Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality.
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ABSTRACT:
SUBMITTER: Akhgari M
PROVIDER: S-EPMC5488824 | biostudies-other | 2017 May
REPOSITORIES: biostudies-other
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Project description:Thymomas consist of neoplastic thymic cells intermixed with variable numbers of non-neoplastic lymphocytes. Metastatic thymomas are typically managed with non-curative chemotherapy to control tumor-related symptoms; no prolonged survival is expected. Metabolic-based approaches, such as fasting and ketogenic diets, target cancer cell metabolism by creating an increased reliance on ketones while decreasing glucose, glutamine, and growth factor availability, theoretically depriving cancer cells of their metabolic fuels while creating an unfavorable environment for cancer growth, which may be beneficial in metastatic thymoma. We report the case of a 37-year-old woman with myasthenia gravis, diagnosed with an inoperable type AB, stage IVA thymoma, who pursued a metabolic intervention consisting of periodic fasting (7-day, fluid-only fasts every 1-2 months), combined with a modified ketogenic diet on feeding days, for 2 years. Fasting-related adverse effects included cold intolerance, fatigue, and generalized muscle aches, all of which resolved during the second year. She experienced two myasthenia relapses, each associated with profoundly reduced oral intake, marked weight loss, and tumor regression-the first relapse was followed by a 32% decrease in tumor volume over 4 months, the second relapse by a dramatic 96% decrease in tumor volume over 4 months. The second relapse also required prednisone to control the myasthenia symptoms. We hypothesize that 2 years of fasting and ketogenic diet therapy metabolically weakened the neoplastic thymic cell component of the thymoma, "setting the stage" for immune activation and extreme energy restriction to destroy the majority of cancer cells during both relapses, while prednisone-induced apoptosis eradicated the remaining lymphocytic component of the thymoma during the second relapse. This case is unique in that a metabolic-based fasting and ketogenic diet intervention was used as the primary management strategy for a metastatic cancer in the absence of surgery, chemotherapy, or radiotherapy, culminating in a near-complete regression. Nearly 3 years after being diagnosed with inoperable metastatic cancer, our patient shows no signs of disease and leads a full and active life.
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Project description:BackgroundEffective responses to the worsening drug overdose epidemic require accurate and timely drug overdose surveillance data. The objectives of this paper are to describe the development, functionality, and accuracy of the Suspected Potential Overdose Tracker (SPOT) for predicting accidental drug overdose as the cause and manner of death in near real-time, and public health implications of adopting the tool.MethodsSPOT was developed to rapidly identify overdose deaths through a simple and duplicable process using data collected by death investigators. The tool assigns each death a ranking of 1 through 3 based on the likelihood of it being an unintentional drug overdose, with 1 representing the highest likelihood that the death will be confirmed as an unintentional drug overdose and 3 representing the lowest. We measured the accuracy of the tool for predicting overdose deaths by comparing potential overdose deaths in New York City from 2018-2020 that were identified using SPOT to finalized death certificates. We also calculated the proportion of death certificate-confirmed overdoses that were missed by the SPOT tool and the proportion of type 1 errors.ResultsSPOT captured up to 77% of unintentional drug overdose deaths using data collected within 72 h of fatality. The tool predicted unintentional drug overdose from 2018 to 2020 with 93-97% accuracy for cases assigned a ranking of 1, 87-91% accuracy for cases assigned a ranking of 2, and 62-73% accuracy for cases assigned a ranking of 3. Among all unintentional overdose deaths in 2018, 2019, and 2020, 21%, 28%, and 33% were missed by the SPOT tool, respectively. During this timeframe, the proportion of type 1 errors ranged from 15%-23%.ConclusionsSPOT may be used by health departments, epidemiologists, public health programs, and others to monitor overdose fatalities before death certificate data becomes available. Improved monitoring of overdose fatalities allows for rapid data-driven decision making, identification of gaps in public health and public safety overdose response, and evaluation and response to overdose prevention interventions, programs, and policies.
