Antibiotic Practice Patterns for Extremity Wound Infections among Blast-Injured Subjects.

INTRODUCTION: We examined antibiotic management of combat-related extremity wound infections (CEWI) among wounded U.S. military personnel (2009-2012). METHODS: Patients were included if they sustained blast injuries, resulting in ≥1 open extremity wound, were admitted to participating U.S. hospitals, developed a CEWI (osteomyelitis or deep soft-tissue infections) within 30 days post-injury, and received ≥3 days of relevant antibiotic (s) for treatment. RESULTS: Among 267 patients, 133 (50%) had only a CEWI, while 134 (50%) had a CEWI plus concomitant non-extremity infection. In the pre-diagnosis period (4-10 days prior to CEWI diagnosis), 95 (36%) patients started a new antibiotic with 28% of patients receiving ≥2 antibiotics. During CEWI diagnosis week (±3 days of diagnosis), 209 (78%) patients started a new antibiotic (71% with ≥2 antibiotics). In the week following diagnosis (4-10 days after CEWI diagnosis), 121 (45%) patients started a new antibiotic with 39% receiving ≥2 antibiotics. Restricting to ±7 days of CEWI diagnosis, patients commonly received two (35%) or three (27%) antibiotics with frequent combinations involving carbapenem, vancomycin, and fluoroquinolones. CONCLUSIONS: Substantial variation in antibiotic prescribing patterns related to CEWIs warrants development of combat-related clinical practice guidelines beyond infection prevention, to include strategies to reduce the use of unnecessary antibiotics and improve stewardship.

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

OBJECTIVE: To determine risk factors for osteomyelitis in US military personnel with combat-related, extremity long bone (humerus, radius, and ulna) open fractures. DESIGN: Retrospective observational case-control study. SETTING: US military regional hospital in Germany and tertiary care military hospitals in the United States (2003-2009). PATIENTS/PARTICIPANTS: Sixty-four patients with open upper extremity fractures who met diagnostic osteomyelitis criteria (medical record review verification) were classified as cases. Ninety-six patients with open upper extremity fractures who did not meet osteomyelitis diagnostic criteria were included as controls. INTERVENTION: Not applicable. MAIN OUTCOME MEASUREMENTS: Multivariable odds ratios (ORs; 95% confidence interval [CI]). RESULTS: Among patients with surgical implants, osteomyelitis cases had longer time to definitive orthopaedic surgery compared with controls (median: 26 vs. 11 days; P < 0.001); however, there was no significant difference with timing of radiographic union. Being injured between 2003 and 2006, use of antibiotic beads, Gustilo-Anderson [GA] fracture classification (highest with GA-IIIb: [OR: 22.20; CI: 3.60-136.95]), and Orthopaedic Trauma Association Open Fracture Classification skin variable (highest with extensive degloving [OR: 15.61; CI: 3.25-74.86]) were independently associated with osteomyelitis risk. Initial stabilization occurring outside of the combat zone was associated with reduced risk of osteomyelitis. CONCLUSIONS: Open upper extremity fractures with severe soft-tissue damage have the highest risk of developing osteomyelitis. The associations with injuries sustained 2003-2006 and location of initial stabilization are likely from evolving trauma system recommendations and practice patterns during the timeframe. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

Combat-Related Extremity Wounds: Injury Factors Predicting Early Onset Infections.

We examined risk factors for combat-related extremity wound infections (CEWI) among U.S. military patients injured in Iraq and Afghanistan (2009-2012). Patients with ≥1 combat-related, open extremity wound admitted to a participating U.S. hospital (≤7 days postinjury) were retrospectively assessed. The population was classified based upon most severe injury (amputation, open fracture without amputation, or open soft-tissue injury defined as non-fracture/non-amputation wounds). Among 1271 eligible patients, 395 (31%) patients had ≥1 amputation, 457 (36%) had open fractures, and 419 (33%) had open soft-tissue wounds as their most severe injury, respectively. Among patients with traumatic amputations, 100 (47%) developed a CEWI compared to 66 (14%) and 12 (3%) patients with open fractures and open soft-tissue wounds, respectively. In a Cox proportional hazard analysis restricted to CEWIs ≤30 days postinjury among the traumatic amputation and open fracture groups, sustaining an amputation (hazard ratio: 1.79; 95% confidence interval: 1.25-2.56), blood transfusion ≤24 hours postinjury, improvised explosive device blast, first documented shock index ≥0.80, and >4 injury sites were independently associated with CEWI risk. The presence of a non-extremity infection at least 4 days prior to a CEWI diagnosis was associated with lower CEWI risk, suggesting impact of recent exposure to directed antimicrobial therapy. Further assessment of early clinical management will help to elucidate risk factor contribution. The wound classification system provides a comprehensive approach in assessment of injury and clinical factors for the risk and outcomes of an extremity wound infection.

