A Case of Multidrug-Resistant Tuberculosis in an Active Duty Military Health Care Worker.

Cases of active tuberculosis (TB) in the U.S. Military have fallen over the last century in large part due to improved screening and treatment options. The subset of multidrug-resistant TB (MDR-TB) is almost nonexistent within the U.S. Military. We present a case of MDR-TB in an active duty U.S. Military health care worker and discuss several considerations for treatment that may present challenges for U.S. Military medical practitioners. A 30-year-old active duty Soldier was referred to Army public health services after a bronchoscopy sample was positive for Mycobacterium tuberculosis complex. Sputum smears were negative for acid-fast bacilli, suggesting lower risk for community spread. One month after initiation of the standard 4-drug regimen for active TB, genetic susceptibility testing found the patient's M. tuberculosis isolate to be resistant to rifampin, isoniazid, and pyrazinamide. Contact investigation efforts among co-workers and family members fortunately found no new interferon-gamma release assay conversions. Coordination of public health assets to ensure a successful treatment regimen occurred across varied local, state, and federal agencies. Atypical medications required coordination with the FDA for procurement. An extensive surveillance plan for medication adverse effects was required. Finally, questions of public health authority versus patient autonomy arose requiring multidisciplinary input and ethical discussions.

Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users.

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI.

Evaluation of Strontium Interference in Calcium Measurement Procedures and Content in Supplements as Measured by ICP-MS.

BACKGROUND: Bone health supplements containing strontium are available without prescription, however, the effects of strontium interference on clinical laboratory calcium measurement procedures are unknown. METHODS: To evaluate strontium interference on total calcium measurements, plasma pools with exogenously added strontium were measured by 3 total calcium measurement procedures. For ionized calcium measurements, whole blood pools prepared with exogenously added strontium were measured by 2 ionized calcium measurement procedures. An inductively coupled plasma mass spectrometry assay (ICP-MS) was validated for research measurements of strontium content in commercially available supplements. RESULTS: Exogenous strontium addition to plasma caused positive bias for total calcium measurements. Strontium concentrations of 1.0 mg/dL (0.114 mmol/L), 2.5 mg/dL (0.284 mmol/L), and 5.0 mg/Dl (0.568 mmol/L) resulted in mean biases of 1.9% to 3.5%, 4.9% to 9.0%, and 10.8% to 19.2%, respectively, for total calcium measurement procedures. Biases for ionized calcium measurements were less than 4.5% for a strontium concentration of 5.0 mg/dL (0.568 mmol/L). An in-house-developed ICP-MS assay for strontium in commercially available supplements exhibited within-laboratory and within-run coefficients of variation of less than 3%, and a linear response was obtained over the assay analytical measurement range of 10 to 100 000 ng/mL (0.0001 to 1.141 mmol/L). Strontium recovery for the ICP-MS assay was 97.1% to 105.3%. The largest amount of strontium measured in dietary supplements was 395 mg in a 1054 mg tablet. CONCLUSIONS: Some dietary supplements contain larger amounts of strontium than indicated on the product label. High concentrations of strontium may cause significant interference for total calcium measurement procedures, but ionized calcium measurement procedures are not significantly affected.

Forage and You Shall Find: Cardiac Glycoside Poisoning and the Danger of Foraging.

Amateur foraging, which can be described as the gathering of uncultivated plants for sustenance or recreation, supports many benefits for the forager and the environment; however, it can also present the hazard of unintentional poisoning. Asclepias syriaca, or common milkweed, is a potentially edible plant that also contains cardioactive steroids akin to digoxin. A 38-year-old female amateur forager boiled and sautéed 8-10 milkweed pods before ingesting them. She developed vomiting and heart palpitations within 1 hour and presented to an emergency department 3 hours after ingestion. Her exam was within normal limits with exception of heart rate in the 40-50s without hypotension. ECG was notable for sinus bradycardia. Laboratory analysis was notable for a detectable serum digoxin concentration. Life-threatening toxicity did not occur. Recently, some military services have advocated for foraging as a means to sustain far-forward troops. However, misidentification of plants by inexperienced foragers can result in severe toxicity or death. If mass foraging becomes part of expeditionary operations, military clinicians must be trained and prepared for the potentially severe plant-related poisonings.

