Study APV20002: Safety and Efficacy Results Through Week 684 for Pediatric Participants Living With HIV-1 Treated With Ritonavir-Boosted Fosamprenavir Oral Solution-Based Antiretroviral Therapy.

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral-experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4+ cell count was 1235 cells/mm3 [n=51] at baseline, 1690 cells/mm3 (n=41) at Week 48, and 1280 cells/mm3 (n=21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.

Neonatal morbidity and mortality in birth centers in the United States 2018-2021: An observational study of low-risk birthing individuals.

BACKGROUND: Many studies reporting neonatal outcomes in birth centers include births with risk factors not acceptable for birth center care using the evidence-based CABC criteria. Accurate comparisons of outcomes by birth setting for low-risk patients are needed. METHODS: Data from the public Natality Detailed File from 2018 to 2021 were used. Logistic regression, including adjusted and unadjusted odds ratios, compared neonatal outcomes (chorioamnionitis, Apgar scores, resuscitation, intensive care, seizures, and death) between centers and hospitals. Covariates included maternal diabetes, body mass index, age, parity, and demographic characteristics. RESULTS: The sample included 8,738,711 births (8,698,432 (99.53%) in hospitals and 40,279 (0.46%) in birth centers). There were no significant differences in neonatal deaths (aOR 1.037; 95% CI [0.515, 2.088]; p-value 0.918) or seizures (aOR 0.666; 95% CI [0.315, 1.411]; p-value 0.289). Measures of morbidity either not significantly different or less likely to occur in birth centers compared to hospitals included chorioamnionitis (aOR 0.032; 95% CI [0.020, 0.052]; p-value < 0.001), Apgar score < 4 (aOR 0.814, 95% CI [0.638, 1.039], p-value 0.099), Apgar score < 7 (aOR 1.075, 95% CI [0.979, 1.180], p-value 0.130), ventilation >6 h (aOR 0.349; [0.281,0.433], p-value < 0.001), and intensive care admission (aOR 0.356; 95% CI [0.328, 0.386], p-value < 0.001). Birth centers had higher odds of assisted neonatal ventilation for <6 h as compared to hospitals (aOR 1.373; 95% CI [1.293, 1.457], p-value < 0.001). CONCLUSION: Neonatal deaths and seizures were not significantly different between freestanding birth centers and hospitals. Chorioamnionitis, Apgar scores < 4, and intensive care admission were less likely to occur in birth centers.

Distress, Social Support, and Self-Compassion: Relationships With Mental Health Among College Students.

This study investigated how distress, conceptualized as an interaction between hassles and stress perceptions, related to mental health, whether the type of distress (social or nonsocial) was consequential, and whether perceived support and self-compassion attenuated these relationships. Students (N = 185) from a mid-sized university in the southeast completed a survey. Survey questions pertained to hassles and stress perceptions, mental health (i.e., anxiety, depression, happiness, and love of life), perceived social support, and self-compassion. As predicted, students reporting more hassles and stress (both social and nonsocial) as well as those reporting less support and self-compassion, were worse off regarding mental illness and mental wellness. This was observed for both social and nonsocial distress. Although we did not support our hypotheses regarding buffering effects, we found perceived support and self-compassion are beneficial, regardless of hassles and stress levels. We discuss implications for students' mental health and ideas for future research.

Humility, Personality, and Psychological Functioning.

As part of the shift to a more positive psychology, researchers have demonstrated a relatively new and intense fascination with humility. Following a discussion of this construct and its correlates, we investigate how humility relates to personality dimensions, anxiety and depression, love of life and happiness, and self-efficacy in two samples-college students and adult Mturk workers. In both studies, we used the Dual Dimension Humility Scale, a measure that does not conflate the construct with honesty. Among students (N = 399), aspects humility correlated with dimensions of personality (more conscientiousness and openness, and less agreeableness and neuroticism), less depression, more love of life and happiness, and stronger social self-efficacy. Although fewer associations were found, overall, among adults (N = 509), aspects of humility correlated with dimensions of personality, less anxiety, and some dimensions of psychological well-being. The most unique contributions of this study include linking humility with college students' love of life and self-efficacy, and with adults' well-being. We conclude with a discussion of ideas for future research and potential applications to boost humility.

Family Unpredictability and Sense of Coherence: Relationships With Anxiety and Depression in Two Samples.

