Quantitative Analysis of Stress-Induced Hyperglycemia and Intracranial Blood Volumes for Predicting Mortality After Intracerebral Hemorrhage.

Stress-induced hyperglycemia (SIH) is a neuroendocrine response to acute illness. Although SIH has an adverse association with intracerebral hemorrhage (ICH), quantitative measures and determinants of SIH are not well delineated. In the present study, we objectively evaluated SIH using glycemic gap (GG) and identified its radiological and clinical determinants, with a 5-year retrospective review of charts of ICH patients. We calculated GG using the regression equation (GG = AG -28.7 × HbA1c + 46.7) and evaluated whether GG is an independent predictor of mortality using a multivariate regression model. Radiological volumes of different intracranial compartments were determined using image segmentation software. We correlated GG with different clinical and radiological parameters using Pearson correlation coefficient (PCC), Spearman's rank correlation (SRC), and Wilcoxon rank sum test. Then, we calculated the value of GG associated with mortality. Out of 328 patients, 238 (73%) survived hospitalization and 90 (27%) expired. GG was found to be an independent predictor of mortality (r=0.008, p=0.04). Additionally, GG was positively correlated with intraparenchymal hemorrhage (IPH) volume (PCC=0.185, p<0.01) and intraventricular hemorrhage (IVH) volume (PCC=0.233, p<0.01) and negatively correlated with cerebrospinal fluid (CSF) volume (PCC=-0.151, p<0.01) and brain tissue volume (PCC=-0.099, p=0.08). GG was positively correlated with patients' ICH score (SRC=0.377, p<0.01), Glasgow Coma Scale (GCS) (PCC=-0.356, p<0.01), hydrocephalus (p<0.01), and IVH in the third ventricle (p<0.01). The univariate logistic regression model identified 30.0 mg/dl as the value of GG (AUC=0.655, p<0.01) that predicted mortality with 52.2% sensitivity and 75.2% specificity and defined SIH. In conclusion, GG independently predicts mortality in ICH patients and positively correlates with IPH and IVH volumes. However, causality between the two is not established and would require specifically designed studies.

In-Hospital Morbidity and Mortality of Traumatic Lower-Extremity Amputations.

Traumatic lower-extremity amputations often result in complications and surgical revisions. The authors report the in-hospital morbidity and mortality of traumatic lower-extremity amputations at a metropolitan level I trauma center for a large rural region and compare below-knee (BK) vs higher-level amputation complications. They retrospectively reviewed 168 adult patients during a 10-year period (2005 to 2015) who had a traumatic injury to the lower extremity that required an amputation. Main outcome measurements included amputation level, complication rates, intensive care unit (ICU) admission rates, length of stay, total trips to the operating room (OR), and Injury Severity Score (ISS). A total of 95 patients had through-knee/above-knee (TK/AK) amputations, and 73 patients had BK amputations. The majority of injuries occurred in the non-urban setting. The TK/AK group had higher ICU admission rates (76% vs 35%, P<.0001), longer overall hospital length of stay (22.0 vs 15.5 days, P=.01), more total OR trips (6.5 vs 5.0, P=.04), and higher ISS (17.0 vs 11.5, P<.0001). A complication was experienced by 64% of all patients during the initial hospitalization. The TK/AK group had higher complication rates than the BK group, including wound infection, pulmonary embolus, rhabdomyolysis, compartment syndrome, and death. Patients with TK/AK traumatic amputations have a greater burden of injury with higher complication rates, increased ICU admissions, increased length of stay, and increased ISS and require more return trips to the OR compared with patients with BK amputations. [Orthopedics. 2020;43(6):e561-e566.].