Descriptive epidemiology of clinically significant occupational poisonings, United States, 2008-2018.

INTRODUCTION: References listing common occupational poisons often include agents that were observed decades prior to the introduction of worker protective laws and regulations. Current causes of work-related acute poisonings have not been characterized. This study's primary objective was to describe the most common poisons and routes of exposure responsible for clinically significant occupational poisonings. A secondary objective was to determine the crude rate of clinically significant occupational poisonings and occupational poisoning-related deaths over the study period. METHODS: This was a retrospective cohort study using electronic data from the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS), and open source data from the United States Bureau of Labor Statistics (BLS). The NPDS was queried for all cases with exposure reason coded as "Unintentional-Occupational" for the period 1 January 2008 to 31 December 2018. A case of clinically significant occupational poisoning (CSOP) was defined as a case with moderate or severe clinical effects reported, to include fatal cases. A descriptive analysis was conducted using unadjusted odds ratios to assess the strength of association between main variables of interest and CSOP. RESULTS: 329,437 exposure cases were available for analysis. Of these, 54,254 were considered CSOP and included 196 deaths. The top five poisons responsible for occupational fatalities were hydrogen sulfide, ammonia, carbon monoxide, simple asphyxiants, and chlorines. Fatalities were 3.7 times (OR: 3.7; 95% CI: 2.2-6.4) more likely to be men and 5.7 times (OR: 5.7; 95% CI: 4.0-8.1) more likely to have had an inhalational exposure, compared to those workers with CSOP without fatality. The crude rate of occupational fatal poisoning reported to US poison centers was 11.3 deaths per 100,000,000 worker-years during the study period. The crude rate of clinically significant occupational poisoning was 3.1 per 100,000 worker-years. These rates remained generally stable over the study period. CONCLUSION: Occupational poisonings continue to be a significant cause of morbidity and mortality in the workplace despite significant improvements in workplace chemical safety over the last four decades. Workplace education and proper preventive measures devoted to inhalational toxicants and respiratory protection are opportunities for improvement.

Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine.

BACKGROUND: Recent recognition of "massive" acetaminophen (APAP) overdoses has led to the question of whether standard dosing of N-acetylcysteine (NAC) is adequate to prevent hepatoxicity in these patients. The primary aim of this study was to evaluate the clinical outcome for patients with massive APAP overdose who received standard intravenous NAC dosing of 300 mg/kg over 21 h. METHODS: This was a single-center retrospective cohort study conducted by chart review of APAP overdoses reported to a regional poison center from 1 January 2010 to 31 December 2019. Massive APAP overdose was defined by single, acute overdose resulting in an APAP concentration exceeding 300 mcg/mL at 4 h post-ingestion. Standard univariate statistical analysis was conducted to describe the cohort, and a multivariate logistic model was utilized to calculate adjusted odds ratios for risk of hepatoxicity. RESULTS: 1425 cases of APAP overdose were reviewed. 104 cases met the inclusion criteria of massive APAP overdose. Overall, 79 cases (76%) had no acute liver injury or hepatotoxicity, and 25 (24%) developed hepatoxicity. Nine percent (n = 4) of cases receiving NAC within 8 h developed hepatotoxicity. Crude odds for hepatoxicity was 5.5-fold higher for cases who received NAC after 8 h. CONCLUSIONS: Standard NAC dosing received within 8 h prevented hepatoxicity in 91% (n = 40) of cases in our series of massive APAP overdoses. Additional data is needed to determine the clinical outcomes of massive APAP overdose using current intravenous NAC dosing.

"Road Rash" and Dizziness: A Case of Hemodynamically Significant Topical Clonidine Toxicity.

