Safety, Immunogenicity and Duration of Protection of the RTS,S/AS02D Malaria Vaccine: One Year Follow-Up of a Randomized Controlled Phase I/IIb Trial

The RTS,S/AS02(D) vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants.We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02(D) given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6-79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02(D) and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02(D), remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: -4.3-56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1-88.2, p = 0.003).The RTS,S/AS02(D) malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time.ClinicalTrials.gov NCT00197028

A systematic review on the effectiveness of complementary and alternative medicine for chronic non-specific low-back pain

The purpose of this systematic review was to assess the effects of spinal manipulative therapy (SMT), acupuncture and herbal medicine for chronic non-specific LBP. A comprehensive search was conducted by an experienced librarian from the Cochrane Back Review Group (CBRG) in multiple databases up to December 22, 2008. Randomised controlled trials (RCTs) of adults with chronic non-specific LBP, which evaluated at least one clinically relevant, patient-centred outcome measure were included. Two authors working independently from one another assessed the risk of bias using the criteria recommended by the CBRG and extracted the data. The data were pooled when clinically homogeneous and statistically possible or were otherwise qualitatively described. GRADE was used to determine the quality of the evidence. In total, 35 RCTs (8 SMT, 20 acupuncture, 7 herbal medicine), which examined 8,298 patients, fulfilled the inclusion criteria. Approximately half of these (2 SMT, 8 acupuncture, 7 herbal medicine) were thought to have a low risk of bias. In general, the pooled effects for the studied interventions demonstrated short-term relief or improvement only. The lack of studies with a low-risk of bias, especially in regard to SMT precludes any strong conclusions; however, the principal findings, which are based upon low- to very-low-quality evidence, suggest that SMT does not provide a more clinically beneficial effect compared with sham, passive modalities or any other intervention for treatment of chronic low-back pain. There is evidence, however, that acupuncture provides a short-term clinically relevant effect when compared with a waiting list control or when acupuncture is added to another intervention. Although there are some good results for individual herbal medicines in short-term individual trials, the lack of homogeneity across studies did not allow for a pooled estimate of the effect. In general, these results are in agreement with other recent systematic reviews on SMT, but in contrast with others. These results are also in agreement with recent reviews on acupuncture and herbal medicine. Randomized trials with a low risk of bias and adequate sample sizes are direly needed

Influence of antisynthetase antibodies specificities on antisynthetase syndrome clinical spectrum time course

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition

Massage Therapy for Osteoarthritis of the Knee: A Randomized Dose-Finding Trial

In a previous trial of massage for osteoarthritis (OA) of the knee, we demonstrated feasibility, safety and possible efficacy, with benefits that persisted at least 8 weeks beyond treatment termination.We performed a RCT to identify the optimal dose of massage within an 8-week treatment regimen and to further examine durability of response. Participants were 125 adults with OA of the knee, randomized to one of four 8-week regimens of a standardized Swedish massage regimen (30 or 60 min weekly or biweekly) or to a Usual Care control. Outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog pain scale, range of motion, and time to walk 50 feet, assessed at baseline, 8-, 16-, and 24-weeks.WOMAC Global scores improved significantly (24.0 points, 95% CI ranged from 15.3-32.7) in the 60-minute massage groups compared to Usual Care (6.3 points, 95% CI 0.1-12.8) at the primary endpoint of 8-weeks. WOMAC subscales of pain and functionality, as well as the visual analog pain scale also demonstrated significant improvements in the 60-minute doses compared to usual care. No significant differences were seen in range of motion at 8-weeks, and no significant effects were seen in any outcome measure at 24-weeks compared to usual care. A dose-response curve based on WOMAC Global scores shows increasing effect with greater total time of massage, but with a plateau at the 60-minute/week dose.Given the superior convenience of a once-weekly protocol, cost savings, and consistency with a typical real-world massage protocol, the 60-minute once weekly dose was determined to be optimal, establishing a standard for future trials.ClinicalTrials.gov NCT00970008

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies

Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern

Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01(E) and RTS,S/AS02(D). Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2(+) CD4(+) T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01(E) and RTS,S/AS02(D) induced adaptive immune responses including antibodies, circulating memory B cells and CD4(+) T cells directed against P. falciparum CS protein.ClinicalTrials.gov NCT00307021

Self-control interventions for children under age 10 for improving self-control and delinquency and problem behaviors

Self-control improvement programs are intended to serve many purposes, most notably improving self-control. Yet, interventions such as these often aim to reduce delinquency and problem behaviors. However, there is currently no summary statement available regarding whether or not these programs are effective in improving self-control and reducing delinquency and problem behaviors. The main objective of this review is to assess the available research evidence on the effect of self-control improvement programs on self-control and delinquency and problem behaviors. In addition to investigating the overall effect of early selfcontrol improvement programs, this review will examine, to the extent possible, the context in which these programs may be most successful. The studies included in this systematic review indicate that self-control improvement programs are an effective intervention for improving self-control and reducing delinquency and problem behaviors, and that the effect of these programs appears to be rather robust across various weighting procedures, and across context, outcome source, and based on both published and unpublished data

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions.

BACKGROUND: Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world's population need a prosthesis or orthosis. OBJECTIVE: The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. METHODS: Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. RESULTS: A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. CONCLUSIONS: At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness

Registration of ‘LCS Compass’ Wheat

‘LCS Compass’ (Reg. No. CV-1149, PI 675458), a hard red winter (HRW) wheat (Triticum aestivum L.), was developed and tested as VA10HRW-13 and co-released by the Virginia Agricultural Experiment Station and Limagrain Cereal Seeds, LLC, in 2015. LCS Compass was derived from the cross ‘Vision 20’ /‘Stanof’ using a modified bulk breeding method. LCS Compass is a widely adapted, high-yielding, awned, semidwarf (Rht1) HRW wheat with early to medium maturity and resistance or moderate resistance to diseases prevalent in the mid-Atlantic and Great Plains regions of the United States. In the 2013 Uniform Bread Wheat Trial conducted over 18 locations in eastern states, LCS Compass produced an average grain yield of 4609 kg ha−1 that was similar to ‘Vision 30’ (4697 kg ha−1). In the northern Great Plains, the average grain yield of LCS Compass (4015 kg ha−1) over 44 locations in 2013 was similar to ‘Jerry’ (4013 kg ha−1). In the South Dakota crop zone 3 variety test, LCS Compass had a 3-yr (2015–2017) yield average of 5575 kg ha−1 and was one of highest-yielding cultivars among the 19 cultivars tested over the 3-yr period. LCS Compass has good end-use quality in both the eastern and Great Plains regions of the United States