Effect of Tranexamic Acid on Wound Complications and Blood Loss in Total Ankle Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) is a medication that has been shown to decrease blood loss and risk of blood transfusion in total knee and total hip arthroplasty. The purpose of this study was to evaluate the use of TXA in patients undergoing total ankle arthroplasty (TAA). We hypothesized there would be less blood loss and wound complications in patients receiving TXA. METHODS: A retrospective review of 2 patient cohorts operated on by 2 surgeons was performed from 2010 to 2018. We compared a group of TAA patients that did not receive TXA vs a subsequent group that received TXA. Patients received 1g intravenous TXA before the tourniquet was inflated followed by another 1 g after release of the tourniquet. Intraoperative blood loss was recorded and preoperative hemoglobin and hematocrit levels were compared to postoperative levels. Intraoperative and postoperative complications were compared between the 2 groups. A total of 119 patients were included in the study, of whom 55 received TXA. No significant difference existed between the 2 groups in gender, age, body mass index, or Charlson comorbidity index. RESULTS: There was no difference in estimated blood loss, postoperative hemoglobin/hematocrit values or preoperative to postoperative change in hemoglobin/hematocrit values. Additionally, there was no difference in wound complications or overall complication rate between the groups. CONCLUSION: TXA has been shown to be effective in total knee and total hip arthroplasty in decreasing blood loss and transfusion risk. We did not find it to be effective in reducing intraoperative blood loss, perioperative blood loss, or wound complications in TAA. LEVEL OF EVIDENCE: Level III, comparative study.

Prevalence of ligamentous knee injuries in pedestrian versus motor vehicle accidents.

BACKGROUND: The purpose of this study was to determine the prevalence and characteristics of ligamentous knee injuries and to compare patient demographics, associated injuries and hospital stay to pedestrians who did not sustain a ligamentous knee injury. METHODS: A retrospective review of all adult patients presenting as pedestrians struck by a motor vehicle to a level 1 trauma center over a three-year period was performed. Demographics, length of stay, orthopedic and non-orthopedic traumatic injuries were recorded. Magnetic resonance imaging was reviewed for ligamentous, bony and chondral injuries. RESULTS: Five hundred thirty-nine patients were included. Sixty-seven (12.4%) patients sustained a total of 84 ligamentous knee injuries. OF these knee injuries that had MRI (55/84), the majority (96%) were multi-ligamentous in nature. Patients with ligamentous knee injury were more likely to also be affected by traumatic brain injury, solid organ injury, cervical and lumbar spine injury, pelvic ring injuries, distal femur fractures, patella fractures, knee dislocations, tibial plateau fractures, tibial pilon fractures, and deep vein thrombosis when compared to patients who did not sustain ligamentous knee injury. Patients who sustained ligamentous knee injury were more likely to require hospital and intensive care admission and had a longer overall hospital stay. CONCLUSION: Given the high prevalence of ligamentous knee injuries in this patient population, these patients should be thoroughly evaluated for a ligamentous knee injury. If ligamentous knee injury is suspected, MRI should be considered as a majority of these injuries involved multiple structures. Patients with ligamentous knee injuries often had multi-system injuries with resulting longer hospital stay when compared to those without ligamentous knee injuries.

Management of Aneurysmal Subarachnoid Hemorrhage: Variation in Clinical Practice and Unmet Need for Follow-up among Survivors-A Single-Center Perspective.

OBJECTIVE: The purpose of the present study is to investigate the existence and/or prevalence of clinical practice variation in management of aneurysmal subarachnoid hemorrhage (aSAH) and to determine the need for long-term follow-up. METHODS: A single-center study was carried out of patients with aSAH over a 5-year period divided into 2 halves (2.5 years each) before and after addition of a dually trained cerebrovascular neurosurgeon. In-hospital clinical practice, clinical outcome (mortality and discharge destination) and long-term outcome (modified Rankin Scale score and Telephone Interview for Cognitive Status [TICS]) were compared using descriptive summaries and nonparametric tests. RESULTS: Among 251 patients admitted with aSAH, 115 (45.8%) were before the index event, whereas 136 (54.2%) were during the later period. The aneurysm-securing procedure changed from coil embolization to clip ligation (12/115 [10.4%] vs. 84/136 [61.8%]; P < 0.0001) during the latter years. Interventional treatment for cerebral vasospasm has decreased (58/115 [50.4%] vs. 49/136 [36.0%]; P = 0.0002). Patients surviving hospitalization had more clinic follow-up after discharge during the latter period (42/85 [49.4%] vs. 76/105 [72.4%]; P = 0.0012) and ventriculoperitoneal shunt placement for delayed hydrocephalus (1/85 [1.2%] vs. 9/105 [8.6%]; P = 0.02). A subcohort of aSAH survivors (n = 46) had lower median TICS score during the earlier study period (31.5 [interquartile range, 22-36] vs. 33 [interquartile range, 27-38]; P = 0.038). Similarly, preictal smoking status and hyperlipidemia were associated with adverse TICS score in a multivariate model (P = 0.007). CONCLUSIONS: Postdischarge clinical follow-up has improved facilitating recognition and treatment of delayed hydrocephalus. Existence of cognitive deficits among survivors calls for establishment of multidisciplinary clinics for long-term management of aSAH.

