With decreasing mortality in PICUs, a growing number of survivors experience long-lasting physical impairments. Early physical rehabilitation and mobilization during critical illness are safe and ...feasible, but little is known about the prevalence in PICUs. We aimed to evaluate the prevalence of rehabilitation for critically ill children and associated barriers.
National 2-day point prevalence study.
Eighty-two PICUs in 65 hospitals across the United States.
All patients admitted to a participating PICU for greater than or equal to 72 hours on each point prevalence day.
None.
The primary outcome was prevalence of physical therapy- or occupational therapy-provided mobility on the study days. PICUs also prospectively collected timing of initial rehabilitation team consultation, clinical and patient mobility data, potential mobility-associated safety events, and barriers to mobility. The point prevalence of physical therapy- or occupational therapy-provided mobility during 1,769 patient-days was 35% and associated with older age (adjusted odds ratio for 13-17 vs < 3 yr, 2.1; 95% CI, 1.5-3.1) and male gender (adjusted odds ratio for females, 0.76; 95% CI, 0.61-0.95). Patients with higher baseline function (Pediatric Cerebral Performance Category, ≤ 2 vs > 2) less often had rehabilitation consultation within the first 72 hours (27% vs 38%; p < 0.001). Patients were completely immobile on 19% of patient-days. A potential safety event occurred in only 4% of 4,700 mobility sessions, most commonly a transient change in vital signs. Out-of-bed mobility was negatively associated with the presence of an endotracheal tube (adjusted odds ratio, 0.13; 95% CI, 0.1-0.2) and urinary catheter (adjusted odds ratio, 0.28; 95% CI, 0.1-0.6). Positive associations included family presence in children less than 3 years old (adjusted odds ratio, 4.55; 95% CI, 3.1-6.6).
Younger children, females, and patients with higher baseline function less commonly receive rehabilitation in U.S. PICUs, and early rehabilitation consultation is infrequent. These findings highlight the need for systematic design of rehabilitation interventions for all critically ill children at risk of functional impairments.
HIV-1 controllers are patients who control HIV-1 viral replication without antiretroviral therapy. Control is achieved very early in the course of infection, but the mechanisms through which viral ...replication is restricted are not fully understood. We describe a patient who presented with acute HIV-1 infection and was found to have an HIV-1 RNA level of <100copies/mL. She did not have any known protective HLA alleles, but significant immune activation of CD8+ T cells and natural killer (NK) cells was present, and both cell types inhibited viral replication. Virus cultured from this patient replicated as well in vitro as virus isolated from her partner, a patient with AIDS who was the source of transmission. Virologic breakthrough occurred 9months after her initial presentation and was associated with an increase in CD4+ T cell activation levels and a significant decrease in NK cell inhibitory capacity. Remarkably, CD8+ T cell inhibitory capacity was preserved and there were no new escape mutations in targeted Gag epitopes. These findings suggest that fully replication-competent virus can be controlled in acute HIV-1 infection in some patients without protective HLA alleles and that NK cell responses may contribute to this early control of viral replication.
•We show that an HIV-1 controller was infected with pathogenic virus yet maintained low viral loads during primary infection.•She had activated NK cells and CD8+ T cells and both cell types suppressed HIV-1 replication shortly after infection.•She eventually lost control of viral replication, and this was associated with a reduction in NK cell suppressive activity.
HIV-1 controllers are patients who control the virus without HIV-1 medications. These patients may teach us how to design a vaccine against HIV-1. Little is known about how the virus is controlled in the early phase of infection in these patients. Here we show that a recently infected HIV-1 controller had a strong natural killer cell response to the virus. Interestingly, she lost control of the virus 9months later and her natural killer cell response to the virus was diminished. Our work suggests that natural killer cells may have contributed to viral control in the early phase of infection.
