p < .01). Similarly, when predicting initiation of selective serotonin reuptake inhibitors, only clinic site (28.6% vs. 6.9%; p < .01) and PHQ-9 score (severe range 46.7% vs. moderate range 10.6%; p < .001) were significant. CONCLUSIONS: When a computer-based decision support system algorithm focused on adolescent depression was implemented in two primary care clinics, a majority of physicians utilized screening results to guide clinical care.
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Depressão/epidemiologia , Programas de Rastreamento/métodos , Médicos/estatística & dados numéricos , Atenção Primária à Saúde/métodos , Encaminhamento e Consulta , Adolescente , Depressão/etnologia , Feminino , Humanos , Indiana/epidemiologia , Masculino , Prevalência , Fatores de Risco , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inquéritos e Questionários/estatística & dados numéricosRESUMO
Severe vitamin B12 deficiency is caused most commonly by autoimmune atrophic gastritis leading to loss of intrinsic factor. Vitamin B12 deficiency leading to megaloblastic anemia and demyelinating central nervous system disease is well known; however, a rare presentation of B12 deficiency described as pseudothrombotic microangiopathy is not well known. This complication presents with signs of mechanical hemolysis, elevated lactate dehydrogenase (LDH), thrombocytopenia, and a low reticulocyte count, which can be incorrectly diagnosed as thrombotic thrombocytopenic purpura and managed incorrectly. Decreased reticulocyte count and an LDH >2500IU/L is more commonly seen in B12 deficiency. However, recognizing the differences in marked poikilocytosis can be challenging, as seen with megaloblastic changes and true schistocytosis. To illustrate the challenge in differentiating between megaloblastic changes and true schistocytosis, we present the case of a 27-year-old woman who presented to her physician for symptomatic anemia and complaints of nausea, vomiting, and loose stool. She had a hemoglobin of 5.1g/dL, platelet count of 39×109/L, LDH of 9915IU/L, haptoglobin below assay limit, and a reticulocyte count of 2.5%. Peripheral smear showed macrocytic anemia, rare hypersegmented neutrophils, and schistocytes. Vitamin B12 level was less than 50pg/mL, methylmalonic acid was 0.33µmol/L, anti-parietal cell antibody was >1:640, and intrinsic factor blocking antibody was positive-confirming the diagnosis of pernicious anemia. While hospitalized, she was treated with vitamin B12 1000µg intramuscular injections daily and thereafter continued with monthly injections, which ultimately resolved her severe macrocytic anemia.
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Anemia Perniciosa , Deficiência de Vitamina B 12 , Vitamina B 12/administração & dosagem , Adulto , Anemia Perniciosa/sangue , Anemia Perniciosa/diagnóstico , Anemia Perniciosa/tratamento farmacológico , Anemia Perniciosa/etiologia , Feminino , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Contagem de Plaquetas , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológicoRESUMO
The purpose of this study was to evaluate alcohol-based dispensers as potential fomites for Clostridium difficile. A convenience sample of 120 alcohol-based dispensers was evaluated for the presence of C difficile either by culture or polymerase chain reaction for C difficile toxin. The results demonstrated that C difficile was not cultured, and C difficile toxin was not detected using polymerase chain reaction; however, gram-positive rods, Clostridium perfringens, Pantoea agglomerans, coagulase-negative Staphylococcus, Peptostreptococcus, Bacillus spp, and microaerophilic Streptococcus were present within the overflow basins of the alcohol-based dispensers.