Complication Rates in Total Knee Arthroplasty Performed for Osteoarthritis and Post-Traumatic Arthritis: A Comparison Study.

BACKGROUND: The number of total knee arthroplasty (TKA) procedures performed in the United States has been increasing. Increased complication rates have been demonstrated in patients with post-traumatic arthritis (PTA) undergoing TKA. However, there remains limited data directly comparing outcomes of TKA performed for osteoarthritis (OA) and PTA. METHODS: The National Inpatient Sample was utilized to identify patients undergoing elective TKA between 2006 and 2015 for OA and PTA. The prevalence of preoperative comorbidities and the incidence of postoperative complications including superficial wound infection, deep joint infection, acute deep venous thrombosis, and pulmonary embolus were analyzed. RESULTS: Between 2006 and 2015, the National Inpatient Sample database accounted for 1,301,394 patients diagnosed with either PTA (14,206) or OA (1,287,188) undergoing TKA. The incidence of superficial wound infection, deep joint infection, and acute deep venous thrombosis was found to occur at a higher rate in patients with a diagnosis of PTA compared to OA. The incidence of pulmonary embolus was not found to be statistically different between the 2 groups. Patients with PTA had a higher prevalence of drug and alcohol abuse, psychosis, and liver disease, whereas patients with OA had a higher prevalence of obesity, diabetes, heart disease, and lung disease. CONCLUSION: This study demonstrates an increased risk of complications in patients undergoing TKA for PTA compared to OA. Surgeons can use this information to help aid in counseling patients preoperatively. Furthermore, these data provide objective evidence that could have implications with regards to establishing bundled payment reimbursement in this patient population.

Systemic response of coated-platelet and peripheral blood inflammatory cell indices after aneurysmal subarachnoid hemorrhage and long-term clinical outcome.

PURPOSE: Post-hemorrhage period after aneurysmal subarachnoid hemorrhage (aSAH) has several systemic manifestations including prothrombotic and pro-inflammatory states. Inter-relationship between these states using established/routine laboratory biomarkers and its long-term effect on clinical outcome is not well-defined. MATERIALS AND METHODS: Retrospective analysis of prospective cohort of 44 aSAH patients. Trend of procoagulant biomarkers [coated-platelets, mean platelet volume to platelet count (MPV:PLT)] and peripheral inflammatory biomarkers [platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NLR)] were analyzed using regression analysis. Occurrence of delayed cerebral ischemia (DCI), modified Rankin score (mRS) of 3-6 and Montreal cognitive assessment (MoCA) of <26 at 1-year defined adverse clinical outcome. RESULTS: Patients with worse mRS and MoCA score had higher rise in coated-platelet compared to those with better scores [20.4 (IQR: 15.6, 32.9) vs. 10.95 (IQR: 6.1, 18.9), p = 0.003] and [16.9 (IQR: 13.4, 28.1) vs. 10.95 (IQR: 6.35, 18.65), p = 0.02] respectively. NLR and PLR trends showed significant initial decline followed by a gradual rise in NLR among those without DCI as compared to persistent low levels in those developing DCI (0.13 units/day vs. -0.07 units/day, p = 0.06). CONCLUSIONS: Coated-platelet rise after aSAH is associated with adverse long-term clinical outcome. NLR and PLR trends show an early immune-depressed state after aSAH.