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Project description:BackgroundIsolated pulmonary valve endocarditis is a very rare form of right-sided infective endocarditis. Due to the anatomy, in most cases, just the tricuspid valve is involved. Diagnosis can be challenging because of non-specific symptoms (fever, dyspnoea, haemoptysis, and pleuritic chest pain) and difficulty of detection by echocardiography. Risk factors include intravenous drug abuse, congenital heart disorders, alcohol abuse, male sex and central venous catheters, or pacemaker leads.Case summaryA 39-year-old homeless male patient, who was a current intravenous drug user, presented with fever, dyspnoea, and haemoptysis. The chest X-ray showed bilateral infiltrates. Empiric antibiotic treatment was initiated. Blood cultures showed the presence of Streptococcus dysgalactiae. Atypical causes of pneumonia were excluded. Systemic embolism was suspected, and a computed tomography scan of brain, thorax, and abdomen was performed. Multiple septic embolic lesions were detected in both lungs. Echocardiography revealed an isolated pulmonary valve endocarditis. Penicillin G and gentamycin were administered intravenously for a duration of 6 and 2 weeks, respectively. The patient was discharged in stable condition but did not return for outpatient clinical appointments.DiscussionTo detect rare causes of right-sided infective endocarditis, repeated echocardiograms with special focus on the pulmonary valve may be required. Usually, antibiotic treatment alone leads to recovery. In special situations (heart failure, septic shock, or large vegetation size) surgery is required. Due to the high risk of postoperative complications, surgery in intravenous drug users should be avoided if possible.
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| PRJNA498747 | ENA
Project description:BackgroundOverdose deaths have increased dramatically in the United States and are often attributed to prescription opioids. This study presents a framework for “overdose typologies”, including non-medical prescription drug use, to more accurately describe drug use patterns.MethodsThis study examined linked prescription drug monitoring program (PDMP) and toxicology data (2016–2018) from accidental overdose deaths from a large metropolitan coroner’s office in the Midwest (Indianapolis, Indiana).ResultsIn total, 1,112 accidental overdose deaths occurred and over two-thirds (68.0%; n = 756) were coded as an illicit drug user with no prescription opioid present in the toxicology. The most infrequent categories were prescription opioid users 5.5% (n = 61).ConclusionLinked PDMP and toxicology reports are useful in identifying drug use patterns that contribute to mortality.
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Project description:BackgroundCocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine.Case presentationA 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly.ConclusionThe exact incidence of cocaine related cardiomyopathy is unknown and likely underreported. The clinical course is abrupt and comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however β-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response.
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Project description:IntroductionLevothyroxine (T4) overdose is not frequently encountered and for the clinical signs to materialize, the ingested dose, the rate of conversion of T4 to T3 and chronicity of overdose can be held accountable.Case reportA 29-year-old female, a known case of hypothyroidism and adjustment disorder, under levothyroxine, propranolol and sertraline, intentionally ingested 2.5 mg of levothyroxine but remained asymptomatic with sudden surge in T4 in initial hours of ingestion which gradually started declining along with reciprocal change in TSH. However, the change in T3 was almost negligible.DiscussionT3, the active thyroid hormone, when in excess accounts for toxic effects. The duration during physiological process of deiodination and half life of hormone correlates with onset and duration of symptoms. Propranolol which blocks peripheral conversion of T4 to T3 and sertraline which is also reported to reduce the efficacy of levothyroxine, which is evident from low T3 in thyroid profile, must have led to patient being asymptomatic despite lack of early gastric decontamination.ConclusionLevothyroxine overdose up to 4mg/day may be asymptomatic but in patients with concomitant neurotic or psychiatric illness, who intentionally take it, are also put on drugs like sertraline and propranolol, the effects of which on thyroid hormones must be contemplated for possible explanation of being asymptomatic.
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Project description:Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression. Background: Despite of extensive research the genetic component of extremely low birth weight in newborns has remained obscure. Results: The aim of the case study was to identify candidate gene(s) causing extremely low birth weight (ELBW) in newborns and hypotrophy in infants. A four-member family was studied: mother, father and two ELBW-phenotype children. The studies were carried out due to the medical conditions of the second child at birth and post-partum: peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy, and suspicion of metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 differentially expressed, with the level of the transcript significantly lower in blood samples of children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion: We showed the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 (chromosome 14 open reading frame 132) gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the developmental delay through the altered gene expression.
2016-08-01 | GSE85013 | GEO