Diamond has recently successfully commissioned a major change in the lattice consisting of the substitution of a standard double-bend achromat (DBA) cell with a modified four-bend achromat (4BA) cell ...called “double-double bend achromat” (DDBA). This work stems from the original studies initiated in 2012 towards a Diamond upgrade and provides the benefit of an additional straight section in the ring available for insertion devices. This paper reviews the DDBA design and layout, the implications for technical subsystems, the associated engineering challenges and the main results of the commissioning completed in April 2017.
Background: Casein phosphopeptide‐amorphous calcium phosphate (CPP‐ACP) is an anticariogenic agent that is suitable to be added to foods. The aim of this double‐blind, three‐way crossover randomized ...study was to investigate the capacity of CPP‐ACP, when added to bovine milk, to remineralize enamel subsurface lesions in situ.
Methods: Ten subjects drank 100 mL of bovine milk containing no added CPP‐ACP (control milk), 0.2% (w/v) CPP‐ACP or 0.3% (w/v) CPP‐ACP, for 30 seconds once daily for 15 days, whilst wearing removable appliances with attached slabs of enamel containing subsurface enamel lesions. After each treatment and a one‐week washout period, subjects crossed over to another treatment and this was repeated until they had consumed each of the three milk products. At the completion of each treatment the enamel slabs were removed and remineralization was determined using microradiography.
Results: The results demonstrated that all three milk samples remineralized enamel subsurface lesions in situ. However, the two milk samples containing added CPP‐ACP each produced significantly greater remineralization than the control milk.
Conclusions: The remineralizing effect of CPP‐ACP in milk was dose‐dependent with milk containing 0.2% CPP‐ACP and 0.3% CPP‐ACP producing an increase in mineral content of 81% and 164%, respectively, relative to the control milk.
Abstract Objective. Coping strategies are a predictor of abstinence among patients with substance use disorders. However, little is known regarding the role of coping strategies in the effectiveness ...of the Community Reinforcement Approach (CRA). Using data from a 12 week randomized control trial assessing the effectiveness of the Therapeutic Education System (TES), a web-delivered version of the CRA combined with contingency management, we tested the role of coping strategies as a mediator of treatment effectiveness. Methods 507 participants entering 10 outpatient addiction treatment programs received either treatment-as-usual (TAU), a counselor-delivered treatment (Arm 1), or reduced TAU plus TES wherein 2 h of TAU per week were replaced by TES (Arm 2). Abstinence from drugs and alcohol was evaluated using urine toxicology and self-report. Coping strategies were measured using the Coping Strategies Scale-Brief Version. Mediation analyses were done following Baron and Kenny's and path analysis approaches. Results The average baseline coping strategies scores were not significantly different between the two treatment arms. Overall, TES intervention was significantly associated with higher coping strategies scores when accounting for baseline scores ( F1,1342 = 8.3, p = 0.004). Additionally, higher coping strategies scores at week 12 were associated with an increased likelihood of abstinence during the last 4 weeks of the treatment, while accounting for treatment assignment and baseline abstinence. The effect of TES intervention on abstinence was no longer significant after controlling for coping strategies scores at week 12. Conclusion Our results support the importance of coping skills as a partial mediator of the effectiveness of a web-version of the CRA combined with contingency management.
Longitudinal analyses investigated (a) the co-occurrence of marijuana use and conventional cigarette smoking within time and (b) bidirectional associations between marijuana and conventional ...cigarette use in three developmental periods: adolescence, young adulthood, and adulthood. A cross-lag model was used to examine the bidirectional model of marijuana and conventional cigarette smoking frequency from ages 13 to 33 years. The bidirectional model accounted for gender, school-age economic disadvantage, childhood attention problems, and race. Marijuana use and conventional cigarette smoking were associated within time in decreasing magnitude and increased cigarette smoking predicted increased marijuana use during adolescence. A reciprocal relationship was found in the transition from young adulthood to adulthood, such that increased conventional cigarette smoking at age 24 years uniquely predicted increased marijuana use at age 27 years, and increased marijuana use at age 24 years uniquely predicted more frequent conventional cigarette smoking at age 27 years, even after accounting for other factors. The association between marijuana and cigarette smoking was found to developmentally vary in the current study. Results suggest that conventional cigarette smoking prevention efforts in adolescence and young adulthood could potentially lower the public health impact of both conventional cigarette smoking and marijuana use. Findings point to the importance of universal conventional cigarette smoking prevention efforts among adolescents as a way to decrease later marijuana use and suggest that a prevention effort focused on young adults as they transition to adulthood would lower the use of both cigarette and marijuana use.