Sense of coherence (SOC) refers to beliefs about how comprehensible, manageable, and meaningful one's life is. We investigated how SOC relates to family of origin unpredictability and psychological functioning in two samples. College students (N=172, 78% female; M=18.9 years old; 78% white/Caucasian) who recalled more family unpredictability while growing up also reported weaker SOC beliefs and poorer mental health. Furthermore, SOC mediated the negative impact of family unpredictability on anxiety but not on depression. Among adults (N=220, 47% female, 50% male, 3% gender nonconforming; M=40.2 years old; 60% Caucasian), correlations among family chaos, SOC, and psychological functioning were even stronger, overall. One mediation was detected: the relationship between family unpredictability and anxiety was partially explained by adults' perceptions regarding the manageability of their life. This is the first study to explore the relationships among SOC, family chaos, and psychological functioning.

Strong Start Innovation: Equitable Outcomes Across Public and Privately Insured Clients Receiving Birth Center Care.

INTRODUCTION: The Birth Center model of care is a health care delivery innovation in its fourth decade of demonstration across the United States. The purpose of this research was to evaluate the model's potential for decreasing poverty-related health disparities among childbearing families. METHODS: Between 2013 and 2017, 26,259 childbearing people received care within the 45 Center for Medicare and Medicaid Innovation Strong Start birth center sites. Secondary analysis of the prospective American Association of Birth Centers Perinatal Data Registry was conducted. Descriptive statistics described sociobehavioral, medical risk factors, and core clinical outcomes to inform the logistic regression model. Privately insured consumers were independently compared with 2 subgroups of Medicaid beneficiaries: Strong Start enrollees (midwifery-led care with peer counselors) and non-Strong Start Medicaid beneficiaries (midwifery-led care without peer counselors). RESULTS: After controlling for medical risk factors, Strong Start Medicaid beneficiaries achieved similar outcomes to privately insured consumers with no significant differences in maternal or newborn outcomes between groups. Perinatal outcomes included induction of labor (adjusted odds ratio [aOR], 0.86; 95% CI 0.61-1.13), epidural analgesia use (aOR, 1.00; 95% CI, 0.68-1.48), cesarean birth (aOR, 1.16; 95% CI, 0.87-1.53), exclusive breastfeeding on discharge (aOR, 1.11; 95% CI, 0.48-2.56), low Apgar score at 5 minutes (aOR, 1.23; 95% CI, 0.86-1.83), low birth weight (aOR, 1.12; 95% CI, 0.77-1.64), and antepartum transfer of care after the first prenatal appointment (aOR, 1.53; 95% CI, 0.97-2.40). Medicaid beneficiaries who were not enrolled in the Strong Start midwifery-led, peer counselor program demonstrated similar results except for having higher epidural analgesia use (aOR, 1.30; 95% CI, 1.10-1.53) and significantly lower exclusive breastfeeding on discharge (aOR, 0.57; 95% CI, 0.40-0.81) than their privately insured counterparts. DISCUSSION: The midwifery-led birth center model of care complemented by peer counselors demonstrated a pathway to achieve health equity.

Salary and Workload of Midwives Across Birth Center Practice Types and State Regulatory Structures.

INTRODUCTION: Expansion of the midwifery-led birth center model of care is one pathway to improving maternal and newborn health. There are a variety of practice types among birth centers and a range of state regulatory structures of midwifery practice across the United States. This study investigated how those variations relate to pay and workload for midwives at birth centers. METHODS: Data from the American Association of Birth Centers Practice Survey and the Bureau of Labor Statistics' report on occupational employment and wage statistics were analyzed to explore how midwife salaries and workload at birth centers compare within and beyond the birth center model. RESULTS: Survey results from 161 birth centers across the United States demonstrate wide variation in nurse-midwife salaries and are inconsistent with nurse-midwife salaries across all settings as reported by the Bureau of Labor Statistics. The reported number of hours worked by midwives within the birth center model is high. Salaries of midwives who work in birth center-only practices were consistently lower than salaries of midwives who worked in blended birth center and hospital practices, independent of the midwife's level of experience, geographic region of the country, and state regulatory structure. DISCUSSION: Further research is needed to understand how to bring salaries and workload for midwives at birth centers into alignment with national averages.

A Case of Brainstem Anesthesia after Retrobulbar Block for Globe Rupture Repair.