Surgical Gowning Technique: Are We Contaminated Before We Cut?

OBJECTIVES: To assess possible breaches of sterility during the initial gowning step. DESIGN: Observational study. Twenty-seven gowning events were monitored for contamination during a simulated two-person gowning process in which a surgical technician assists a surgeon in the gowning process at the beginning of a surgical procedure. The lower portion of the technician's gown was coated with resin powder before the gowning process to simulate contamination. SETTING: Single-institution Level 1 trauma center. PARTICIPANTS: Three physicians and 3 tenured surgical technicians. INTERVENTION: Observed contaminated areas represented by ultraviolet resin powder under ultraviolet light on the gown of the surgeon after the two-person gowning step. MAIN OUTCOME MEASUREMENT: Number and surface area of contamination events. RESULTS: There was a 66.67% rate of contamination of the surgeon's gown sleeves while being gowned by a surgical technician. The overall median contamination for the short surgeon was 1.3 cm. For the medium height surgeon, the overall median contamination was 1.4 cm. The tall surgeon had an overall median contamination of 2.9 cm. Of the short, medium, and tall surgeons, the number of contamination events was 6, 5, and 7, respectively. The study suggested that the surgeon's height was a significant source of variation (P = 0.046). CONCLUSION: We present an observational pilot study that suggests that to reduce contamination in the operating room, the two-person method must be highly monitored. This study also proposes that the single-person gowning technique should be used to reduce contamination rate during the gowning process.

Radiological Estimation of Intracranial Blood Volume and Occurrence of Hydrocephalus Determines Stress-Induced Hyperglycemia After Aneurysmal Subarachnoid Hemorrhage.

Acute phase after aneurysmal subarachnoid hemorrhage (aSAH) is associated with several metabolic derangements including stress-induced hyperglycemia (SIH). The present study is designed to identify objective radiological determinants for SIH to better understand its contributory role in clinical outcomes after aSAH. A computer-aided detection tool was used to segment admission computed tomography (CT) images of aSAH patients to estimate intracranial blood and cerebrospinal fluid volumes. Modified Graeb score (mGS) was used as a semi-quantitative measure to estimate degree of hydrocephalus. The relationship between glycemic gap (GG) determined SIH, mGS, and estimated intracranial blood and cerebrospinal fluid volumes were evaluated using linear regression. Ninety-four [94/187 (50.3%)] among the study cohort had SIH (defined as GG > 26.7 mg/dl). Patients with SIH had 14.3 ml/1000 ml more intracranial blood volume as compared to those without SIH [39.6 ml (95% confidence interval, CI, 33.6 to 45.5) vs. 25.3 ml (95% CI 20.6 to 29.9), p = 0.0002]. Linear regression analysis of mGS with GG showed each unit increase in mGS resulted in 1.2 mg/dl increase in GG [p = 0.002]. Patients with SIH had higher mGS [median 4.0, interquartile range, IQR 2.0-7.0] as compared to those without SIH [median 2.0, IQR 0.0-6.0], p = 0.002. Patients with third ventricular blood on admission CT scan were more likely to develop SIH [67/118 (56.8%) vs. 27/69 (39.1%), p = 0.023]. Hence, the present study, using unbiased SIH definition and objective CT scan parameters, reports "dose-dependent" radiological features resulting in SIH. Such findings allude to a brain injury-stress response-neuroendocrine axis in etiopathogenesis of SIH.

Sofosbuvir Plus Ribavirin Without Interferon for Treatment of Acute Hepatitis C Virus Infection in HIV-1-Infected Individuals: SWIFT-C.