Clonidine is a central alpha-2 agonist well known to produce a syndrome of bradycardia and hypotension in overdose. However, few examples of overt clinical clonidine toxicity secondary to cutaneous absorption have been reported. We report a case of unintentional systemic clonidine toxicity in an adult because of a compounded preparation of clonidine applied to a degraded skin barrier. A 35-year-old male suffered a motorcycle accident 48 hours before presentation resulting in an abrasion to his distal left leg. On the day of presentation, he self-treated the wound by repeated application of a family member's pain-relieving cream. Later he was found confused and unable to stand by a family member. The family member recognized the thick visible coat of cream as the likely cause and decontaminated the patient while calling 911. Prehospital vitals were notable for a blood pressure of 80/30 mm Hg and heart rate of 38 beats per minute. In the emergency department, the patient was resuscitated with intravenous fluids with resultant normalization of blood pressure. Upon later review, the cream was determined to have been created by a local compounding pharmacy for the use in neuropathic pain and was labeled to contain clonidine, lidocaine, ketamine, and gabapentin. Cutaneous absorption of the pain cream was greatly increased because of loss of skin integrity. Military physicians and compounding pharmacies should ensure that patients are aware of the proper application of compounded creams and the potential risk for systemic toxicity with overuse or degraded skin.

Atypical systemic and dermatologic loxoscelism in a non-endemic region of the USA.

INTRODUCTION: Loxosceles reclusa (LR), commonly known as the brown recluse spider, is endemic to the south central United States. We present a case of LR envenomation in a healthy adult male outside the usual geographic range, with atypical dermatologic and delayed, prolonged systemic loxoscelism (LX). This case demonstrates the importance of expanding the depth of knowledge of LR envenomations. CASE REPORT: A previously healthy 27 year-old male presented to an emergency department (ED) in central Virginia two hours after a LR envenomation to his left proximal arm. He was treated with diphenhydramine and discharged on oral methylprednisolone for a 5-day taper. On post-bite Days 1 and 2, the patient developed subjective fevers, chills, arthralgias, and myalgias, followed by a blanching, pruritic, morbilliform rash throughout his trunk and lower extremities. Post-bite Day 3, the patient presented to the ED again because of marked erythema of face and the right lateral thigh, and posterior and anterior trunk. Vital signs and laboratory analysis were generally unremarkable. The patient was observed overnight, and discharged with a prescription for prednisone 60 mg per day. On post-bite Day 7, the patient noted a petechial rash on the palms and soles and returned to the ED with a fever of 102.6 °F, a heart rate of 130 beats per minutes, and systolic blood pressure ranging 80-90 mmHg. After considering this may be an atypical presentation of LX, corticosteroids were increased to methylprednisolone 1 mg/kg IV every 6 h. The patient's condition slowly improved and he was discharged on post-bite Day 10. On post-bite Day 24, he had nearly complete resolution of skin findings. CONCLUSIONS: LR envenomation can cause a variety of dermatological and systemic manifestations of toxicity. It is critical for toxicologists to be aware of the variety of presentations and findings to appropriately assess and treat LX.

Outbreak of Severe Hypoglycemia After Ingestion of a Male Enhancement Supplement - Virginia, August-November 2019.

In August 2019, the Virginia Poison Center (VPC) and the Blue Ridge Poison Center (BRPC) were contacted concerning patients experiencing repeated episodes of marked hypoglycemia following ingestion of a male enhancement supplement tablet marketed as "V8" in convenience stores in central Virginia. Over the following 3 months, the Virginia Department of Agriculture and Consumer Services (VDACS) and the Virginia Department of Health (VDH) conducted an investigation and identified 17 patients meeting the case definition (severe hypoglycemia within 48 hours of consuming an over-the-counter male enhancement supplement in a man with no history of use of insulin or other medication used to control blood glucose). Analysis of the V8 tablets revealed that most contained glyburide, a sulfonylurea oral hypoglycemic used in the treatment of diabetes and associated with prolonged hypoglycemia following overdose (1). To stem this outbreak, V8 was removed from stores when found, and public service announcements were released. The public health implications of V8 use include the potential for substantial morbidity from hypoglycemic episodes and the potential for mortality if health care services are not accessed in a timely manner when hypoglycemia occurs. The presence of V8 in the market poses a serious threat to public health because of its potentially life-threatening adverse effects.

Causative Agents in Clinically Significant Methemoglobinemia: A National Poison Data System Study.

