A randomized control trial of high-dose micronutrient-antioxidant supplementation in healthy persons with untreated HIV infection.

BACKGROUND: Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). METHODS: This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/µL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/µL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. RESULTS: Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/µL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/µL and -79.763 cells/µL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/µL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. CONCLUSIONS: In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00798772.

Micronutrient deficiency and treatment adherence in a randomized controlled trial of micronutrient supplementation in ART-naïve persons with HIV.

INTRODUCTION: The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection. OBJECTIVE: We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions. METHODS: Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS). RESULTS: Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B12 deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B12 correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B12 per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants. CONCLUSION: Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00798772.

Design and methods of the MAINTAIN study: a randomized controlled clinical trial of micronutrient and antioxidant supplementation in untreated HIV infection.

Micronutrient deficiencies are common in HIV positive persons and are associated with a poorer prognosis, but the role of micronutrient supplementation in the medical management of HIV infection remains controversial, as some but not all studies show immunological and clinical benefit. Micronutrients supplementation could be a relatively low cost strategy to defer the initiation of expensive, potentially toxic and lifelong antiretroviral therapy. The MAINTAIN study is a Canadian multi-center randomized control double blind clinical trial to evaluate if micronutrient supplementation of HIV positive persons slows progression of immune deficiency and delays the need to start antiretroviral therapy and is safe, compared to standard multivitamins. Untreated asymptomatic HIV positive adults will receive a micronutrient and antioxidant preparation (n = 109) or an identical appearing recommended daily allowance multivitamin and mineral preparation (n = 109) for two years. Participants will be followed quarterly and monitored for time from baseline to CD4 T lymphocyte count <350 mm(3), or emergence of CDC-defined AIDS-defining illness, or the start of antiretroviral therapy. We will also compare safety and health related quality of life between groups. Primary analysis will compare the incidence of the composite primary outcome between study groups and will be by intention-to-treat. The study was originally expected to last three years, with accrual over one year and a minimum of two years follow up of the last enrolled participant. We discuss here the study design and methods, often used for evaluation of complementary and adjunctive treatments for health maintenance in HIV infection, which are common interventions.

Pattern of physical injury associated with intimate partner violence in women presenting to the emergency department: a systematic review and meta-analysis.

OBJECTIVE: To examine patterns of physical injury associated with intimate partner violence (IPV) among women presenting to emergency room departments. DATA SOURCES: Systematic searches of Medline, EMBASE, and CINAHL electronic databases from their earliest entries up to February, 2008. Reference lists from the studies included from the electronic database search were reviewed for published and unpublished studies. The authors contacted study authors regarding published and unpublished information. REVIEW METHODS: After titles and abstracts were initially screened by a single reviewer, two reviewers screened the remaining full-text articles for inclusion into the review. Studies were included if they pertained in whole or in part to women who presented to an emergency department because of IPV and reported the location or type of injuries. Studies without comparison groups of non-IPV women and case series/case reports were excluded. The authors performed a meta-analysis of the available data using the random effects model. RESULTS: The authors identified 262 potentially relevant titles and abstracts, of which 7 articles were included in the review. The association between head, neck, or facial injuries and IPV was higher among studies that excluded women with verifiable injuries such as witnessed falls or motor vehicle collisions (pooled odds ratio (OR) 24 (95% CI [15, 38]). Thoracic, abdominal, or pelvic injuries were nonspecific for IPV (pooled OR 1.07 (95% CI [0.89, 1.29]). Injuries in the upper extremities were suggestive of non-IPV etiology (pooled OR 0.51 (95% CI [0.41, 0.54]), as were lower extremity injuries (pooled OR 0.15 (95% CI [0.04, 0.56]). CONCLUSIONS: Among women presenting to emergency room departments, unwitnessed head, neck, or facial injuries are significant markers for IPV. Conversely, extremity injuries are less likely to have been the consequence of IPV.

Single wire versus double wire loops for median sternotomy closure: experimental biomechanical study using a human cadaveric model.

BACKGROUND: Healing of median sternotomy requires reliable sternal fixation. Although both single and double wire kits are commercially available, no experimental study has compared the two closures in a human cadaveric model. We used a recently described human experimental cadaveric model to compare the stability of the closures. METHODS: Sixteen fresh adult human cadaveric sternal plates with adjacent ribs were fixed with custom designed spiked stainless steel clamps and attached to a biomechanical testing device. Single No. 5 peristernal and double peristernal closures were tested. The stability of the unions was tested using perpendicular, repetitive force loads increasing from 0 to 800 Newtons at a rate of 0.5 mm/second. RESULTS: The two study groups did not differ in age or sex. No clamp failures or damage to the specimens occurred. The double peristernal closure exhibited a significantly lower permanent displacement than the single wire group, suggesting a superior strength and stability of that closure. CONCLUSIONS: To the extent to which this human cadaveric model resembles in vivo median sternotomy, these data suggest that the biomechanical stability of the peristernal double wire closure may exceed that of single wires.

