Contingency management with stepped care for unhealthy alcohol use among individuals with HIV: Protocol for a randomized controlled trial.

BACKGROUND: Although unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial. METHODS: PWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described. CONCLUSIONS: The FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH. CLINICALTRIALS: gov identifier: NCT03089320.

Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis.

OBJECTIVE: Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS: We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. RESULTS: Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSION: Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Is Bone Loss or Devascularization Associated With Recurrence of Osteomyelitis in Wartime Open Tibia Fractures?

BACKGROUND: During recent wars, 26% of combat casualties experienced open fractures and these injuries frequently are complicated by infections, including osteomyelitis. Risk factors for the development of osteomyelitis with combat-related open tibia fractures have been examined, but less information is known about recurrence of this infection, which may result in additional hospitalizations and surgical procedures. QUESTIONS/PURPOSES: (1) What is the risk of osteomyelitis recurrence after wartime open tibia fractures and how does the microbiology compare with initial infections? (2) What factors are associated with osteomyelitis recurrence among patients with open tibia fractures? (3) What clinical characteristics and management approaches are associated with definite/probable osteomyelitis as opposed to possible osteomyelitis and what was the microbiology of these infections? METHODS: A survey of US military personnel injured during deployment between March 2003 and December 2009 identified 215 patients with open tibia fractures, of whom 130 patients developed osteomyelitis and were examined in a retrospective analysis. No patients with bilateral osteomyelitis were included. Twenty-five patients meeting osteomyelitis diagnostic criteria were classified as definite/probable (positive bone culture, direct evidence of infection, or symptoms with culture and/or radiographic evidence) and 105 were classified as possible (bone contamination, organism growth in deep wound tissue, and evidence of local/systemic inflammation). Patients diagnosed with osteomyelitis were treated with débridement and irrigation as well as intravenous antibiotics. Fixation hardware was retained until fracture union, when possible. Osteomyelitis recurrence was defined as a subsequent osteomyelitis diagnosis at the original site ≥ 30 days after completion of initial treatment. This followup period was chosen based on the definition of recurrence so as to include as many patients as possible for analysis. Factors associated with osteomyelitis recurrence were assessed using univariate analysis in a subset of the population with ≥ 30 days of followup. Patients who had an amputation at or proximal to the knee after the initial osteomyelitis were not included in the recurrence assessment. RESULTS: Of 112 patients meeting the criteria for assessment of recurrence, 31 (28%) developed an osteomyelitis recurrence, of whom seven of 25 (28%) had definite/probable and 24 of 87 (28%) had possible classifications for their initial osteomyelitis diagnosis. Risk of osteomyelitis recurrence was associated with missing or devascularized bone (recurrence, 14 of 31 [47%]; nonrecurrence, 22 of 81 [28%]; hazard ratio [HR], 3.94; 1.12-13.81; p = 0.032) and receipt of antibiotics for 22-56 days (recurrence, 20 of 31 [65%]; nonrecurrence: 37 of 81 [46%]; HR, 2.81; 1.05-7.49; p = 0.039). Compared with possible osteomyelitis, definite/probable osteomyelitis was associated with localized swelling at the bone site (13 of 25 [52%] versus 28 of 105 [27%]; risk ratio [RR], 1.95 [1.19-3.19]; p = 0.008) and less extensive skin and soft tissue injury at the time of trauma (9 of 22 [41%; three definite/probably patients missing data] versus 13 of 104 [13%; one possible patient missing data]; RR, 3.27 [1.60-6.69]; p = 0.001). Most osteomyelitis infections were polymicrobial (14 of 23 [61%; two patients with missing data] for definite/probable patients and 62 of 105 [59%] for possible patients; RR, 1.03 [0.72-1.48]; p = 0.870). More of the definite/probable patients received vancomycin (64%) compared with the possible patients (41%; p = 0.046), and the duration of polymyxin use was longer (median, 38 days versus 16 days, p = 0.018). Time to definitive fracture fixation was not different between the groups. CONCLUSIONS: Recurrent osteomyelitis after open tibia fractures is common. In a univariate model, patients with an intermediate amount of bone loss and those treated with antibiotics for 22 to 56 days were more likely to experience osteomyelitis recurrence. Because only univariate analysis was possible, these findings should be considered preliminary. Osteomyelitis recurrence rates were similar, regardless of initial osteomyelitis classification, indicating that diagnoses of possible osteomyelitis should be treated aggressively. LEVEL OF EVIDENCE: Level III, therapeutic study.