Microbiology of combat-related extremity wounds: Trauma Infectious Disease Outcomes Study.

We present extremity wound microbiology data from 250 combat casualties (2009-2012). Confirmed extremity wound infections (EWIs) were based on clinical and laboratory findings. Suspected EWIs had isolation of organisms from wound cultures with associated signs/symptoms not meeting clinical diagnostic criteria. Colonized wounds had organisms isolated without any infection suspicion. A total of 335 confirmed EWIs (131 monomicrobial and 204 polymicrobial) were assessed. Gram-negative bacteria were predominant (57% and 86% of monomicrobial and polymicrobial infections, respectively). In polymicrobial infections, 61% grew only bacteria, while 30% isolated bacteria and mold. Multidrug resistance was observed in 32% of isolates from first monomicrobial EWIs ±3 days of diagnosis, while it was 44% of isolates from polymicrobial EWIs. Approximately 96% and 52% of the suspected and colonized wounds, respectively, shared ≥1 organism in common with the confirmed EWI on the same patient. Understanding of combat-related EWIs can lead to improvements in combat casualty care.

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.

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

OBJECTIVES: We assessed osteomyelitis risk factors in US military personnel with combat-related open tibia fractures (2003-2009). METHODS: Patients with open tibia fractures who met the diagnostic criteria of osteomyelitis were identified as cases using Military Health System data and verified through medical record review. Controls were patients with open tibia fractures who did not meet osteomyelitis criteria. The Gustilo-Andersen fracture classification scheme was modified to include transtibial amputations (TTAs) as the most severe level. Logistic regression multivariable odds ratios [ORs; 95% confidence intervals (CI)] were assessed. RESULTS: A total of 130 tibia osteomyelitis cases and 85 controls were identified. Excluding patients with TTAs, osteomyelitis cases had significantly longer time to radiographic union compared with controls (median: 210 vs. 165 days). Blast injuries, antibiotic bead utilization, ≥ Gustilo-Andersen-IIIb fractures [highest risk with TTA (OR: 15.10; CI: 3.22-71.07)], and foreign body at the fracture site were significantly associated with developing osteomyelitis. In a separate model, the Orthopaedic Trauma Association Open Fracture Classification muscle variable was significant with increasing risk from muscle loss (OR: 5.62; CI: 2.21-14.25) to dead muscle (OR: 8.46; CI: 3.31-21.64). When TTAs were excluded, significant risk factors were similar and included sustaining an injury between 2003 and 2006. CONCLUSIONS: Patients with severe blast trauma resulting in significant muscle damage are at the highest risk for osteomyelitis. The period association coincides with a time frame when several trauma system practice changes were initiated (eg, increased negative pressure wound therapy, decreased high-pressure irrigation, and reduced crystalloid use). 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.

Immunity After Childhood Vaccinations in Perinatally HIV-exposed Children With and Without HIV Infection in Latin America.

BACKGROUND: Perinatally HIV-infected (PHIV) children are at risk for under-vaccination and poor vaccine response at 4 years of age. Childhood vaccine coverage and immune response were compared between PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean. METHODS: PHIV and HEU children were enrolled prospectively at 15 sites from 2002 to 2009. Full vaccination by age 4 years was defined as: 3 hepatitis B virus vaccine doses; 4 tetanus toxoid-containing vaccine doses; 3 doses of Haemophilus influenzae type b vaccine by age 12 months or ≥1 dose given after age 12 months; one measles-containing vaccine dose; one rubella-containing vaccine dose. Immunity was defined by serum antibody titer. Fisher exact test (for categorical measures) and t test (for continuous measures) were used for comparisons. RESULTS: Among 519 children seen at age 4 years, 191 had serum specimens available (137 PHIV, 54 HEU). Among those with specimens available, 29.3% initiated combination antiretroviral therapy (cART) <12 months of age, 30.9% initiated at ≥12 months of age, and 39.8% had not received cART by the time they were seen at 4 years of age. At 4 years of age, 59.9% were on PI-containing cART (cART/PI), and 20.4% were on no ART. PHIV children were less likely than HEU children to be fully vaccinated for tetanus (55.5% vs. 77.8%, P = 0.005) and measles and rubella (both 70.1% vs. 94.4%, P < 0.001). Among those fully vaccinated, immunity was significantly lower among PHIV than HEU for all vaccines examined: 20.9% versus 37.8% for hepatitis B virus (P = 0.04), 72.0% versus 90.5% for tetanus (P = 0.02), 51.4% versus 68.8% for H. influenzae type b (P = 0.05), 80.2% versus 100% for measles (P < 0.001) and 72.9% versus 98.0% for rubella (P < 0.001) vaccine, respectively. CONCLUSIONS: Compared with HEU, PHIV children were significantly less likely to be immune to vaccine-preventable diseases when fully vaccinated. Strategies to increase immunity against vaccine-preventable diseases among PHIV require further study.

