Mandated checkups, knowledge of own health status, and chronic care utilization: The effect of HIV medical evaluation mandates on healthcare quality and expenditure in a US-single payer system.

In an effort to improve military readiness, in 2014 the US Air Force reduced the frequency of mandated HIV medical evaluation visits from every 6 months to every 12 months. We employ this natural experiment using data for 2676 active-duty Military Health System beneficiaries living with HIV with a difference-in-differences empirical strategy using the Army, Navy, and Marines as a control group to estimate the causal effect of reducing the frequency of mandated evaluation visits on the quality and cost of medical care for active-duty military members living with HIV. We find that reducing the frequency of mandated HIV medical evaluation visits reduced the likelihood of regular HIV visits by 23 percentage points but did not affect the likelihood of receiving other preventive care, adhering to HIV therapy, or maintaining viral testing and suppression. The study finds evidence that the recommended level of regular HIV visits may be higher than necessary. The reduction in regular HIV visits was not associated with a similar reduction in the studied quality of care measures, therefore, the effect of alleviating the mandate was overall positive in terms of reducing healthcare utilization without adversely affecting preventive care, HIV therapy, or viral testing and suppression.

Antiretroviral Therapy and Viral Suppression Among Active Duty Service Members with Incident HIV Infection - United States, January 2012-June 2018.

Human immunodeficiency virus (HIV) infection is a deployment-limiting medical condition for U.S. armed forces in the Department of Defense (DoD) (1). HIV management using contemporary antiretroviral therapy (ART) regimens permits effective suppression of viremia among persons in clinical care. Although service members with HIV infection can remain in military service, treatment outcomes have not been fully described. Data from the Defense Medical Surveillance System (DMSS) were analyzed to estimate ART use and viral suppression among DoD service members with diagnosed HIV infection during January 2012-June 2018 (2). Among 1,050 service members newly diagnosed with HIV infection during January 1, 2012-December 31, 2017, 89.4% received ART within 6 months of HIV diagnosis, 95.4% within 12 months, and 98.7% by the end of the surveillance period on June 30, 2018. Analyses determined that, among 793 persons who initiated ART and remained in military service for ≥1 year, 93.8% received continuous ART, 99.0% achieved viral suppression within 1 year after ART initiation, and 96.8% were virally suppressed at receipt of their last viral load test. The DoD model of HIV care demonstrates that service members with HIV infection who remain in care receive timely ART and can achieve both early and sustained viral suppression.

Analysis of Serial Isolates of mcr-1-Positive Escherichia coli Reveals a Highly Active ISApl1 Transposon.

The emergence of a transferable colistin resistance gene (mcr-1) is of global concern. The insertion sequence ISApl1 is a key component in the mobilization of this gene, but its role remains poorly understood. Six Escherichia coli isolates were cultured from the same patient over the course of 1 month in Germany and the United States after a brief hospitalization in Bahrain for an unconnected illness. Four carried mcr-1 as determined by real-time PCR, but two were negative. Two additional mcr-1-negative E. coli isolates were collected during follow-up surveillance 9 months later. All isolates were analyzed by whole-genome sequencing (WGS). WGS revealed that the six initial isolates were composed of two distinct strains: an initial ST-617 E. coli strain harboring mcr-1 and a second, unrelated, mcr-1-negative ST-32 E. coli strain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but the mcr-1-negative ST-32 strain was still present. mcr-1 was associated with a single copy of ISApl1, located on a 64.5-kb IncI2 plasmid that shared >95% homology with other mcr-1 IncI2 plasmids. ISApl1 copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but ISApl1 movement was independent of mcr-1 Some movement was accompanied by gene disruption, including the loss of genes encoding proteins involved in stress responses, arginine catabolism, and l-arabinose utilization. These data represent the first comprehensive analysis of ISApl1 movement in serial clinical isolates and reveal that, under certain conditions, ISApl1 is a highly active IS element whose movement may be detrimental to the host cell.

Viral Hepatitis C-Related Care in Active Duty and Reserve Service Members: A Retrospective Review.