Osteomyelitis Risk Factors Related to Combat Trauma Open Femur Fractures: A Case-Control Analysis.

OBJECTIVES: To identify the risk factors for osteomyelitis development in US military personnel with combat-related, open femur fractures? DESIGN: Retrospective observational case-control study. SETTING: US military regional hospital in Germany and tertiary care hospitals in United States (2003-2009). PATIENTS/PARTICIPANTS: One hundred three patients with open femur fractures who met diagnostic osteomyelitis criteria (medical record review verification) were classified as cases. Sixty-four patients with open femur fractures who did not meet osteomyelitis diagnostic criteria were included as controls. MAIN OUTCOME MEASUREMENTS: The main outcome measurements were multivariable odds ratios (ORs) and 95% confidence interval (CI). RESULTS: Among patients with surgical implants, osteomyelitis cases had significantly longer time to definitive orthopaedic surgery compared with controls (median: 21 vs. 13 days). Independent predictors for osteomyelitis risk were Gustilo-Anderson classification (transfemoral amputation OR: 19.3; CI: 3.0-123.0) and Orthopaedic Trauma Association Open Fracture Classification for muscle loss (OR: 5.7; CI: 1.3-25.1) and dead muscle (OR: 32.9; CI: 5.4-199.1). Being injured between 2003 and 2006, antibiotic bead use, and foreign body plus implant(s) at fracture site were also risk factors. CONCLUSIONS: Patients with open femur fractures resulting in significant muscle damage have the highest osteomyelitis risk. Foreign body contamination was only significant when an implant was present. Increased risk with antibiotic bead use is likely a surrogate for clinical suspicion of contamination with complex wounds. The timeframe association is likely due to changing trauma system patterns around 2006-2007 (eg, increased negative pressure wound therapy, reduced high-pressure irrigation, decreased crystalloid use, and delayed definitive internal fixations). LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Early Infections Complicating the Care of Combat Casualties from Iraq and Afghanistan.

BACKGROUND: During the conflicts in Iraq and Afghanistan, more than 52,000 U.S. military members were wounded in action. The battlefield mortality rate was lower than in past conflicts, however, those surviving often had complex soft tissue and bone injuries requiring multiple surgeries. This report describes the rates, types, and risks of infections complicating the care of combat casualties. PATIENTS AND METHODS: Infection and microbiology data obtained from the Trauma Infectious Disease Outcomes Study (TIDOS), a prospective observational study of infections complicating deployment-related injuries, were used to determine the proportion of infection, types, and associated organisms. Injury and surgical information were collected from the Department of Defense Trauma Registry. Multivariable Cox proportional hazards and logistic regression models were used to evaluate potential factors associated with infection. RESULTS: From 2009-2012, 1,807 combat casualties were evacuated to U.S. TIDOS-participating hospitals. Among the 1,807 patients, the proportion of overall infections from time of injury through initial U.S. hospitalization was 34% with half being skin, soft tissue, or bone infections. Infected wounds most commonly grew Enterococcus faecium, Pseudomonas aeruginosa, Acinetobacter spp. or Escherichia coli. In the multivariable model, amputation, blood transfusions, intensive care unit admission, injury severity scores, mechanical ventilation, and mechanism of injury were associated with risk of infection. CONCLUSIONS: One-third of combat casualties from Iraq and Afghanistan develop infections during their initial hospitalization. Amputations, blood transfusions, and overall injury severity are associated with risk of infection, whereas more easily modifiable factors such as early operative intervention or antibiotic administration are not.