Background: Historically, acute hepatitis C virus (HCV) infection was treated with shorter durations of interferon-containing therapies. In the era of direct-acting antivirals (DAAs), it is unclear whether the efficacy of treatment achieved in chronic infection can be maintained with abbreviated courses of therapy during the acute phase. Methods: The sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals (SWIFT-C) is an open-label, 2-cohort clinical trial in which the first cohort assessed for the safety and efficacy of 12 weeks of sofosbuvir plus ribavirin for the treatment of acute HCV infection in participants with chronic human immunodeficiency virus type 1 (HIV-1) infection. This is a preplanned analysis of the first cohort, which had a planned accrual of 17 participants. Results: Seventeen men (11 Hispanic, 6 white, median age 45 years) were enrolled. Most (88%) had HCV genotype-1 infection and few (24%) had the favorable IL28B CC genotype. Median baseline HCV RNA was 2 280 000 IU/mL (interquartile range, 272 000-4 230 000). Ten participants (59%) achieved the primary outcome of SVR12 (90% confidence interval, 36%-78%), failing to establish noninferiority. All treatment failures were due to viral relapse (41%). There were no premature treatment discontinuations. The only factor that differed between participants who achieved SVR vs those who relapsed was ribavirin concentration at the end of treatment. Conclusion: Sofosbuvir-ribavirin for 12 weeks for the treatment of acute HCV genotype-1 infection in HIV-1-infected persons results in a high relapse rate. Preliminary studies of DAA combination therapies suggest improved response rates, although the adequate duration of therapy remains unclear. Clinical Trials Registration: NCT02128217.

Effects of Pegylated Interferon/Ribavirin on Bone Turnover Markers in HIV/Hepatitis C Virus-Coinfected Patients.

HIV/hepatitis C virus (HCV) patients have a 3-fold increased fracture incidence compared to uninfected patients. The impact of HCV therapy on bone health is unclear. We evaluated bone turnover markers (BTM) in well-controlled (HIV RNA <50 copies/ml) HIV/HCV-coinfected patients who received pegylated interferon-α and ribavirin (PEG-IFN/RBV) in ACTG trial A5178. Early virologic responders (EVR: ≥2 log HCV RNA drop at week 12) continued PEG-IFN/RBV and non-EVRs were randomized to continuation of PEG-IFN alone or observation. We assessed changes in C-terminal telopeptide of type 1 collagen (CTX; bone resorption marker) and procollagen type I intact N-terminal propeptide (P1NP; bone formation marker), and whether BTM changes were associated with EVR, complete early virologic response (cEVR: HCV RNA <600 IU/ml at week 12), or PEG-IFN treatment. A total of 192 subjects were included. After 12 weeks of PEG-IFN/RBV, CTX and P1NP decreased: -120 pg/ml and -8.48 µg/liter, respectively (both p < 0.0001). CTX declines were greater in cEVR (N = 91; vs. non-cEVR (N = 101; p = 0.003). From week 12 to 24, CTX declines were sustained among EVR patients who continued PEG-IFN/RBV (p = 0.027 vs. non-EVR) and among non-EVR patients who continued PEG-IFN alone (p = 0.022 vs. Observation). Median decreases of P1NP in EVR vs. non-EVR were similar at weeks 12 and 24. PEG-IFN-based therapy for chronic HCV markedly reduces bone turnover. It is unclear whether this is a direct IFN effect or a result of HCV viral clearance, or whether they will result in improved bone mineral density. Further studies with IFN-free regimens should explore these questions.

Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks.

OBJECTIVES: To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV-HBV co-infected patients receiving HBV-active antiretrovirals. METHODS: One hundred and fifteen HIV-HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound. RESULTS: The proportion with HBV DNA below 200 IU/ml was 60% (95% confidence interval 50-69%) at 24 weeks and 79% (95% confidence interval 69-88%) at 144 weeks. Pretreatment factors associated with the primary outcome were HBV DNA, CD4 T-cell count, and aspartate aminotransferase, but only pretreatment HBV DNA remained associated with long-term suppression (P < 0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual-therapy group achieved HBV DNA below 200 IU/ml (P = 0.007). A higher proportion of hepatitis B e antigen-negative patients (n = 57) achieved HBV DNA below 200 IU/ml at any point, regardless of the therapy group. All 12 patients with emergence of lamivudine-resistant mutants were in the monotherapy group. CONCLUSIONS: TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV-HBV co-infected patients. In resource-limited settings in which TDF may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication.

A randomized, single-blinded, prospective study that compares complications between cuffed and uncuffed nasal endotracheal tubes of different sizes and brands in pediatric patients.