Biomechanical comparison of median sternotomy closures.

BACKGROUND: Poor healing of median sternotomy can significantly increase morbidity, mortality, and hospital costs. Effective union requires reliable sternal fixation. Although wire has proven the most reliable and widely used sternotomy closure material, no experimental studies have compared a large variety of wiring techniques in a human model. We developed an easily reproducible experimental model using cadaveric human sterna and compared several wiring methods to assess closure strength and stability. METHODS: Fifty-three fresh adult human cadaveric sternal plates with adjacent ribs were fixed with specially designed spiked stainless steel clamps and attached to a texture analyzer. Single peristernal and transsternal, alternating single peristernal and transsternal, figure-eight peristernal, figure-eight pericostal, and Robicsek closures using no. 5 stainless steel wires were tested. We evaluated bone density, stiffness, and displacement using perpendicular, repetitive variable force loads of 800 Newtons cycling at a rate of 0.5 mm/s. RESULTS: There were no significant differences in age, sex, or bone density in outcome measures of the sternal groups. No clamp failures or clamp damage to the specimens occurred. The single peristernal and alternating peristernal and transsternal closures proved superior in strength and stability (p < 0.001). The figure-eight peristernal, then the single transsternal, then the Robicsek were next stablest groups in decreasing order. The figure-eight pericostal closure had the highest failure rate (p < 0.001). CONCLUSIONS: This novel model of sternotomy closure testing was reliable, inexpensive, and easily reproducible. The mechanical stability of peristernal and alternating peristernal and transsternal wires was significantly greater than that of the other tested methods. Pericostal figure-eight closures were not sufficiently stable to be considered a reliable method of primary sternotomy repair.

Effects of processing conditions on the physical and chemical properties of buckwheat grit cakes.

Buckwheat grit cakes were prepared with a rice cake machine using the following independent variables: tempering moisture contents (15, 17, and 19%, wb), heating temperatures (240, 246, 252, and 258 degrees C), and heating times (5, 6, 7, and 8 s). Higher moisture, higher heating temperature, or longer heating time produced cakes with a higher cake specific volume. Cakes became lighter in color at a lower heating temperature or a shorter heating time. The hardest cake was produced at 252 degrees C for 5 s at 19% moisture content. The percent weight loss after tumbling decreased with increasing heating times and heating temperatures. Increased heating time resulted in more expanded products. The average rutin content decreased as the heating temperature or heating time increased. These results suggest that processing conditions, including tempering moisture, heating temperature, and heating time, significantly influenced physical and chemical qualities of buckwheat grit cakes such as specific volume, hardness, integrity, color, internal structure, and rutin content.

Biomechanical porcine model of median sternotomy closure.

BACKGROUND: Healing complications following median sternotomy commonly include instability, nonunion, and infection. They are associated with a high mortality rate if mediastinitis supervenes. Closure complications are best avoided by improving stability at the union, but there has thus far been no widespread agreement among surgeons about relative superiority among the available closure techniques. MATERIALS AND METHODS: A biological sternotomy closure model was developed utilizing whole porcine sterna. A special stainless-steel clamp with multiple spikes was created to reliably attach the sterna to a biomechanical testing device. RESULTS: Two wiring techniques, single peristernal and pericostal figure-eight, were used in 14 fresh cadaveric porcine sterna. The more rigid closure utilized single peristernal wires (P < 0.0001). There was no tissue associated with clamp spikes penetrating the specimen's layers, and there was no clamp displacement even at closure failure loads. CONCLUSIONS: The porcine sternotomy model is a valuable tool for comparing closure techniques based on geometrical and mechanical wiring patterns. The model's low cost and easy reproducibility make it a promising first step in sternotomy closure research. The stainless-steel clamp used in the porcine model provided reliable repeat specimen fixation.

Evaluation of an Automated Beef Carcass Washing and Sanitizing System under Production Conditions 1, 2.

Beef half carcasses were hand- or machine-washed and then machine-sanitized with 1.5% acetic acid. Sanitizer was applied at 14.4 or 52°C. Counts of Escherichia coli , Enterobacteriaceae and aerobic bacteria, made on samples collected by excision of tissues before and after treatments, demonstrated that machine washing and sanitizing reduced counts more than did hand washing. Counts were reduced more by hot than cool acetic acid. Percentages of samples with counts of log10 5.0/200 cm2 or higher after treatment were 26 and 46 for samples from carcasses sanitized with 1.5% acetic acid at 52 and 14.4°C, respectively. After hand washings 65% of the samples had these high counts.