PURPOSE: To present a rare case of brainstem anesthesia from retrobulbar block and discuss evidence-based methods for reducing the incidence of this complication. CASE: A 72-year-old female, was given a retrobulbar block of 5 mL of bupivacaine 0.5% for postoperative pain management, after a globe rupture repair under general anesthesia. Prior to injection, the patient was breathing spontaneously via the anesthesia machine circuit and had not received any additional narcotics/muscle relaxants for 2.5 hr (with full recovery of neuromuscular blocking agent after anesthetic reversal). Over 7 min, however, there was a steady increase in ETCO2 and the patient became apneic, consistent with brainstem anesthesia. She remained intubated and was transported to the postanesthesia care unit for prolonged monitoring, with eventual extubation. Discussion. Brainstem anesthesia is an important complication to recognize as it can lead to apnea and death. The judicious use of anesthetic volume, shorter needle tips, and mixed formulations can help reduce the chance of brainstem anesthesia. Observation of the contralateral eye 5-10 minutes after injection for pupillary dilation, and prior to surgical draping, can help identify early CNS involvement.

Improving adult coping with social isolation during COVID-19 in the community through nurse-led patient-centered telehealth teaching and listening interventions.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to social isolation which both threatens mental health and has been shown to increase the risk for early death by 50%, and to contribute to increased rates of heart disease, hypertension, stroke, and inflammation. LOCAL PROBLEM: No identified special programs to address loneliness related to social isolation were in place. This project aimed to improve adult coping with COVID-19 in the community to 80% over 8 weeks. METHODS: Three interventions were implemented concurrently and studied through Plan-Do-Study-Act cycles. Each cycle started with a test of change, followed by data collection and analysis using run charts, aggregate data tables, and field notes. This analysis guided the design of new tests of change for each intervention in the following cycle. Iterative changes were introduced through four cycles over 8th weeks. INTERVENTIONS: These included a data-gathering survey, a telehealth teach-back tool and a telehealth listening tool. All interventions were implemented remotely through telehealth contacts. RESULTS: The project engaged 44 participants and successfully addressed loneliness by creating a social connection with 100% of participants and 82% of participants learned something new. CONCLUSION: Telehealth interventions hardwired to be patient-centered can provide isolated populations with meaningful social contact.

Family factors and depressive symptoms among college students: Understanding the role of self-compassion.

Objective: Poor family support and increased family unpredictability during childhood have been related to subsequent depression. How self-compassion might influence the relation between family factors (ie, unpredictability and support) and depression is unclear. The present study examines how family factors and self-compassion relate to depressive symptoms.Participants: Study participants include 365 university students.Methods: Undergraduate students responded to a questionnaire assessing family factors, recent depressive symptoms, and self-compassion.Results: Hypotheses were supported: family factors were correlated with depression and lower self-compassion, and self-compassion and depression were negatively related. Furthermore, self-compassion moderated the unpredictability-depression relationship. Specifically, individuals who reported high levels of self-compassion demonstrated similar rates of depression, regardless of whether they reported mild, moderate, or high levels of family unpredictability. Self-compassion did not moderate the family support-depression relationship.Conclusions: Implications for therapeutic interventions targeting self-compassion for alleviating depressive symptoms are discussed.

Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30-49 vs ≥50 mL/min.

A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine dosing in patients with impaired creatinine clearance (CLcr). Safety data collected through 96 weeks were analyzed after stratification by baseline CLcr (estimated using Cockcroft-Gault) of 30-49 mL/min (n = 168) versus ≥50 mL/min (n = 3,132) and treatment regimen. The Grade 3-4 adverse events (AEs) and serious AEs (for hematological, hepatic and gastrointestinal events), maximal toxicities for liver enzymes, serum creatinine and bilirubin and maximum treatment-emergent hematology toxicities were comparable for groups with baseline CLcr 30-49 versus CLcr≥50 mL/min. No new risks or trends were identified from this dataset. Substantial and similar increases in the mean creatinine clearance (>25 mL/min) were observed from baseline though Week 96 among participants who entered the trial with CLcr 30-49 mL/min, while no increase or smaller median changes in creatinine clearance (<7 mL/min) were observed for participants who entered the trial with CLcr ≥50 mL/min. Substantial increases (> 150 cells/ mm3) in mean CD4+ cells counts from baseline to Week 96 were also observed for participants who entered the trial with CLcr 30-49 mL/min and those with baseline CLcr ≥50 mL/min. Though these results are descriptive, they suggest that HIV-positive patients with CLcr of 30-49 mL/min would have similar AE risks in comparison to patients with CLcr ≥50 mL/min when initiating antiretroviral therapy delivering doses of 300 mg of lamivudine daily through 96 weeks of treatment. Overall improvements in CLcr were observed for patients with baseline CLcr 30-49 mL/min.