Excess Stress Fractures, Musculoskeletal Injuries, and Health Care Utilization Among Unfit and Overweight Female Army Trainees.

BACKGROUND: Musculoskeletal injuries are prevalent among military trainees and certain occupations. Fitness and body mass index (BMI) have been associated with musculoskeletal conditions, including stress fractures. HYPOTHESIS: The incidence of, and excess health care utilization for, stress fracture and non-stress fracture overuse musculoskeletal injuries during the first 6 months of service is higher among unfit female recruits. Those who exceeded body fat limits are at a greater risk of incident stress fractures, injuries, or health care utilization compared with weight-qualified recruits. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All applicants to the United States Army were required to take a preaccession fitness test during the study period (February 2005-September 2006). The test included a 5-minute step test scored as pass or fail. BMI was recorded at application. There were 2 distinct comparisons made in this study: (1) between weight-qualified physically fit and unfit women and (2) between weight-qualified physically fit women and those who exceeded body fat limits. We compared the incidence of, and excess health care utilization for, musculoskeletal injuries, including stress fractures and physical therapy visits, during the first 183 days of military service. RESULTS: Among the weight-qualified women, unfit participants had a higher non-stress fracture injury incidence and related excess health care utilization rate compared with fit women, with rate ratios of 1.32 (95% CI, 1.14-1.53) and 1.18 (95% CI, 1.10-1.27), respectively. Among fit women, compared with the weight-qualified participants, those exceeding body fat limits had higher rate ratios for non-stress fracture injury incidence and related excess health care utilization of 1.27 (95% CI, 1.07-1.50) and 1.20 (95% CI, 1.11-1.31), respectively. Weight-qualified women who were unfit had a higher incidence of stress fractures and related excess health care utilization compared with fit women, with rate ratios of 1.62 (95% CI, 1.19-2.21) and 1.22 (95% CI, 1.10-1.36), respectively. Among fit women exceeding body fat limits, the stress fracture incidence and related excess health care utilization rate ratios were 0.79 (95% CI, 0.49-1.28) and 1.44 (95% CI, 1.20-1.72), respectively, compared with those who were weight qualified. CONCLUSION: The results indicate a significantly increased risk of musculoskeletal injuries, including stress fractures, among unfit recruits and an increased risk of non-stress fracture musculoskeletal injuries among recruits who exceeded body fat limits. Once injured, female recruits who were weight qualified but unfit and those who were fit but exceeded body fat limits had increased health care utilization. These findings may have implications for military accession and training policies as downsizing of military services will make it more important than ever to optimize the health and performance of individual service members.

Repeat pregnancy in women with HIV infection in Latin America and the Caribbean.

Intended and unintended pregnancies occur frequently among human immunodeficiency virus (HIV)-infected women. We evaluated the occurrence of repeat pregnancy and characteristics associated with this outcome among HIV-infected women in Latin America and the Caribbean who were participating in the National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI). Of the 1342 HIV-infected pregnant women enrolled in NISDI, 124 (9.2%) had one or more repeat pregnancies on study. Median time between the index delivery and date of conception of the subsequent pregnancy was 1.4 years (range 0.1-5.7). Younger age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.04-1.11 per one year decrease in age), hospitalization during the index pregnancy or up to six months post-partum [OR = 2.0, 95% CI: 1.2-3.4], and poor index pregnancy outcome (stillbirth or spontaneous/therapeutic abortion; OR = 3.4, 95% CI: 1.4-8.4) were associated with increased occurrence of repeat pregnancy in multivariable analysis. Among women with repeat pregnancies, the proportion receiving antiretroviral treatment (vs. prophylaxis) increased from 39.4% at the time of the index pregnancy to 81.8% at the time of the repeat pregnancy (p < 0.001). These results can help identify women most likely to benefit from reproductive counseling in order to assist with healthy pregnancy planning and prevention of unintended pregnancies.

Tuberculosis in HIV-infected infants, children, and adolescents in Latin America

Objective: To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. Methods: A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. Results: Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8-64.4%) had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2-26.7%) had clinically confirmed disease and 31.9% (95% CI: 21.2-44.2%) had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. Conclusions: Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized. .

Tuberculosis in HIV-infected infants, children, and adolescents in Latin America.

OBJECTIVE: To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. METHODS: A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. RESULTS: Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8-64.4%) had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2-26.7%) had clinically confirmed disease and 31.9% (95% CI: 21.2-44.2%) had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. CONCLUSIONS: Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized.