Epidemiology of Trauma-Related Infections among a Combat Casualty Cohort after Initial Hospitalization: The Trauma Infectious Disease Outcomes Study.

BACKGROUND: The Trauma Infectious Disease Outcomes Study (TIDOS) cohort follows military personnel with deployment-related injuries in order to evaluate short- and long-term infectious complications. High rates of infectious complications have been observed in more than 30% of injured patients during initial hospitalization. We present data on infectious complications related to combat trauma after the initial period of hospitalization. PATIENTS AND METHODS: Data related to patient care for military personnel injured during combat operations between June 2009 and May 2012 were collected. Follow-up data were captured from interviews with enrolled participants and review of electronic medical records. RESULTS: Among 1,006 patients enrolled in the TIDOS cohort with follow-up data, 357 (35%) were diagnosed with one or more infection during their initial hospitalization, of whom 160 (45%) developed a trauma-related infection during follow-up (4.2 infections per 10,000 person-days). Patients with three or more infections during the initial hospitalization had a significantly higher rate of infections during the follow-up period compared with those with only one inpatient infection (incidence rate: 6.6 versus 3.1 per 10,000 days; p < 0.0001). There were 657 enrollees who did not have an infection during initial hospitalization, of whom 158 (24%) developed one during follow-up (incidence rate: 1.6 per 10,000 days). Overall, 318 (32%) enrolled patients developed an infection after hospital discharge (562 unique infections) with skin and soft-tissue infections being predominant (66%) followed by osteomyelitis (16%). Sustaining an amputation or open fracture, having an inpatient infection, and use of anti-pseudomonal penicillin (≥7 d) were independently associated with risk of an extremity wound infection during follow-up, whereas shorter hospitalization (15-30 d) was associated with a reduced risk. CONCLUSIONS: Combat-injured patients have a high burden of infectious complications that continue long after the initial period of hospitalization with soft-tissue and osteomyelitis being predominant. Further research on the long-term impact and outcomes of combat-associated infection is needed.

Infectious Complications After Deployment Trauma: Following Wounded US Military Personnel Into Veterans Affairs Care.

Background: Infectious complications related to deployment trauma significantly contribute to the morbidity and mortality of wounded service members. The Trauma Infectious Disease Outcomes Study (TIDOS) collects data on US military personnel injured in Iraq and Afghanistan in an observational cohort study of infectious complications. Patients enrolled in TIDOS may also consent to follow-up through the Department of Veterans Affairs (VA). We present data from the first 337 TIDOS enrollees to receive VA healthcare. Methods: Data were collected from the Department of Defense (DoD) Trauma Registry, TIDOS infectious disease module, DoD and VA electronic medical records, and telephone interview. Cox proportional hazard analysis was performed to identify predictors of post-discharge infections related to deployment trauma. Results: Among the first 337 TIDOS enrollees who entered VA healthcare, 111 (33%) had 244 trauma-related infections during their initial trauma hospitalization (2.1 infections per 100 person-days). Following initial discharge, 127 (38%) enrollees had 239 trauma-related infections (170 during DoD follow-up and 69 during VA time). Skin and soft-tissue infections and osteomyelitis were predominant during and after the initial trauma hospitalization. In a multivariate model, a shorter time to development of a new infection following discharge was independently associated with injury severity score ≥10 and occurrence of ≥1 inpatient infection during initial trauma hospitalization. Conclusions: Incident infections related to deployment trauma continue well after initial hospital discharge and into VA healthcare. Overall, 38% of enrolled patients developed a new trauma-related infection after their initial hospital discharge, with 29% occurring after the patient left military service.

Impact of Operational Theater on Combat and Noncombat Trauma-Related Infections.