Similar neurocognitive outcomes after 48 weeks in HIV-1-infected participants randomized to continue tenofovir/emtricitabine + atazanavir/ritonavir or simplify to abacavir/lamivudine + atazanavir.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as "impaired" (defined as either a z-score ≤ - 2 or having 2 or more standardized individual test z-scores ≤ - 1); while higher scores (equaling better performance) were classified as "normal". By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p < 0.05) in the baseline-adjusted performance between treatment groups for any individual test or by z-score. Specific demographic and medical risk factors were evaluated by univariate analysis for impact on neurocognitive performance. Factors with p < 0.10 were evaluated by backwards regression analysis to identify neurocognition-correlated factors after accounting for treatment, assessment, and baseline. Four risk factors at baseline for impaired neurocognition were initially identified: lower CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6 levels, and a history of psychiatric disorder not otherwise specified, however none were found to moderate the effect of treatment on neurocognition. In this aviremic, treatment-experienced population, baseline-adjusted neurocognitive function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r-treated and in the ART-simplified ABC/3TC + ATV treatment groups.

Assessment of drug interaction potential between the HCV direct-acting antiviral agents elbasvir/grazoprevir and the HIV integrase inhibitors raltegravir and dolutegravir.

BACKGROUND: Elbasvir/grazoprevir is a once-daily fixed-dose combination therapy for the treatment of chronic HCV infection, including HCV/HIV coinfection. OBJECTIVES: To evaluate the pharmacokinetic interaction of elbasvir and grazoprevir with raltegravir or dolutegravir. METHODS: Three open-label trials in healthy adult participants were conducted. In the raltegravir trials, participants received a single dose of raltegravir 400 mg, a single dose of elbasvir 50 mg or grazoprevir 200 mg, and raltegravir with either elbasvir or grazoprevir. In the dolutegravir trial, participants received a single dose of dolutegravir 50 mg alone or co-administered with once-daily elbasvir 50 mg and grazoprevir 200 mg. RESULTS: The raltegravir AUC0-∞ geometric mean ratio (GMR) (90% CI) was 1.02 (0.81-1.27) with elbasvir and 1.43 (0.89-2.30) with grazoprevir. Dolutegravir AUC0-∞ GMR (90% CI) was 1.16 (1.00-1.34) with elbasvir and grazoprevir. The elbasvir AUC0-∞ GMR (90% CI) was 0.81 (0.57-1.17) with raltegravir and 0.98 (0.93-1.04) with dolutegravir. The grazoprevir AUC0-24 GMR (90% CI) was 0.89 (0.72-1.09) with raltegravir and 0.81 (0.67-0.97) with dolutegravir. CONCLUSIONS: Elbasvir or grazoprevir co-administered with raltegravir or dolutegravir resulted in no clinically meaningful drug-drug interactions and was generally well tolerated. These results support the assertion that no dose adjustments for elbasvir, grazoprevir, raltegravir or dolutegravir are needed for co-administration in HCV/HIV-coinfected people.

Anxiety and Drinking: Are Personal Beliefs Regarding Control and Unpredictability Relevant?

Anxiety and drinking problems are fairly common, and it is important to know what factors affect these issues. Previous studies document that control beliefs are associated with anxiety and drinking. Unpredictability beliefs correlate with anxiety, yet whether they relate to drinking is unknown. The present study explored these relationships in a sample of adults (N = 150; 40.0% female; M = 34.4 years old) and in a sample of college students (N = 182; 74.7% female; M = 18.9 years old). Among adults, unpredictability beliefs correlated with anxiety and control beliefs, but not drinking. Similarly, control beliefs correlated with anxiety but not drinking. Furthermore, anxiety and drinking were uncorrelated. Among undergraduates, unpredictability and control beliefs predicted anxiety, whereas unpredictability (pertaining to the self and others) and internality predicted frequency of drinking. Personal unpredictability beliefs emerged as having the strongest association with anxiety across both samples. Future research and treatment should take into account unpredictability beliefs when addressing anxiety problems.