Preclinical studies of overlapping 15mer peptides, spanning SIV, SHIV or HIV, pulsed on autologous PBMC ex vivo have demonstrated high level, virus-specific T cell responses and viral suppression in ...non-human primates (NHP). Opal-HIV-Gag(c) consists of 120 synthetic 15mer peptides spanning Clade C, consensus Gag, manufactured to current good manufacturing practice; having been evaluated in a good laboratory practice toxicology study in Macaca mulatta. We evaluated the safety and preliminary immunogenicity of such peptides administered intravenously after short-duration ex vivo incubation, to HIV-positive adults on suppressive antiretroviral therapy.
A first-in-human, placebo-controlled, double-blind, dose escalation study was conducted. Twenty-three patients with virus suppressed by antiretroviral therapy were enrolled in four groups 12 mg (n = 6), 24 mg (n = 6), 48 mg (n = 2) or matching placebo (n = 8). Treatment was administered intravenously after bedside enrichment of 120 mL whole blood for white cells using a closed system (Sepax S-100 device), with ex vivo peptide admixture (or diluent alone) and 37°C incubation for one hour prior to reinfusion. Patients received 4 administrations at monthly intervals followed by a 12-week observation post-treatment. Opal-HIV-Gag(c) was reasonably tolerated at doses of 12 and 24 mg. There was an increased incidence of temporally associated pyrexia, chills, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c) recipients compared to placebo. The study was terminated early, after two patients were recruited to the 48 mg cohort; a serious adverse event of hypotension, tachycardia secondary to diarrhoea occurred following a single product administration. An infectious cause for the event could not be identified, leaving the possibility of immunologically mediated product reaction.
A serious, potentially life-threatening event of hypotension led to early, precautionary termination of the study. In the absence of a clearly defined mechanism or ability to predict such occurrence, further development of Opal-HIV-Gag(c) will not be undertaken in the current form.
ClinicalTrials.gov NCT01123915; EudraCT: 2008-005142-23.
ABSTRACT We present results from spectroscopic observations with the Michigan/Magellan Fiber System (M2FS) of 182 stellar targets along the line of sight (LOS) to the newly discovered "ultrafaint" ...object Reticulum 2 (Ret 2). For 37 of these targets, the spectra are sufficient to provide simultaneous estimates of LOS velocity ( , median random error km s−1), effective temperature ( , K), surface gravity ( , dex), and iron abundance ( , dex). We use these results to confirm 17 stars as members of Ret 2. From the member sample we estimate a velocity dispersion of km s−1 about a mean of km s−1 in the solar rest frame ( km s−1 in the Galactic rest frame), and a metallicity dispersion of dex about a mean of . These estimates marginalize over possible velocity and metallicity gradients, which are consistent with zero. Our results place Ret 2 on chemodynamical scaling relations followed by the Milky Way's dwarf-galactic satellites. Under assumptions of dynamic equilibrium and negligible contamination from binary stars-both of which must be checked with deeper imaging and repeat spectroscopic observations-the estimated velocity dispersion suggests a dynamical mass of enclosed within projected halflight radius pc, with mass-to-light ratio in solar units.
Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are ...retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least‐known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow‐up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p<0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis. (HEPATOLOGY 1994;19:1149–1156.)
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