The Trauma Infectious Disease Outcomes Study began in June 2009 as combat operations were decreasing in Iraq and increasing in Afghanistan. Our analysis examines the rate of infections of wounded U.S. military personnel from operational theaters in Iraq and Afghanistan admitted to Landstuhl Regional Medical Center between June 2009 and December 2013 and transferred to a participating U.S. hospital. Infection risk factors were examined in a multivariate logistic regression analysis (expressed as odds ratios [OR]; 95% confidence intervals [CI]). The study population includes 524 wounded military personnel from Iraq and 4,766 from Afghanistan. The proportion of patients with at least one infection was 28% and 34% from the Iraq and Afghanistan theaters, respectively. The incidence density rate was 2.0 (per 100 person-days) for Iraq and 2.7 infections for Afghanistan. Independent risk factors included large-volume blood product transfusions (OR: 10.68; CI: 6.73-16.95), high Injury Severity Score (OR: 2.48; CI: 1.81-3.41), and improvised explosive device injury mechanism (OR: 1.84; CI: 1.35-2.49). Operational theater (OR: 1.32; CI: 0.87-1.99) was not a risk factor. The difference in infection rates between operational theaters is primarily a result of increased injury severity in Afghanistan from a higher proportion of blast-related trauma during the study period.

Histopathological techniques for the diagnosis of combat-related invasive fungal wound infections.

BACKGROUND: Effective management of trauma-related invasive fungal wound infections (IFIs) depends on early diagnosis and timely initiation of treatment. We evaluated the utility of routine staining, histochemical stains and frozen section for fungal element identification. METHODS: A total of 383 histopathological specimens collected from 66 combat-injured United States military personnel with IFIs were independently reviewed by two pathologists. Both periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) stains were used on 74 specimens. The performance of the two special stains was compared against the finding of fungal elements via any histopathological method (ie, special stains or hematoxylin and eosin). In addition, the findings from frozen sections were compared against permanent sections. RESULTS: The GMS and PAS results were 84 % concordant (95 % confidence interval: 70 to 97 %). The false negative rate of fungal detection was 15 % for GMS and 44 % for PAS, suggesting that GMS was more sensitive; however, neither stain was statistically significantly superior for identifying fungal elements (p = 0.38). Moreover, 147 specimens had frozen sections performed, of which there was 87 % correlation with permanent sections (60 % sensitivity and 98 % specificity). In 27 permanent sections, corresponding cultures were available for comparison and 85 % concordance in general species identification was reported. CONCLUSIONS: The use of both stains does not have an added benefit for identifying fungal elements. Furthermore, while the high specificity of frozen section may aid in timely IFI diagnoses, it should not be used as a stand-alone method to guide therapy due to its low sensitivity.

Isolation of Rapidly Growing Nontuberculous Mycobacteria in Wounds Following Combat-Related Injury.

OBJECTIVES: Rapidly growing nontuberculous mycobacteria (RGNTM) have yet to be described in combat-related injuries. This study investigates the epidemiology, clinical findings, treatment, and outcomes of RGNTM infections among combat casualties wounded in Afghanistan from 2010 to 2012. METHODS: Patients with RGNTM were identified from the Department of Defense Trauma Registry through the Trauma Infectious Disease Outcomes Study. Trauma history, surgical management, and clinical data were collected. Six isolates from patients requiring antimycobacterial therapy were sequenced. RESULTS: Seventeen cases were identified. Six cases, predominantly associated with Mycobacterium abscessus, required aggressive debridement and a median of 180 days of multidrug antimycobacterial therapy that included clofazimine. M. abscessus isolates expressed the erythromycin resistance methylase (erm(41)) gene for inducible macrolide resistance, yet there were no clinical treatment failures when macrolides were utilized in combination therapy. No clonal similarity between M. abscessus isolates was found. Eleven cases had positive wound cultures, but did not require antimycobacterial therapy. The median duration of time of injury to first detection of a RGNTM was 57 days. CONCLUSIONS: This represents the first report of RGNTM infections in war-wounded patients. RGNTM should be recognized as potential pathogens in grossly infected combat wounds. Surgical debridement and multidrug antimycobacterial therapy, when clinically indicated, was associated with satisfactory clinical outcomes.

MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity.

People with HIV infection are at increased risk for community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs). Lower CD4 T-cell counts, higher peak HIV RNA levels and epidemiological factors may be associated with increased risk but no specific immune defect has been identified. We aimed to determine the immunologic perturbations that predispose HIV-infected people to MRSA SSTIs. Participants with or without HIV infection and with MRSA SSTI, MRSA colonization or negative for MRSA were enrolled. Peripheral blood and skin biopsies from study participants were collected. Flow cytometry, flow cytometry with microscopy, multiplex assays of cell culture supernatants and immunohistochemistry were used to evaluate the nature of the immune defect predisposing HIV-infected people to MRSA infections. We found deficient MRSA-specific IFNγ+ CD4 T-cell responses in HIV-infected people with MRSA SSTIs compared to MRSA-colonized participants and HIV-uninfected participants with MRSA SSTIs. These IFNγ+ CD4 T cells were less polyfunctional in HIV-infected participants with SSTIs compared to those without SSTIs. However, IFNγ responses to cytomegalovirus and Mycobacterium avium antigens and MRSA-specific IL-17 responses by CD4 T cells were intact. Upon stimulation with MRSA, peripheral blood mononuclear cells from HIV-infected participants produced less IL-12 and IL-15, key drivers of IFNγ production. There were no defects in CD8 T-cell responses, monocyte responses, opsonization, or phagocytosis of Staphylococcus aureus. Accumulation of CD3 T cells, CD4 T cells, IL-17+ cells, myeloperoxidase+ neutrophils and macrophage/myeloid cells to the skin lesions were similar between HIV-infected and HIV-uninfected participants based on immunohistochemistry. Together, these results indicate that MRSA-specific IFNγ+ CD4 T-cell responses are essential for the control of initial and recurrent MRSA infections in HIV-infected people.

Multidrug-resistant gram-negative bacilli colonization risk factors among trauma patients.

Prior studies have demonstrated high rates of colonization and infection with multidrug-resistant gram-negative bacilli (MDR-GNB) in injured military personnel. Our analysis shows that injuries inflicted during peak combat periods, massive blood transfusion requirement, and posttrauma cefazolin prophylaxis (additive effect with fluoroquinolones) were risk factors for MDR-GNB colonization.

Epidemiology and antimicrobial susceptibilities of wound isolates of obligate anaerobes from combat casualties.

Data from recent conflicts related to war wounds and obligate anaerobes are limited. We define the epidemiology and antimicrobial susceptibility of obligate anaerobes from Iraq and Afghanistan casualties (6/2009-12/2013), as well as their association with clinical outcomes. Susceptibility against eleven antibiotics (7 classes) was tested. Overall, 59 patients had 119 obligate anaerobes identified (83 were first isolates). Obligate anaerobes were isolated 7-13 days post-injury, primarily from lower extremity wounds (43%), and were largely Bacteroides spp. (42%) and Clostridium spp. (19%). Patients with pelvic wounds were more likely to have Bacteroides spp. and concomitant resistant gram-negative aerobes. Seventy-three percent of isolates were resistant to ≥1 antimicrobials. Bacteroides spp. demonstrated the most resistance (16% of first isolates). Patients with resistant isolates had similar outcomes to those with susceptible strains. Serial recovery of isolates occurred in 15% of patients and was significantly associated with isolation of Bacteroides spp., along with resistant gram-negative aerobes.

Early Complications and Outcomes in Combat Injury-Related Invasive Fungal Wound Infections: A Case-Control Analysis.

OBJECTIVE: Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures before initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. DESIGN: Retrospective review and case-control analysis. SETTING: Military hospitals. PATIENTS/PARTICIPANTS: US military personnel injured during combat operations (2009-2011). The IFI cases were identified based on the presence of recurrent, necrotic extremity wounds with mold growth in culture, and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Amputation revision rate and loss of functional levels. RESULTS: Seventy-one IFI cases (112 fungal-infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (P < 0.001). Additionally, significantly (P < 0.001) higher number of operative procedures and longer duration to initial wound closure were associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% confidence interval, 1.17-2.01). The supplemental matching analysis found similar results. CONCLUSIONS: Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load.

Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between ∼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.

Environmental Factors Related to Fungal Wound Contamination after Combat Trauma in Afghanistan, 2009-2011.

During the recent war in Afghanistan (2001-2014), invasive fungal wound infections (IFIs) among US combat casualties were associated with risk factors related to the mechanism and pattern of injury. Although previous studies recognized that IFI patients primarily sustained injuries in southern Afghanistan, environmental data were not examined. We compared environmental conditions of this region with those of an area in eastern Afghanistan that was not associated with observed IFIs after injury. A larger proportion of personnel injured in the south (61%) grew mold from wound cultures than those injured in the east (20%). In a multivariable analysis, the southern location, characterized by lower elevation, warmer temperatures, and greater isothermality, was independently associated with mold contamination of wounds. These environmental characteristics, along with known risk factors related to injury characteristics, may be useful in modeling the risk for IFIs after traumatic injury in other regions.

Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections.

Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth.

Healthcare-associated pneumonia among U.S. combat casualties, 2009 to 2010.

Although there is literature evaluating infectious complications associated with combat-related injuries from Iraq and Afghanistan, none have evaluated pneumonia specifically. Therefore, we assessed a series of pneumonia cases among wounded military personnel admitted to Landstuhl Regional Medical Center, and then evacuated further to participating U.S. military hospitals. Of the 423 casualties evacuated to the United States, 36 developed pneumonia (8.5%) and 30 of these (83.3%) were ventilator-associated. Restricting to 162 subjects admitted to intensive care, 30 patients had pneumonia (18.5%). The median Injury Severity Score was higher among subjects with pneumonia (23.0 vs. 6.0; p < 0.01). There were 61 first-isolate respiratory specimens recovered from 31 pneumonia subjects, of which 56.1% were gram-negative, 18.2% were gram-positive, and 18.2% were fungal. Staphylococcus aureus and Pseudomonas aeruginosa were most commonly recovered (10.6%, and 9.1%, respectively). Thirteen bacterial isolates (26.5%) were multidrug-resistant. Outcome data were available for 32 patients, of which 26 resolved their infection without progression, 5 resolved after initial progression, and 1 died. Overall, combat-injured casualties suffer a relatively high rate of pneumonia, particularly those requiring mechanical ventilation. Although gram-negative pathogens were common, S. aureus was most frequently isolated. Continued focus on pneumonia prevention strategies is necessary for improving combat care.

A single dose of benzathine penicillin G is as effective as multiple doses of benzathine penicillin G for the treatment of HIV-infected persons with early syphilis.

BACKGROUND: Treatment guidelines recommend the use of a single dose of benzathine penicillin G (BPG) for treating early syphilis in human immunodeficiency virus (HIV)-infected persons. However, data supporting this recommendation are limited. We examined the efficacy of single-dose BPG in the US Military HIV Natural History Study. METHODS: Subjects were included if they met serologic criteria for syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal testing). Response to treatment was assessed at 13 months and was defined by a ≥4-fold decline in NTr titer. Multivariate Cox proportional hazard regression models were utilized to examine factors associated with treatment response. RESULTS: Three hundred fifty subjects (99% male) contributed 478 cases. Three hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year increase; 95% confidence interval [CI], .73-.93) was associated with delayed response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR, 1.94 [95% CI, 1.58-2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase [95% CI, 1.01-1.12]) were associated with a faster response to treatment. Response was not affected by the number of BPG doses received (reference, 1 dose of BPG; HR, 1.11 [95% CI, .89-1.4]). CONCLUSIONS: In this cohort, additional BPG doses did not affect treatment response. Our data support the current recommendations for the use of a single dose of BPG to treat HIV-infected persons with early syphilis.