INTRODUCTION: Hepatitis C Virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma, and universal screening of all adults is recommended. Treatment with new direct antiviral agents are well tolerated and highly effective and decrease morbidity and mortality from HCV. The timely treatment of active-duty Service members (SMs) is essential to prevent complications of HCV and to ensure medical readiness and safety of the Department of Defense blood supply. We performed a retrospective review of the quality of care of Navy Active Duty (AD) and reserve SMs diagnosed with HCV to assess rates of successful treatment and compliance with national guideline recommendations and identify potential challenges to receiving curative HCV therapy. MATERIALS AND METHODS: A retrospective chart review was completed on the health records of 54 AD and reserve US Navy SMs diagnosed with HCV. The records were reviewed for timeliness of subspecialty evaluation, achievement of sustained virologic response (SVR), and documentation of the completion of HCV-associated recommendations from national organizations and guidelines. Challenges and barriers to care were identified. RESULTS: Ninety-eight percent of AD and reserve Navy SMs diagnosed with HCV were prescribed treatment, 81% achieved an SVR after completing initial treatment, which reached 92% after initial nonresponders underwent a second round of treatment. Fifty percent of SMs experienced a delay in care due mostly to military-related obligations and patient noncompliance or both. There was a small number of delays in care as a result of prolonged notification of results and referral time. CONCLUSION: As HCV screening recommendations expand to include all adults, more HCV infections will be identified in both the active and reserve components. Modern HCV therapies are both relatively short in duration as well as curative, allowing for the restoration of medical readiness and military service retention. Despite these advantages, we identified challenges of effecting HCV cures in a mobile military population. We recommend centralized compliance monitoring of not only HCV force screening but also HCV treatment to ensure maximized military medical readiness.

Practice guidelines for the diagnosis and management of patients with Q fever by the Armed Forces Infectious Diseases Society.

This issue in the series Current Topics in Military Tropical Medicine focuses on Q Fever. Q fever is a zoonotic infection caused by the bacterium Coxiella burnetii. Over 150 confirmed cases have occurred among U.S. military personnel deployed to Iraq since 2007. Acute Q fever is underdiagnosed because of a myriad of possible clinical presentations but typically presents as a flu-like illness. The most common chronic manifestation is endocarditis. Most providers are not familiar with the diagnosis, treatment, or appropriate follow-up of this disease. In order to facilitate the care of patients infected with C. burnetii, the Armed Forces Infectious Diseases Society convened a panel of experts in the field to develop practical guidelines for those caring for infected patients. The recommendations and rationale are reviewed in this article.

Diagnosis of hepatitis C infection and cascade of care in the active component, U.S. Armed Forces, 2020.

Hepatitis C virus (HCV) infection rates are rising in the U.S. despite widely available tools to identify and effectively treat nearly all of these cases. This cross-sectional study aimed to use laboratory data to evaluate the prevalence of HCV diagnoses among active component U.S. military service members, describe the characteristics of those diagnosed with HCV, and evaluate the adherence of their care to current standards of practice. All service members in the active component U.S. military between 1 January and 31 December 2020 were included in the study population. The primary outcome was an HCV diagnosis at any time during military service, with secondary outcomes of HCV treatment and sustained virologic response (SVR). The initial case-finding algorithm used laboratory data to identify HCV patients seen in infectious disease and gastrointestinal disease clinics in military treatment facilities (MTFs) (direct care); this was supplemented with additional data to assess and correct for undercounting from cases occurring outside MTFs (purchased care). Thirty active component service members in 2020 had been diagnosed with HCV infection during their military service via direct care, or an estimate of 68 cases after correcting for additional cases from purchased care; this number represents only 12% of the expected number of infections based on previous studies. Of the 30 cases treated via direct care, 28 (93%) received HCV treatment, with 27 of those 28 (96%) achieving SVR. Changes to HCV screening policy for military accessions should be considered in order to effectively identify and treat asymptomatic HCV infections that would otherwise go undetected.

Airway management of tetanus after the Haitian earthquake: new aspects of old observations.

Two men developed severe tetanus after the 2010 Haitian earthquake. They were admitted to the United States Naval Ship Comfort, a hospital ship sent to provide humanitarian relief. Severe masseter and intercostal muscle spasm impaired airway access and ventilation. Propofol and sevoflurane relieved the tetany, allowing airway control and ventilation without intubation or neuromuscular blocking drugs during wound debridement. Presynaptic impairment of inhibitory neurotransmitter release by tetanospasmin toxin is countered by enhancement of spinal cord postsynaptic inhibitory receptor activity by general anesthetics. Avoidance of tracheal intubation and mechanical ventilation during anesthesia may be desirable in the settings of limited resources in which tetanus usually presents.

