Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value<0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value <0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.     

Rural residents' perspectives on the rural ‘good death’: a scoping review

The ‘good death’ is one objective of palliative care, with many ‘good death’ viewpoints and research findings reflecting the urban voice. Rural areas are distinct and need special consideration. This scoping review identified and charted current research knowledge on the ‘good’ rural death through the perspectives of rural residents, including rural patients with a life‐limiting illness, to identify evidence and gaps in the literature for future studies. A comprehensive literature search of English language articles (no date filter applied) was conducted in 2016 (2 January to 14 February) using five library databases. Reference lists of included articles, recent issues of eight relevant journals and three grey literature databases were also hand‐searched. Twenty articles (for 17 studies and one systematic review) were identified after a two‐phase screening process by two reviewers, using pre‐determined inclusion criteria. Data from each study were extracted and charted, analysed using a thematic analysis of the included articles' content, and with a quantitative analysis of the scoping review. These papers revealed data collected from rural patients with a life‐limiting illness and family caregivers, rural healthcare providers, the wider rural community, rural community leaders and rural health administrators and policy makers. Rural locations were heterogeneous. Residents from developed and developing countries believe a ‘good death’ is one that is peaceful, free of pain and without suffering; however, this is subjective and priorities are based on personal, cultural, social and religious perspectives. Currently, there is insufficient data to generalise rural residents' perspectives and what it means for them to die well. Given the extreme importance of a ‘good death’, there is a need for further studies to elicit rural patient and family caregiver perspectives.     

Adverse Childhood Experiences and Child Health Outcomes: Comparing Cumulative Risk and Latent Class Approaches

Objectives This study seeks to further the work exploring adverse childhood experiences (ACEs) by proposing a novel approach to understanding the impact of ACEs through applying advanced analytical methods to examine whether combinations of ACEs differentially impact child health outcomes. Methods Using National Survey of Children’s Health data, we use latent class analysis to estimate associations between classes of ACEs and child health outcomes. Results Class membership predicts child poor health, with differences found for specific ACE combinations. A subgroup of children exposed to poverty and parental mental illness are at higher risk for special healthcare needs than all other groups, including children exposed to 3 or more ACEs. Conclusions Different combinations of ACEs carry different risk for child health. Interventions tailored to specific ACEs and ACE combinations are likely to have a greater effect on improving child health. Our findings suggest children who experience specific ACE combinations (e.g., poverty and parental mental illness) are at particularly high risk for poor health outcomes. Therefore, clinicians should routinely assess for ACEs to identify children exposed to the most problematic ACE combinations; once identified, these children should be given priority for supportive interventions tailored to their specific ACE exposure and needs.     

Higher order aberrations,refractive error development and myopia control: a review

Evidence from animal and human studies suggests that ocular growth is influenced by visual experience. Reduced retinal image quality and imposed optical defocus result in predictable changes in axial eye growth. Higher order aberrations are optical imperfections of the eye that alter retinal image quality despite optimal correction of spherical defocus and astigmatism. Since higher order aberrations reduce retinal image quality and produce variations in optical vergence across the entrance pupil of the eye, they may provide optical signals that contribute to the regulation and modulation of eye growth and refractive error development. The magnitude and type of higher order aberrations vary with age, refractive error, and during near work and accommodation. Furthermore, distinctive changes in higher order aberrations occur with various myopia control treatments, including atropine, near addition spectacle lenses, orthokeratology and soft multifocal and dual-focus contact lenses. Several plausible mechanisms have been proposed by which higher order aberrations may influence axial eye growth, the development of refractive error, and the treatment effect of myopia control interventions. Future studies of higher order aberrations, particularly during childhood, accommodation, and treatment with myopia control interventions are required to further our understanding of their potential role in refractive error development and eye growth.     

Novel Tools to Improve Patient Selection and Monitoring on Active Surveillance for Low-risk Prostate Cancer: A Systematic Review

Context

Active surveillance (AS) is an alternative to initial radical treatment of low-risk prostate cancer (PCa). Current criteria for selection and follow-up incorrectly exclude some patients eligible for AS and misclassify some who actually harbour significant disease. Better prediction of cancer behaviour at diagnosis would allow less strict monitoring and may improve acceptance of AS.

Objective

To review and critically analyse the literature on the value of novel clinical tools for patient selection and monitoring on AS.