Leveraging practice-based research networks to accelerate implementation and diffusion of chronic kidney disease guidelines in primary care practices: a prospective cohort study.

BACKGROUND: Four practice-based research networks (PBRNs) participated in a study to determine whether networks could increase dissemination, implementation, and diffusion of evidence-based treatment guidelines for chronic kidney disease by leveraging early adopter practices. METHODS: Motivated practices from four PBRNs received baseline and periodic performance feedback, academic detailing, and weekly practice facilitation for 6 months during wave I of the study. Each wave I practice then recruited two additional practices (wave II), which received performance feedback and academic detailing and participated in monthly local learning collaboratives led by the wave I clinicians. They received only monthly practice facilitation. The primary outcomes were adherence to primary care-relevant process-of-care recommendations from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Guidelines. Performance was determined retrospectively by medical records abstraction. Practice priority, change capacity, and care process content were measured before and after the interventions. RESULTS: Following the intervention, wave I practices increased the use of ACEIs/ARBs, discontinuation of NSAIDs, testing for anemia, and testing and/or treatment for vitamin D deficiency. Most were able to recruit two additional practices for wave II, and wave II practices also increased their use of ACEIs/ARBs and testing and/or treatment of vitamin D deficiency. CONCLUSIONS: With some assistance, early adopter practices can facilitate the diffusion of evidence-based approaches to other practices. PBRNs are well-positioned to replicate this process for other evidence-based innovations.

Short communication: kidney dysfunction among HIV-infected children in Latin America and the Caribbean.

Renal toxicity is a concern in HIV-infected children receiving antiretrovirals. However, the prevalence [1.7%; 95% confidence interval (CI): 1.0-2.6%] and incidence of kidney dysfunction (0.17 cases/100 person-years; 95% CI: 0.04-0.30) were rare in this multicenter cohort study of 1,032 perinatally HIV-infected Latin American and Caribbean children followed from 2002 to 2011.

Implementing asthma guidelines using practice facilitation and local learning collaboratives: a randomized controlled trial.

PURPOSE: Guideline implementation in primary care has proven difficult. Although external assistance through performance feedback, academic detailing, practice facilitation (PF), and learning collaboratives seems to help, the best combination of interventions has not been determined. METHODS: In a cluster randomized trial, we compared the independent and combined effectiveness of PF and local learning collaboratives (LLCs), combined with performance feedback and academic detailing, with performance feedback and academic detailing alone on implementation of the National Heart, Lung and Blood Institute's Asthma Guidelines. The study was conducted in 3 primary care practice-based research networks. Medical records of patients with asthma seen during pre- and postintervention periods were abstracted to determine adherence to 6 guideline recommendations. McNemar's test and multivariate modeling were used to evaluate the impact of the interventions. RESULTS: Across 43 practices, 1,016 patients met inclusion criteria. Overall, adherence to all 6 recommendations increased (P ≤.002). Examination of improvement by study arm in unadjusted analyses showed that practices in the control arm significantly improved adherence to 2 of 6 recommendations, whereas practices in the PF arm improved in 3, practices in the LLCs improved in 4, and practices in the PF + LLC arm improved in 5 of 6 recommendations. In multivariate modeling, PF practices significantly improved assessment of asthma severity (odds ratio [OR] = 2.5, 95% CI, 1.7-3.8) and assessment of asthma level of control (OR = 2.3, 95% CI, 1.5-3.5) compared with control practices. Practices assigned to LLCs did not improve significantly more than control practices for any recommendation. CONCLUSIONS: Addition of PF to performance feedback and academic detailing was helpful to practices attempting to improve adherence to asthma guidelines.

Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin America and Caribbean countries.

OBJECTIVES: To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women. METHODS: Hypertensive disorders (HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at ≥20 weeks gestation were analyzed. RESULTS: HD were diagnosed in 73 (4.8%, 95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) ≥25 kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) ≥11 g/dL at delivery (OR = 2.1; 95% CI: 1.2-3.6) and age ≥35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was increased among women with a gBMI ≥25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0) and Hg ≥11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9). CONCLUSIONS: HIV-infected women, with a previous history of PE/E, a gBMI ≥25 kg/m(2), Hg at delivery ≥11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy.

Undervaccination of perinatally HIV-infected and HIV-exposed uninfected children in Latin America and the Caribbean.

BACKGROUND: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared. METHODS: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the data. Covariates potentially associated with a child's HIV status were considered in multivariable logistic regression modeling. RESULTS: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models. CONCLUSIONS: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.

Evaluation of viral load thresholds for predicting new World Health Organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy.

BACKGROUND: This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). METHODS: Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. RESULTS: Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. CONCLUSIONS: In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.