Practicing internal medicine onboard the USNS COMFORT in the aftermath of the Haitian earthquake.

On 12 January 2010, a 7.0-magnitude earthquake devastated the island nation of Haiti, leading to the world's largest humanitarian effort in over 6 decades. The catastrophe caused massive destruction of homes and buildings and overwhelmed the Haitian health care system. The United States responded immediately with a massive relief effort, sending U.S. military forces and civilian volunteers to Haiti's aid and providing a tertiary care medical center aboard the USNS COMFORT hospital ship. The COMFORT offered sophisticated medical care to a geographically isolated population and helped to transfer resource-intensive patients from other treatment facilities. Working collaboratively with the surgical staff, ancillary services, and nursing staff, internists aboard the COMFORT were integral to supporting the mission of the hospital ship and provided high-level care to the casualties. This article provides the perspective of the U.S. Navy internists who participated in the initial response to the Haitian earthquake disaster onboard the COMFORT.

Acclimation temperature affects the metabolic response of amphibian skeletal muscle to insulin.

Frog skeletal muscle mainly utilizes the substrates glucose and lactate for energy metabolism. The goal of this study was to determine the effect of insulin on the uptake and metabolic fate of lactate and glucose at rest in skeletal muscle of the American bullfrog, Lithobates catesbeiana, under varying temperature regimens. We hypothesize that lactate and glucose metabolic pathways will respond differently to the presence of insulin in cold versus warm acclimated frog tissues, suggesting an interaction between temperature and metabolism under varying environmental conditions. We employed radiolabeled tracer techniques to measure in vitro uptake, oxidation, and incorporation of glucose and lactate into glycogen by isolated muscles from bullfrogs acclimated to 5 °C (cold) or 25 °C (warm). Isolated bundles from Sartorius muscles were incubated at 5 °C, 15 °C, or 25 °C, and in the presence and absence of 0.05 IU/mL bovine insulin. Insulin treatment in the warm acclimated and incubated frogs resulted in an increase in glucose incorporation into glycogen, and an increase in intracellular [glucose] of 0.5 µmol/g (P<0.05). Under the same conditions lactate incorporation into glycogen was reduced (P<0.05) in insulin-treated muscle. When compared to the warm treatment group, cold acclimation and incubation resulted in increased rates of glucose oxidation and glycogen synthesis, and a reduction in free intracellular glucose levels (P<0.05). When muscles from either acclimation group were incubated at an intermediate temperature of 15 °C, insulin's effect on substrate metabolism was attenuated or even reversed. Therefore, a significant interaction between insulin and acclimation condition in controlling skeletal muscle metabolism appears to exist. Our findings further suggest that one of insulin's actions in frog muscle is to increase glucose incorporation into glycogen, and to reduce reliance on lactate as the primary metabolic fuel.

Mycobacterium mageritense infection following mastectomy and breast reconstruction requiring triple antibiotic therapy and surgical debridement.

A 40-year-old woman was referred to infectious disease specialists for a Mycobacterium mageritense skin infection following mastectomy and bilateral reconstruction with deep inferior epigastric perforator flap. Her case demonstrates the difficulty in treating non-tuberculosis mycobacterial infections, especially the rarely seen species. She failed to respond to dual antibiotic therapy containing imipenem-cilastin despite reported sensitivity. Additionally, her course was complicated by intolerance to various regimens, including gastrointestinal distress, a drug rash with eosinophilia and systemic symptoms, and tendinopathy. With few published data, no treatment guidelines, and limited medications from which to choose for M. mageritense, her treatment posed a challenge. She ultimately required aggressive surgical intervention and a triple therapy antibiotic regimen. The duration of our patient's treatment and the extent of her complications suggest a potential need for early surgical intervention in postsurgical wounds infected with M. mageritense that do not respond to conventional treatment.

Treatment for Severe Coronavirus Disease 2019 With the Seraph-100 Microbind Affinity Blood Filter.

