Auto-Brewery Syndrome After COVID-19 Infection.

Auto-brewery syndrome (ABS) is a rare medical condition, wherein gut microbiota ferment carbohydrates to alcohol. Risk factors for ABS include diets high in carbohydrates and sugars, diabetes mellitus, prior gastrointestinal surgery, nonalcoholic fatty liver disease, and certain genetic mutations, among others. We provide a case of ABS that developed after known COVID-19 infection, which may be one of the contributing factors to its development.

Optimised conformal total body irradiation: a heterogeneous practice, so where next?

The use of volumetric arc therapy and inverse planning has been in routine use in radiotherapy for two decades. However, use in total body irradiation (TBI) has been more recent and few guidelines exist as to how to plan or verify. This has led to heterogeneous approaches. The goal of this review is to provide an overview of current advanced planning and dosimetry verification protocols used in optimised conformal TBI as a basis for investigating the need for greater standardisation in TBI.

Application of failure mode and effects analysis to validate a novel hybrid Linac QC program that integrates automated and conventional QC testing.

A hybrid quality control (QC) program was developed that integrates automated and conventional Linac QC, realizing the benefits of both automated and conventional QC, increasing efficiency and maintaining independent measurement methods. Failure mode and effects analysis (FMEA) was then applied in order to validate the program prior to clinical implementation. The hybrid QC program consists of automated QC with machine performance check and DailyQA3 array on the TrueBeam Linac, and Delta4 volumetric modulated arc therapy (VMAT) standard plan measurements, alongside conventional monthly QC at a reduced frequency. The FMEA followed the method outlined in TG-100. Process maps were created for each treatment type at our center: VMAT, stereotactic body radiotherapy (SBRT), conformal, and palliative. Possible failure modes were established by evaluating each stage in the process map. The FMEA followed semiquantitative methods, using data from our QC records from eight Linacs over 3 years for the occurrence estimates, and simulation of failure modes in the treatment planning system, with scoring surveys for severity and detectability. The risk priority number (RPN) was calculated from the product of the occurrence, severity, and detectability scores and then normalized to the maximum and ranked to determine the most critical failure modes. The highest normalized RPN values (100, 90) were found to be for MLC position dynamic for both VMAT and SBRT treatments. The next highest score was 35 for beam position for SBRT, and the majority of scores were less than 20. Overall, these RPN scores for the hybrid Linac QC program indicated that it would be acceptable, but the high RPN score associated with the dynamic MLC failure mode indicates that it would be valuable to perform more rigorous testing of the MLC. The FMEA proved to be a useful tool in validating hybrid QC.

Evaluation of Urinary Biomarkers of Proximal Tubular Injury, Inflammation, and Fibrosis in Patients With Albuminuric and Nonalbuminuric Diabetic Kidney Disease.

INTRODUCTION: Albuminuric and nonalbuminuric pathways contribute to diabetic kidney disease. Proximal tubule and inflammation play important roles in these processes. Urinary biomarker(s) to detect early kidney damage and predict progression are needed. METHODS: Nine urinary biomarkers were measured at baseline in 400 patients with diabetes. Correlation and multivariate logistic and linear regression analyses were performed to assess the association of biomarkers with chronic kidney disease and progression. RESULTS: In the albumin/creatinine ratio (ACR) <3 cohort, the only biomarker significantly associated with estimated glomerular filtration rate < 60 ml/min was N-acetyl-ß-d-glucosaminidase. A combination of ACR and monocyte chemoattractant protein 1 (MCP1) were significantly associated with stage 2 chronic kidney disease in this cohort. Logistic models showed that in patients with all levels of albuminuria, ACR, retinol binding protein (RBP), and MCP1 were associated with progression. A model including MCP1, interleukin 6, and neutrophil gelatinase-associated lipocalin showed significant association with progression to chronic kidney disease 3/4 in the ACR <3 cohort. Linear mixed-model regression analyses demonstrated MCP1, RBP, and ACR as significant proteins associated with progression to stage 3 or worse, whereas MCP1 was the only significant biomarker in the ACR <3 cohort. Time-to-event and Cox proportional hazard models confirmed significant hazard ratios for progression for ACR, RBP, and MCP1, with significant differences noted between quantiles of biomarkers for ACR, RBP, and MCP1. CONCLUSION: In this study of diabetic patients with single baseline measurements of urinary biomarkers, albumin, RBP, and MCP1 were significantly associated with chronic kidney disease progression at all levels of albuminuria. Inflammatory cytokines, neutrophil gelatinase-associated lipocalin, and MCP1 were associated with progression in patients without albuminuria. N-acetyl-ß-d-glucosaminidase demonstrated a significant association with an estimated glomerular filtration rate < 60 ml/min in the ACR <3 cohort.

Alcohol and cocaine use prior to suspected suicide: Insights from toxicology.