STUDY OBJECTIVE: To compare any association between the problematic distal placement of cuffed and uncuffed nasal endotracheal tubes (NETTs) of different sizes and brands in pediatric patients. DESIGN: Randomized, single-blinded, prospective study. SETTING: Operating room at The Children's Hospital. PATIENTS: Pediatric patients (aged 2-18 years) scheduled for dental surgery under general anesthesia whose American Society of Anesthesiologists physical status is not greater than 2. INTERVENTION: Patients were randomly assigned to preformed cuffed (1) RAE (Ring-Adair-Elwyn) endotracheal tube by Mallinckrodt or (2) nasal AGT NETT by Rüsch. MEASUREMENTS: The distance between the tube's distal end and the carina was measured using a fiber optic bronchoscope. Problematic placements were defined where the tip of the tubes was within 0.5 cm of carina. MAIN RESULTS: The odds of a problematic placement was 7 times higher (95% confidence interval of odds ratio, 2.06, 23.4) in patients managed with cuffed tubes than those with uncuffed tubes (P = .002). The distance between the tip of cuffed NETT tubes and carina was significantly less than with uncuffed tubes. CONCLUSIONS: The chances of possible complications were significantly higher with cuffed NETT. The NETT should be kept at least 0.5 cm above carina to avoid possible complications.

Virologic and serologic outcomes of mono versus dual HBV therapy and characterization of HIV/HBV coinfection in a US cohort.

OBJECTIVES: To characterize HIV/hepatitis B virus (HBV) coinfection in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort and compare long-term HBV outcomes between regimens with 1 (MONO) or 2 (DUAL) anti-HBV agents. DESIGN: A retrospective study of coinfected AIDS Clinical Trials Group Longitudinal Linked Randomized Trials subjects who received regimens containing anti-HBV agent(s). METHODS: Stored samples at baseline and weeks 16, 32, 48, 144, and 240 were tested for HBV DNA, HBV e antigen (HBeAg), HBV e antibody (HBeAb), and hepatitis D virus (HDV) antibody. Resistance and genotype were tested in samples with HBV DNA >600 IU/mL. MONO versus DUAL analyses were limited to HBV treatment-naive subjects (Naive-MONO, Naive-DUAL). RESULTS: Of 150 study subjects, median age was 40 years, 96% were male; 57% white, 26% black, 13% Hispanic. Baseline median CD4 was 224 cells per cubic millimeter, HIV RNA 4.48 log10 copies/mL, HBV DNA 6.30 log10 IU/mL; 59% HBeAg positive and 65% HBeAb negative; HBV genotypes A = 69%, G = 18%, D = 7%, <2% for A/G, B, C, F, H. Coinfection with HDV was 2%. There were 49 Naive-MONO (lamivudine) and 22 Naive-DUAL (11 lamivudine + tenofovir, 11 emtricitabine + tenofovir) with detectable HBV DNA. In the 240-week follow-up, HBV DNA suppression was not significantly higher in Naive-DUAL (P = 0.14); lower baseline HBV DNA (P < 0.01) was associated with suppression. Among 32 Naive-MONO subjects with detectable HBV DNA at baseline and results at week 48, 41% suppressed; among such 15 Naive-DUAL subjects, 53% suppressed. HBeAg and HBeAb analyses showed similar trends. CONCLUSIONS: While consistent trends toward increased HBV DNA suppression, HBeAg loss and HBeAb seroconversion were observed in Naive-DUAL compared with Naive-MONO, they were not statistically significant. Overall, HDV coinfection was low.

V.O2 Kinetics and clinical factors among patients with peripheral artery disease.