To determine whether Seraph-100 (Exthera Medical Corporation, Martinez, CA) treatment provides clinical benefit for severe coronavirus disease 2019 cases that require mechanical ventilation and vasopressor support. DATA SOURCES: The first two patients in the United States treated with the novel Seraph-100 device. These cases were reviewed by the Food and Drug Administration prior to granting an emergency use authorization for treatment of coronavirus disease 2019. STUDY SELECTION: Case series. DATA EXTRACTION: Vasopressor dose, mean arterial pressure, temperature, interleukin-6, C-reactive protein, and other biomarker levels were documented both before and after Seraph-100 treatments. DATA SYNTHESIS: Vasopressor dose, temperature, interleukin-6, and C-reactive protein levels declined after Seraph-100 treatments. Severe acute respiratory syndrome coronavirus 2 viremia was confirmed in the one patient tested and cleared by the completion of treatments. CONCLUSIONS: Seraph-100 use may improve hemodynamic stability in coronavirus disease 2019 cases requiring mechanical ventilation and vasopressor support. These findings warrant future study of a larger cohort with the addition of mortality and total hospital day outcomes.

Does prior dengue virus exposure worsen clinical outcomes of Zika virus infection? A systematic review, pooled analysis and lessons learned.

Zika virus (ZIKV) recently caused a pandemic complicated by Guillain-Barre syndrome (GBS) and birth defects. ZIKV is structurally similar to the dengue viruses (DENV) and in vitro studies suggest antibody dependent enhancement occurs in ZIKV infections preceded by DENV; however, the clinical significance of this remains unclear. We undertook a PRISMA-adherent systematic review of all current human and non-human primate (NHP) data to determine if prior infection with DENV, compared to DENV-naïve hosts, is associated with a greater risk of ZIKV clinical complications or greater ZIKV peak viremia in vivo. We identified 1146 studies in MEDLINE, EMBASE and the grey literature, of which five studies were eligible. One human study indicated no increase in the risk of GBS in ZIKV infections with prior DENV exposure. Two additional human studies showed a small increase in ZIKV viremia in those with prior DENV exposure; however, this was not statistically significant nor was it associated with an increase in clinical severity or adverse pregnancy outcomes. While no meta-analysis was possible using human data, a pooled analysis of the two NHP studies leveraging extended data provided only weak evidence of a 0.39 log10 GE/mL rise in ZIKV viremia in DENV experienced rhesus macaques compared to those with no DENV exposure (p = 0.22). Using a customized quality grading criteria, we further show that no existing published human studies have offered high quality measurement of both acute ZIKV and antecedent DENV infections. In conclusion, limited human and NHP studies indicate a small and non-statistically significant increase in ZIKV viremia in DENV-experienced versus DENV-naïve hosts; however, there is no evidence that even a possible small increase in ZIKV viremia would correlate with a change in ZIKV clinical phenotype. More data derived from larger sample sizes and improved sero-assays are needed to resolve this question, which has major relevance for clinical prognosis and vaccine design.

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia.

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here, we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force, and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation.

Contributions to elevated metabolism during recovery: dissecting the excess postexercise oxygen consumption (EPOC) in the desert iguana (Dipsosaurus dorsalis).

The excess postexercise oxygen consumption (EPOC), a measure of recovery costs, is known to be large in ectothermic vertebrates such as the desert iguana (Dipsosaurus dorsalis), especially after vigorous activity. To analyze the cause of these large recovery costs in a terrestrial ectotherm, Dipsosaurus were run for 15 s at maximal-intensity (distance 35.0+/-1.9 m; 2.33+/-0.13 m s(-1)) while O(2) uptake was monitored via open-flow respirometry. Muscle metabolites (adenylates, phosphocreatine, and lactate) were measured at rest and after 0, 3, 10, and 60 min of recovery. Cardiac and ventilatory activity during rest and recovery were measured, as were whole-body lactate and blood lactate, which were used to estimate total muscle activity. This vigorous activity was supported primarily by glycolysis (65%) and phosphocreatine hydrolysis (29%), with only a small contribution from aerobic metabolism (2.5%). Aerobic recovery lasted 43.8+/-4.6 min, and EPOC measured 0.166+/-0.025 mL O(2) g(-1). This was a large proportion (98%) of the total suprabasal metabolic cost of the activity to the animal. The various contributions to EPOC after this short but vigorous activity were quantified, and a majority of EPOC was accounted for. The two primary causes of EPOC were phosphocreatine repletion (32%-50%) and lactate glycogenesis (30%-47%). Four other components played smaller roles: ATP repletion (8%-13%), elevated ventilatory activity (2%), elevated cardiac activity (2%), and oxygen store resaturation (1%).

Metabolic support of moderate activity differs from patterns seen after extreme behavior in the desert iguana Dipsosaurus dorsalis.