Changes from 2000 to 2009 in the Prevalence of HIV-1 Containing Drug Resistance-Associated Mutations from Antiretroviral Therapy-Naive, HIV-1-Infected Patients in the United States.

Pre-existing HIV drug resistance can jeopardize first-line antiretroviral therapy (ART) success. Changes in the prevalence of drug resistance-associated mutations (DRMs) were analyzed from HIV-infected, ART-naive, U.S. individuals seeking ART treatment from 2000 to 2009. HIV DRM data from 3,829 ART-naive subjects were analyzed by year of sample collection using International Antiviral Society-United States (IAS-USA) and World Health Organization (WHO) "surveillance" DRM definitions; minor IAS-USA-defined DRMs were excluded. IAS-USA DRM prevalence between 2000 and 2009 was 14%, beginning with 8% in 2000 and 13% in 2009. The greatest incidence was observed in 2007 (17%). Overall, IAS-USA-defined non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were 9.5%; nucleoside reverse transcriptase inhibitor (NRTI): 4%, and major protease inhibitor (PI): 3%. The most frequently detected IAS-USA-defined DRMs by class were NNRTI: K103N/S (4%), NRTI: M41L (1.5%), and PI: L90M (1%). Overall, WHO-defined DRM prevalence was 13% (5% in 2000; 13% in 2009). By class, NNRTI prevalence was 6%, NRTI: 6%, and PI: 3.2%. The most frequent WHO-defined DRMs were NRTI: codon T215 (3.0%), NNRTI: K103N/S (4%), and PI: L90 (1%). WHO-defined NNRTI DRMs declined significantly (p = .0412) from 2007 to 2009. The overall prevalence of HIV-1 containing major IAS-USA or WHO-defined DRMs to ≥2 or ≥3 classes was 2% and <1%, respectively. The prevalence of HIV-1 with WHO-defined dual- or triple-class resistance significantly declined (p = .0461) from 2008 (4%) to 2009 (<1%). In this U.S. cohort, the prevalence of HIV-1 DRMs increased from 2000 onward, peaked between 2005 and 2007, and then declined between 2008 and 2009; the detection of WHO-defined dual- or triple-class DRM similarly decreased from 2008 to 2009.

The genomic road to invasion-examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.

BACKGROUND: It is frequently assumed that pre-invasive lesions are simpler precursors of cancer and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments and early detection methodologies. METHODS: We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. Forty-eight samples from 16 patients were further examined using exome sequencing. RESULTS: Evidence of a shared ancestor of both dysplasia and carcinoma was seen in all but one patient. One-third of dysplasias showed independent copy number events. The remainder had a copy number pattern that was similar to or simpler than that of the carcinoma. All dysplasias examined contained somatic mutations absent in the related carcinoma. Previously observed copy number changes and TP53 mutations were very frequently observed, and almost always shared between dysplasia and carcinoma. Other gene changes were more sporadic. Pathway analysis confirmed that each patient's disease developed in a different way. Examining the numbers of shared mutations and the rate of accumulation of mutations showed evidence that all samples contain a population of sub-clones, with little evidence of selective advantage of a subset of these. CONCLUSIONS: These findings suggest that most of the genomic changes driving oral cancer occur in the pre-cancerous state by way of gradual random accumulation rather than a dramatic single event.

A systematic multidisciplinary initiative for reducing the risk of complications in adult scoliosis surgery.