PURPOSE: To investigate the association between oxygen uptake (V.O2) kinetics and demographic, behavioral, and clinical factors among patients with peripheral artery disease (PAD). METHODS: A total of 85 PAD patients with intermittent claudication performed a constant load treadmill test, and breath-by-breath (V.e.)O2 was obtained to assess V.O2 kinetics. Demographic information, anthropometry, cardiovascular risk factors, and comorbid conditions were recorded. RESULTS: Using univariate analyses, higher values of tau ([τ], i.e., slowed V.O2 kinetics) were associated with female gender, non-Caucasian race, hypertension, dyslipidemia, and age ≤66 years. Smoking, diabetes, obesity, metabolic syndrome, height, and ankle brachial index were not significantly related to V.O2 kinetics. Using multiple regression procedures, the identified predictors of slowed V.O2 kinetics were female gender (4.76 [95% CI: 1.49-8.03] seconds; P = .0049), non-Caucasian race (4.70 [95% CI: 1.29-8.12] seconds; P = .0075), hypertension (12.06 [95% CI: 8.83-15.28] seconds; P < .0001), and age ≤66 years (4.97 [95% CI: 1.95-7.99] seconds; P = .0015). CONCLUSIONS: In PAD patients, slowed V.O2 kinetics are associated with demographic and clinical factors. The clinical significance is that female, non-Caucasian, and hypertensive PAD patients present central and/or peripheral limitations that may partially account for their walking impairment.

Hepatitis C virus/HIV coinfection and responses to initial antiretroviral treatment.

OBJECTIVE: To explore the relationship between hepatitis C virus (HCV)/HIV coinfection and responses to initial antiretroviral treatment (ART). METHODS: Four AIDS Clinical Trials Group HIV treatment studies' data were combined to compare initial ART responses between HCV/HIV-coinfected and HIV-monoinfected patients as evaluated by virologic failure, CD4 cell measures, occurrence of AIDS/death and grade 3/4 safety events, using Kaplan-Meier estimates and proportional hazard, regression and mixed effects models, adjusting for baseline covariates. RESULTS: Of the 3041 included participants, 81% were men, 19% had prior history of AIDS, the median (25th, 75th percentile) baseline HIV RNA was 4.72 (4.38-5.18) log10 copies/ml, and the median (25th, 75th percentile) baseline CD4 cell count was 216.0 (76.5-327.0) cells/µl. The 279 HCV/HIV-coinfected individuals were older (44 vs. 37 years), more likely to be black non-Hispanic (47 vs. 36%), and previous/current intravenous drug user (52 vs. 5%) than the 2762 HIV-monoinfected patients (all P values <0.001). HCV/HIV coinfection was associated with earlier virologic failure, hazard ratio (95% confidence interval): 1.43 (1.07-1.91); smaller mean CD4 cell increase and CD4% increase [-33.8 (-52.2 to -15.4) cells/µl and -1.16% (-1.43 to -0.89%), respectively] over a median of 132 weeks of follow-up; earlier occurrence of grade 3/4 safety event, hazard ratio 1.51 (1.26-1.81); and increased AIDS/mortality, hazard ratio 2.10 (1.31-3.37). Treatment effects comparing antiretroviral regimens were not significantly different by HCV/HIV coinfection status. CONCLUSION: HCV/HIV coinfection is associated with attenuated response to ART. Results support earlier initiation of HIV therapy and increased monitoring of those initiating ART with HCV/HIV coinfection.

In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use.

BACKGROUND: Among patients with hepatitis C virus (HCV) monoinfection, 25-hydroxyvitamin D [25(OH)D] concentrations are positively associated with a response to peg-interferon/ribavirin. Data on the relation between 25(OH)D concentrations and HCV treatment response in HIV-infected patients are limited. OBJECTIVE: The objective was to determine whether baseline 25(OH)D concentrations predict virologic response in HIV/HCV co-infected patients and to examine variables associated with 25(OH)D concentrations ≥30 ng/mL. DESIGN: Data and samples from 144 HCV genotype 1, treatment-naive patients from a completed HCV treatment trial were examined in this retrospective study. Early virologic response (EVR) was defined as ≥2 log10 reduction in HCV RNA and/or HCV RNA <600 IU/mL at week 12 of peg-interferon/ribavirin treatment. Baseline 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. RESULTS: Compared with the non-EVR control group (n = 68), the EVR group (n = 76) was younger, had fewer cirrhotic subjects, had a higher proportion with the IL28B CC genotype, had a higher albumin concentration, and had a lower HCV viral load at baseline (P ≤ 0.05). The difference in baseline 25(OH)D concentrations between EVR and non-EVR patients was not statistically significant (median: 25 ng/mL compared with 20 ng/mL; P = 0.23). Similar results were found for sustained virologic response (SVR). In multivariable analysis, white and Hispanic race-ethnicity (OR: 6.26; 95% CI: 2.47, 15.88; P = 0.0001) and ritonavir use (OR: 2.68; 95% CI: 1.08, 6.65; P = 0.033) were associated with higher 25(OH)D concentrations (≥30 ng/mL). CONCLUSION: Baseline 25(OH)D concentrations did not predict EVR or SVR. Because ritonavir impairs the conversion of 25(OH)D to the active metabolite, utilization of 25(OH)D may have been impaired in subjects taking ritonavir. This trial was registered at www.clinicaltrials.gov as NCT00078403.

Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort.

OBJECTIVE: To understand the HIV-hepatitis B virus (HBV) epidemic from a global perspective by clinically and virologically characterizing these viruses at the time of antiretroviral therapy (ART) initiation in a multinational cohort. METHODS AND DESIGN: HIV-infected patients enrolled in two international studies were classified as HIV-HBV coinfected or HIV monoinfected prior to ART. HIV-HBV coinfected patients were tested for HBV characteristics, hepatitis D virus (HDV), a novel noninvasive marker of liver disease, and drug-resistant HBV. Comparisons between discrete covariates used χ or Fisher's exact tests (and Jonchkheere-Terpstra for trend tests), whereas continuous covariates were compared using Wilcoxon Rank-Sum Test. RESULTS: Of the 2105 HIV-infected patients from 11 countries, the median age was 34 years and 63% were black. The 115 HIV-HBV coinfected patients had significantly higher alanine aminotransferase and aspartate aminotransferase values, lower BMI, and lower CD4 T-cell counts than HIV monoinfected patients (median 159 and 137 cells/µl, respectively, P = 0.04). In the coinfected patients, 49.6% had HBeAg-negative HBV, 60.2% had genotype A HBV, and 13% were HDV positive. Of the HBeAg-negative patients, 66% had HBV DNA 2000 IU/ml or less compared to 5.2% of the HBeAg-positive individuals. Drug-resistant HBV was not detected. CONCLUSION: Screening for HBV in HIV-infected patients in resource-limited settings is important because it is associated with lower CD4 T-cell counts. In settings in which HBV DNA is not available, HBeAg may be useful to assess the need for HBV treatment. Screening for drug-resistant HBV is not needed prior to starting ART in settings in which this study was conducted.

Identification by primary care clinicians of patients with obstructive sleep apnea: a practice-based research network (PBRN) study.

BACKGROUND: Obstructive sleep apnea (OSA) is a reasonably common disorder that is associated with daytime tiredness and a host of medical conditions. Little is known about how primary care clinicians (PCCs) detect, diagnose, and manage patients who have OSA. METHODS: We gathered information from 44 randomly selected practices in 5 regional practice-based research networks. This included interviews with PCCs and sleep consultants, medical records abstraction, and patient surveys. Descriptive analyses of the quantitative data were used to describe the prevalence of sleep symptoms, the proportion of primary care patients at high risk for OSA, and the methods used by PCCs to detect and diagnose patients with OSA. RESULTS: More than 90% of adult patients visiting a PCC on any given day are experiencing sleep-related symptoms. Based on their Berlin Questionnaire scores, more than one third are at high risk of having sleep apnea. However, most patients have not discussed their sleep-related symptoms with their PCC, and fewer than one third have sleep-related symptoms documented in their medical records. Very few PCCs routinely screen for OSA, and, despite using billing records, problem lists, clinician and staff recall, and prospective logs enhanced by waiting room posters, PCCs were generally unable to identify 25 patients with OSA in their practices. CONCLUSIONS: A substantial proportion of patients who see PCCs regularly are at high risk for OSA. Very few of them are being diagnosed or treated. Clearer guidelines and a systematic approach are needed if this is indeed a problem that should be addressed.