INTRODUCTION: This study investigates whether there is a relationship between alcohol and cocaine use in deaths where suicide by self-injury is the suspected cause of death. METHODS: Adults referred by coroners to the Imperial College London Toxicology Unit for toxicological analysis between 2012 and 2016 were reviewed for inclusion criteria. Those who died by self-injury reasoned to be deliberate were included in the analysis. Femoral blood alcohol concentration (BAC) and presence of cocaine or benzoylecognine (a metabolite of cocaine) in blood and/or urine were tabulated and odds ratios calculated. RESULTS: A total of 1722 decedents met inclusion criteria. BAC was ≥50 mg/dL in 29% of decedents. Cocaine was detected in 8.4% of cases. The likelihood of testing positive for cocaine increased with BAC and was most frequent between 100 and 199 mg/dL, consistent with moderate to severe intoxication (odds ratio 5.88, 95% confidence interval 3.80, 9.09; P ≤ 0.001) compared to those with BAC <10 mg/dL. DISCUSSION AND CONCLUSIONS: This study demonstrates a correlation between increasing BAC and likelihood of cocaine use prior to suspected suicide, up to a level consistent with severe intoxication. Cocaine use was found in a high proportion of cases relative to the general population reporting regular use. This pattern of drug and alcohol use has previously been given little attention in suicide prevention strategies and clinical prioritisation.

Scorpion Stings and Antivenom Use in Arizona.

BACKGROUND: Arizona's rugged desert landscape harbors many venomous animals, including a small nocturnal scorpion, Centruroides sculpturatus, whose venom can cause severe neuromotor disturbance. An effective antivenom is available at selected health care facilities in the state. METHODS: We analyzed 4398 calls of scorpion stings to the Arizona Poison and Drug Information Center (APDIC) in Tucson over a period of 3 years, from January 2017 to December 2019. RESULTS: We followed 1952 (44.4%) of the victims to resolution. We excluded 2253 callers with minimal effects of the sting and 193 victims with possible toxic effects who were lost to follow-up. The most common complaints among callers were pain at the sting site in 88.9% and local numbness in 62.2%. Detailed clinical information was obtained from 593 calls from a health care facility. Neuromotor signs consistent with C. sculpuratus envenomation included nystagmus in 163 (27.5%), hypersalivation in 91 (15.3%), and fasciculations in 88 (14.8%). Antivenom (Anascorp; Rare Disease Therapeutics, Inc., Franklin, Tenn) was administered to 145 patients. Most were children <5 years old (n = 76, or 54.4%); 27 (18.6%) were 5-9 years old and 42 (30.0%) were ≥10 years of age. About half, 79 of 145 (54.5%) victims who received antivenom, met the APDIC recommended use criteria. CONCLUSIONS: Patients treated with antivenom exhibited a rapid resolution of symptoms without immediate or delayed hypersensitivity reactions. We recommend broadened availability of antivenom at sites where it is most needed.

Total skin electron beam therapy rationalization and utility of in vivo dosimetry in a high-volume centre.

OBJECTIVE: This paper reports on the rationalization of a substantial pool of in vivo dosimetry (IVD) data from patients treated with total skin electron beam therapy (TSEBT) and the application of this to verify the accurate delivery of TSEBT when changing linac manufacturer. METHODS: Thermoluminescent dosimeter IVD data from 149 patients were analyzed comparing the population mean and standard deviation for each site. The number of sites required to confirm the prescribed dose were reviewed considering both dosimetric and clinical relevance. The reduced sites were then used to assess the continued dosimetric accuracy on new equipment and the results were compared statistically using the Mann-Witney test. RESULTS: The trunk dose measurement points were reduced from nine to six and five extra trunk sites were identified and reviewed clinically prior to removal.Following change in manufacturer the trunk dose points showed no statistically significant change and confirmed that patients had received within 1.3% of the intended mean trunk dose using both delivery methods.A statistically significant change in 4 out of the 13 extra trunk sites was seen following the move to the new centre. However, all but one site showed a change of less than 1 standard deviation. CONCLUSION: The total number of measurement points per patient were reduced from 27 to 19 which constituted a 25% saving in preparation and read out.Accurate delivery of prescribed dose was confirmed following measurement point reduction for treatments delivered on linacs from two different manufacturers. ADVANCES IN KNOWLEDGE: Proven methodology for rationalization of IVD measurements for TSEBT.

Violence among persons diagnosed with schizophrenia: how pharmacists can help.

Violence among those diagnosed with schizophrenia has been reported but is not a diagnostic component of the disorder. The position of the courts regarding fulfillment of the requisite intent to commit violent acts has not been extensively reported. This article discusses the impact of a diagnosis of schizophrenia in an individual and how the pharmacist can help integrate information into the health care system. The recent Supreme Court case of Clark versus Arizona and the older case of Patterson versus Cockrell are discussed with respect to the concept of intent (to commit the act) and the implications this has on an individual in the midst of a psychotic episode. Quality of life, the perception of the stigma associated with a diagnosis of schizophrenia, and pharmacotherapy are briefly discussed. The origin of schizophrenia is multifactorial. Persons with schizophrenia are not innately violent, but alteration in perception may precipitate aggressive acts. Given the complex and diverse nature of schizophrenia and the fact that even with successful pharmacological treatment residual symptoms may still be present, there is a need to provide information to health care practitioners and the court.

CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa.

BACKGROUND: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. METHODS AND FINDINGS: Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. CONCLUSIONS: To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.

Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials.

BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.