OBJECTIVE Systematic multidisciplinary approaches to improving quality and safety in complex surgical care have shown promise. Complication rates from complex spine surgery range from 10% to 90% for all surgeries, and the overall mortality rate is 1%-4%. These rates suggest the need for improved perioperative complex spine surgery processes designed to minimize risk and improve quality. METHODS The Group Health Research Institute and Virginia Mason Medical Center implemented a systematic multidisciplinary protocol, the Seattle Spine Team Protocol, in 2010. This protocol involves the following elements: 1) a comprehensive multidisciplinary conference including clinicians from neurosurgery, anesthesia, orthopedics, internal medicine, behavioral health, and nursing, collaboratively deciding on each patient's suitability for surgery; 2) a mandatory patient education course that reviews the risks of surgery, preparation for the surgery, and postoperative care; 3) a dual-attending-surgeon approach involving 1 neurosurgeon and 1 orthopedic spine surgeon; 4) a dedicated specialist complex spine anesthesia team; and 5) rigorous intraoperative monitoring of a patient's blood loss and coagulopathy. The authors identified 71 patients who underwent complex spine surgery involving fusion of 6 or more levels before implementation of the protocol (surgery between 2008 and 2010) and 69 patients who underwent complex spine surgery after the implementation of the protocol (2010 and 2012). All patient demographic variables, including age, sex, body mass index, smoking status, diagnosis of diabetes and/or osteoporosis, previous surgery, and the nature of the spinal deformity, were comprehensively assessed. Also comprehensively assessed were surgical variables, including operative time, number of levels fused, and length of stay. The authors assessed overall complication rates at 30 days and 1 year and detailed deaths, cardiovascular events, infections, instrumentation failures, and CSF leaks. Chi-square and Wilcoxon rank-sum tests were used to assess differences in patient characteristics for patients with a procedure in the preimplementation period from those in the postimplementation period under a Poisson distribution model. RESULTS Patients who underwent surgery after implementation of the Seattle Spine Team Protocol had a statistically significant reduction (relative risk 0.49 [95% CI 0.30-0.78]) in all measured complications, including cardiovascular events, wound infections, other perioperative infections, and implant failures within 30 days after surgery; the analysis was adjusted for age and Charlson comorbidity score. A trend toward fewer deaths in this group was also found. CONCLUSIONS This type of systematic quality improvement strategy can improve quality and patient safety and might be applicable to other complex surgical disciplines. Implementation of these strategies in the treatment of adult spinal deformity will likely lead to better patient outcomes.

HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects.

BACKGROUND: The presence of the HLA-B*57:01 allele in HIV-infected subjects is associated with a higher risk of abacavir-associated hypersensitivity reaction (ABC HSR). HLA-B*57:01 allele prevalence varies in different populations, but HLA-B*57:01 testing with immunological confirmation has had a negative predictive value for ABC HSR between 97 and 100%. METHODS: In the ASSURE study (EPZ113734), the HLA-B*57:01 prevalence in virologically suppressed, antiretroviral treatment-experienced, HIV-infected subjects from the United States, including Puerto Rico, was assessed. RESULTS: Three hundred eighty-five subjects were screened; 13 were HLA-B*57:01 positive and 372 were negative. Only HLA-B*57:01-negative, abacavir-naive subjects were eligible to enroll into the ASSURE trial. Eleven of the 13 subjects who possessed the HLA-B*57:01 allele were white, the other 2 were African-American. There was no geographic clustering of HLA-B*57:01-positive subjects, and the incidence correlated roughly with those states with the greatest numbers of subjects screened. Similarly, there was no statistically significant correlation between subjects who possessed or lacked the allele and age, gender, ethnicity or CD4+ T-cell numbers. The incidence of ABC HSR following abacavir initiation was also evaluated. Only 1 of 199 HLA-B*57:01-negative subjects (an African-American male) randomized to receive abacavir-containing treatment developed symptoms consistent with suspected ABC HSR; ABC HSR was not immunologically confirmed. CONCLUSIONS: These findings confirm the utility of HLA-B*57:01 allele testing to reduce the frequency of ABC HSR. The prevalence of HLA-B*57:01 positivity was higher in white than in African-American subjects. In HLA-B*57:01-negative subjects, suspected ABC HSR is very rare, but should lead to discontinuation of abacavir when ABC HSR cannot be definitively excluded from the differential diagnosis. TRIAL REGISTRATION: The ASSURE (EPZ113734) study was registered on ClinicalTrials.gov registration on April 8th 2010 and the registration number is NCT01102972.

Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks.

PURPOSE: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses. METHODS: A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed. RESULTS: Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males) and most other demographics were similar between groups; more females than males were black (65% vs 25%) and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%). At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r, +344 vs +301 cells/mm3); proportion with treatment-related grade 2-4 adverse events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to 144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and proportions completing the study were similar during the extension phase. Primary withdrawal reasons were loss to follow-up and pregnancy for females and loss to follow-up and other for males. CONCLUSION: Over 144 weeks, no significant gender differences were observed in efficacy, safety, or fasting lipid changes with abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r.