This study examined glucose and lactate metabolism in an iguanid lizard, Dipsosaurus dorsalis, during rest and after activity patterned on field behavior (15 s of running at 1 m/s). Metabolite oxidation and incorporation into glycogen by the whole animal, the liver, and oxidative and glycolytic muscle fibers were measured using (14)C- and (13)C-labeled compounds. Results showed that lactate metabolism is more responsive to changes that occurred between rest and recovery, whereas glucose appears to play a more steady state role. After activity, lactate oxidation produced 57 times as much ATP during 1 h of recovery than did glucose oxidation. However, lactate oxidation rates were elevated for only 30 min after activity, while glucose oxidation remained elevated beyond 1 h. Lactate was the primary source for glycogen synthesis during recovery, and glucose was the main glycogenic substrate during rest. This study supports previous research showing that brief activity in D. dorsalis is primarily supported by glycolysis and phosphocreatine breakdown, but it also suggests that there may be less of a reliance on glycolysis and a greater reliance on phosphocreatine than previously shown. The findings presented here indicate that the metabolic consequences of the behaviorally relevant activity studied are less severe than has been suggested by studies using more extreme activity patterns.

Intermittent locomotor activity that increases endurance also increases metabolic costs in the desert Iguana (Dipsosaurus dorsalis).

Intermittent activity, alternating bouts of activity and rest, can extend endurance relative to continuous locomotion. Utilizing a rapid fatiguing activity intensity (1.08 m s(-1)), Dipsosaurus dorsalis (n = 14) ran repeated bouts of varying durations (5, 15, or 30 s) interspersed with variable pause periods (100%, 200%, 400%, or 800% of the activity period) until exhausted. Total distance ran increased relative to continuous locomotion. The largest increases were seen when activity periods were limited to 5 s and pause periods were extended from 5 s to 20 s to 40 s (55, 118, and 193 m, respectively). To analyze these increases further, O(2) consumption was measured for six bouts of 5-s activity separated by either 5, 20, or 40 s (n = 8). The sum of elevated O(2) consumption during activity, pauses, and recovery increased significantly from 0.08 to 0.09 and 0.12 mL O(2) g(-1) as pause duration increased, primarily due to greater O(2) consumption during longer pause intervals. Postexercise recovery metabolism was a large cost (>57% of total) but did not differ among treatments. Overall, 40-s pauses were most expensive (absolutely and per unit distance) but provided the greatest endurance, likely due to further repletion of metabolites or removal of end products during the longer pause. In contrast, the shortest pause period was most economical but exhausted the animal most rapidly. Thus, a pattern of intermittent activity utilized by an animal may have energetic advantages that sometimes may be offset by behavioral costs associated with fatigue.

The effect of oxygen and adenosine on lizard thermoregulation.

A regulated decrease in internal body temperature (Tb) appears to play a protective role against metabolic disruptions such as exposure to ambient hypoxia. This study examined the possibility that Tb depression is initiated when low internal oxygen levels trigger the release of adenosine, a neural modulator known to influence thermoregulation. We measured selected Tb of Anolis sagrei in a thermal gradient under varied ambient oxygen conditions and following the administration of the adenosine receptor antagonist 8-cyclopentyltheophylline (CPT). The average decrease in Tb observed following exposure to hypoxia (<10% O2) and following exhaustive exercise were 5 degrees and 3 degrees C, respectively, suggesting a role of oxygen availability on initiation of regulated hypothermia. When A. sagrei were run to exhaustion and recovered in hyperoxic (>95% O2) conditions, exercise-induced Tb depression was abolished. Administration of CPT similarly abolished decreased Tb due to both exercise and hypoxia. Trials using Dipsosaurus dorsalis indicate that elevated ambient oxygen during exercise does not influence blood pH or lactate accumulation, suggesting that these factors do not initiate changes in thermoregulatory setpoint following exhaustive exercise. We suggest that when oxygen is limiting, a decrease in arterial oxygen may trigger the release of adenosine, thereby altering the thermoregulatory setpoint.

Campylobacter fetus bacteremia in an immunocompetent traveler.

Campylobacter fetus bacteremia is a rare human infection that occurs almost exclusively in the setting of advanced age, immunosuppression, human immunodeficiency virus infection, alcoholism, or recent gastrointestinal surgery. This report of C. fetus bacteremia in a 39-year-old immunocompetent traveler who ate raw beef identifies C. fetus as a potential emerging pathogen in normal hosts.