BACKGROUND: Recognition of the agents most commonly implicated in causing methemoglobinemia can provide context for making therapeutic decisions and inform the diagnostic process. We evaluated the etiologic agents most commonly implicated in clinically significant methemoglobinemia using data from the National Poison Data System (NPDS). STUDY QUESTION: What are the most frequent etiologic agents associated with clinically significant methemoglobinemia. STUDY DESIGN: This was a retrospective cross-sectional chart review using electronic data from the NPDS. The NPDS database was queried to identify cases from July 1, 2007, to June 30, 2017, that were coded as methylene blue treatment recommended and/or performed. Cases were excluded if the substance(s) have never been known to cause methemoglobin or the substances suggested methylene blue was used adjunctively for refractory shock (eg, calcium channel or beta blocker). Multiple substance exposures were reviewed and substances not known to cause methemoglobinemia were excluded. MEASURES AND OUTCOMES: The primary end point was to summarize the most frequent etiologic agents associated with the administration of methylene blue for clinically significant methemoglobinemia. RESULTS: There were 2563 substances reported in 1209 cases. After excluding coingestants and cases not associated with methemoglobinemia, there were 1236 substances. The top 4 substance categories were benzocaine, phenazopyridine, dapsone, and nitrates/nitrites. CONCLUSIONS: This study reveals the relative contribution of various drugs and chemicals associated with methylene blue administration. Over two-thirds of all cases were associated with benzocaine, phenazopyridine, dapsone, and nitrates/nitrites.

Public Health Response to Imported Mumps Cases-Fort Campbell, Kentucky, 2018.

Mumps is an acute viral disease caused by a paramyxovirus that presents with fever and swelling of one or more of the salivary glands. Although not generally considered a disease of military importance, mumps has been associated with outbreaks among young adults in close living quarters, potentially placing Soldiers at risk for transmission of mumps when living in congregated settings. This article reports a recent public health response to 3 imported mumps cases occurring at Fort Campbell, Kentucky, that resulted in a contact investigation for 109 close contacts across varied settings. No secondary mumps cases were identified. This report highlights the need for continuous preparation for public health emergency response, and the need to develop and maintain strong working relationships with local civilian public health assets, as well as with installation organizations, such as schools, child care centers, and public affairs resources.

Animal Derived Thiol Induced Work Exacerbated Asthma: A Brief Case Report of a Unique Workplace Hazard.

A 33 year old female healthcare worker with a history of cough variant asthma presented with 2 weeks of dyspnea and cough that she believed to be due to recurring exposure to skunk spray in her work environment. The employee was working in a temporary structure outside the primary hospital campus. During the preceding 2 weeks, at least one striped skunk was observed multiple times by staff members to be crawling under the structure. The employee's symptoms were not initially considered serious by her supervisors who felt that the appreciable "skunk smell" was merely a nuisance odor. Repeated pre- and postexposure spirometry noted a 350 mL and 11% reduction in forced expiratory volume at one second (FEV1). A review of organic chemistry literature found that 2 thiols, also known as mercaptans, produced in striped skunk spray are structurally related to 1-butanethiol, a chemical workplace hazard and known respiratory irritant with established occupational exposure limits. The observation of the chemical similarities between these skunk-derived thiols and workplace thiols was the key factor in getting the employee temporarily removed from a hazardous, albeit unique, working environment.

Sandfly fever in Afghanistan-a sometimes overlooked disease of military importance: a case series and review of the literature.

Sandfly fever, sometimes known as pappataci fever or Phlebotomus fever, is a vector transmitted viral illness with a history of affecting naïve military formations that travel through or fight in areas in which the infection is endemic. We present a series of 4 hospitalized cases of sandfly fever (2 presumptive, 2 laboratory confirmed) that were admitted to a Role 3 hospital in Afghanistan for evaluation and treatment following medical evacuation from a forward area for marked fevers and malaise. Laboratory evaluation of these cases was significant for leukopenia and thrombocytopenia, consistent with historical descriptions of sandfly fever. In the correct geographic and clinical setting, the finding of mild leukopenia among a cluster of febrile patients should prompt the clinician to at least consider a diagnosis of sandfly fever. A cluster investigation conducted by preventive medicine personnel identified numerous other presumed cases of sandfly fever in this forward special operations camp. Response efforts emphasized enforcement of standard vector-borne disease control measures by operational leadership in order to limit effect on tactical operations. We review historical instances of sandfly fever affecting military operations, and present a review of clinical presentation, transmission, management, and prevention.