Evidence acquisition

A comprehensive search of the PubMed database until July 10, 2013, was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement guidelines. Studies assessing novel markers and diagnostics for patient selection for AS and follow-up during AS were included. Studies analysing only classic clinical parameters used in current protocols (prostate-specific antigen, prostate volume, number of (positive) prostate biopsies, percentage malignant tissue, Gleason score) were excluded. This review focuses only on the AS setting and not on predicting insignificant disease in general.

Evidence synthesis

Of 787 studies on AS, 30 were included in this review: 14 on magnetic resonance imaging (MRI), 5 on serum markers, 5 on urinary markers, 4 on histopathology markers, and 2 on germline genetic markers. Several of these markers improve the prediction of tumour volume, tumour grade, or time to active treatment. MRI has a high specificity for low-risk PCa; new serum markers are associated with unfavourable disease. In none of the studies was the new marker used as the primary decision tool. Long-term outcome measures such as mortality were not assessed. The definition of indolent PCa is disputable.

Conclusions

Imaging and serum markers may improve future patient selection for AS and follow-up during AS. Prospective studies should aim to further evaluate the clinical utility of these new markers with respect to longer term outcomes of AS.

Patient summary

We searched the literature for articles reporting new ways to safely monitor low-risk prostate cancer for patients who have not had radical treatment. We found 30 articles. The most promising tools appear to be magnetic resonance imaging scans and various new blood markers. These may be used in the future within active surveillance regimens.     

Comparative outcomes and cost-utility after surgical treatment of focal lumbar spinal stenosis compared with osteoarthritis of the hip or knee—part 1: long-term change in health-related quality of life

Background contextIt is well accepted that total hip and knee arthroplasty (THA/TKA) for osteoarthritis (OA) is associated with reliable and sustained improvements in postoperative health-related quality of life (HRQoL). Although several studies have demonstrated comparable outcomes with THA/TKA after surgical intervention for lumbar spinal stenosis (LSS), the sustainability of the outcome after LSS surgery compared with THA/TKA remains uncertain.PurposeThe primary purpose of this study is to assess whether improvements in HRQoL after surgical management of focal lumbar spinal stenosis (FLSS) with or without spondylolisthesis are sustainable over the long term compared with that of THA/TKA for OA.Study designSingle-center, retrospective, longitudinal matched cohort study of prospectively collected outcomes, with a minimum of 5-year follow-up (FU).Patient samplePatients who had primary one- to two-level spinal decompression with or without instrumented fusion for FLSS and THA/TKA for primary OA.Outcome measuresPostoperative change from baseline to last FU in Short-Form 36 physical component summary (PCS) and mental component summary (MCS) scores among groups was used as the primary outcome measure.MethodsAn age, sex-matched inception cohort of primary one- to two-level spinal decompression with or without instrumented fusion for FLSS (n=99) was compared with a cohort of primary THA (n=99) and TKA (n=99) for OA and followed for a minimum of 5 years. Linear regression was used for the primary analysis.ResultsMean (percent) FUs in months were 80.5+16.04 (79%), 94.6+16.62 (92%), and 80.6+16.84 (85%) for the FLSS, THA, and TKA cohorts, respectively, with a range of 5 to 10 years for all three cohorts. The number of patients who have undergone revision including those lost to FU for the FLSS, THA, and TKA cohorts were n=20 (20.2%, same site [n=7] and adjacent segment [n=13]) requiring 27 operations, n=3 (3%, same site) requiring 5 operations, and n=8 (8.1%, same site) requiring 12 operations, respectively (p<.01). The average time to first revision was 56/65/43 months, respectively. Mean postoperative PCS (p<.0001) and MCS (p<.02) scores improved significantly and were durable for all groups at the last FU. The mean changes from baseline PCS/MCS scores to last FU were 8.5/6.4, 12.3/7.0, and 8.3/4.9 for FLSS, THA, and TKA, respectively. Adjusting for baseline age, sex, body mass index, PCS score, and MCS score, there was a strong trend in favor of greater sustained change in the PCS score of THA over FLSS (p=.07) and TKA (p=.08). No difference was noted for change in PCS score between FLSS and TKA (p=.95). No differences were noted for change in MCS score among all three cohorts (p>.1).ConclusionsSignificant improvements in HRQoL after surgical treatment of FLSS with or without spondylolisthesis and hip and knee OA are sustained for a mean of 7 to 8 years, with a minimum of 5-year FU. Despite a higher revision rate, patients undergoing surgery for FLSS can expect a comparable long-term average improvement in HRQoL from baseline compared with their peers undergoing TKA and to a lesser extent THA.