Severe Systemic Lead Toxicity Resulting From Extra-Articular Retained Shrapnel Presenting as Jaundice and Hepatitis: A Case Report and Review of the Literature.

INTRODUCTION: Despite greater than 60,000 nonfatal firearm injuries per year in the United States, retained shrapnel is a relatively rare cause of systemic lead toxicity with less than 100 cases reported in the medical literature since 1867. While intra-articular retained shrapnel as a cause of lead toxicity is well-described, extra-articular fragments are less well known to cause symptomatic disease. CASE REPORT: A 31-year-old man initially presented with abdominal pain, constipation, jaundice, and elevated liver transaminases approximately 3 weeks after suffering a left lower extremity injury during athletic activity. The patient was found to have steatohepatitis after extensive inpatient and outpatient gastroenterological workup to include upper and lower endoscopy, liver ultrasound, and biopsy of the liver to confirm the diagnosis. Imaging was incidentally notable for retained gunshot in the left flank and large shell fragment containing seroma in the left thigh. The patient was initially discharged with improved pain, but later presented to a primary care clinic with weight loss and continued pain. This was followed by a subsequent progression to diffuse weakness, ultimately resulting in an inability to ambulate. The patient was readmitted to a tertiary care medical center, 3 months after the initial presentation. Physical exam was then notable for 70-lb weight loss from initial admission and diffuse peripheral weakness with global muscle atrophy. Following a broad differential workup, he was found to have a blood lead level of 129 µg/dL, and hemoglobin of 7.7 g/dL with basophilic stippling on peripheral smear. The patient was transferred to the intensive care unit for chelation therapy with dimercaprol and calcium ethylenediaminetetraacetic acid. Lead levels initially decreased, but rose when patient was transitioned to oral therapy with succimer. Surgery was consulted for removal of multiple retained fragments, which were analyzed by the Joint Pathology Center and found to contain lead. The patient's motor function gradually improved on oral chelation and he was discharged to a subacute rehabilitation facility. CONCLUSION: This complex case describes a rare cause for a relatively common clinical presentation, jaundice and hepatitis, and reinforces the importance of longitudinal follow up and reassessment of a patient with an unknown illness and worsening clinical condition. Diagnosis of systemic lead toxicity is challenging because of its protean clinical manifestations, and relative rarity with the advent of strict environmental lead controls and decrease in lead-based paint and industrial products. Furthermore, extra-articular lead remains a rare cause of systemic toxicity, and the surgical standard of care has been to not remove these fragments in gunshot victims. This case adds to a small amount of evidence that lead screening may be of value in selected patients with extra-articular retained shrapnel, especially those with seroma and osteophyte formation in the wound.

The Relationship Between Enlistment Body Mass Index and the Development of Obstructive Sleep Apnea in the U.S. Military.

BACKGROUND: The incidence of obstructive sleep apnea (OSA) in the military has risen dramatically. OSA is considered "service connected" and compensable by the Veterans Administration. The association between body mass index (BMI) (kg/m(2)) measured at initial enlistment and development of OSA has yet to be assessed. METHODS: Data were obtained from the Defense Medical Surveillance System, the Armed Forces Health Surveillance Center, U.S. Department of Defense, Silver Spring, Maryland (inclusive dates:1993-2012; release date: December 2013). A study population of 550,000 randomly-selected active duty enlisted personnel was followed retrospectively from January 1, 2008, through December 31, 2012, or until diagnosis with OSA, separation from the military, or death occurred. The main exposure of interest was BMI recorded at time of enlistment. RESULTS: Adjusted hazard ratios for enlistment BMI were calculated using BMI of 23 to 23.9 as reference. Exponentially increasing risk for OSA was observed as BMI increased. The heaviest individuals (BMI > 35) were at the highest risk (hazard ratio: 3.93; 95% confidence interval [CI]: 3.35-4.62) for developing OSA. CONCLUSION: Enlistment BMI's role in developing OSA may be valuable in designing screening tools and preventive interventions in higher-risk groups, as well as prompt further consideration in the realm of military enlistment policy.