Background Antiretroviral therapy (ART), when taken consistently, reduces morbidity and mortality associated with human immunodeficiency virus and viral transmission. Suboptimal treatment adherence is associated with regimen complexity and high tablet burden. Single-tablet regimens (STRs) provide a complete treatment regimen in a single tablet. This study examined the relationship between STRs (vs multiple-tablet regimens [MTRs]), treatment adherence, and viral suppression. Methods A systematic review was conducted to identify studies investigating at least one of the following: (1) STR/MTR use and adherence; (2) levels of adherence and viral suppression; and (3) STR/MTR use and viral suppression. Meta-analysis was performed to assess the relationship between STR vs MTR use and adherence in observational settings at ≥95% and ≥90% adherence thresholds. Results In total, 29 studies were identified across the three objectives; two studies were relevant for all objectives. STRs were associated with higher treatment adherence than MTRs in 10/11 observational studies: a 63% greater likelihood of achieving ≥95% adherence (95% CI=1.52–1.74; P <0.001) and a 43% increase in the likelihood of achieving ≥90% adherence (95% CI=1.21–1.69; P <0.001). Higher adherence rates were associated with higher levels of viral suppression in 13/18 studies. Results were mixed in five studies investigating the association between STR or MTR use and viral suppression. Conclusion Although the direct effect of STRs vs MTRs on viral suppression remains unclear, this study provided a quantitative estimate of the relationship between STRs and ART adherence, demonstrating that STRs are associated with significantly higher ART adherence levels at 95% and 90% thresholds. Findings from the systematic review showed that improved adherence results in an increased likelihood of achieving viral suppression in observational settings. Future research should utilize similar measures for adherence and evaluate viral suppression to improve assessment of the relationship between pill burden, adherence, and viral suppression.

The inhibitory effect of androgens on the hypothalamic-pituitary-adrenal (HPA) axis in basal and stress conditions in adult male rats is well documented. Major sex-related neuroendocrine changes take place during puberty. There is a robust rise in production and secretion of gonadal steroids, which is thought to underlie numerous neural and behavioural changes brought on after puberty. The present study investigated the effect of the pubertal rise in gonadal steroid levels on the subsequent adult corticosterone profile, particularly the sensitivity of the adult HPA axis to testosterone. Animals were castrated either prepubertally (28 days) or in adulthood (11 weeks) and adult animals were subsequently treated with subcutaneous implants containing either testosterone or cholesterol. Using an automated blood sampling system, blood was collected from each freely moving, conscious rat every 10 min (i) over a 24 h period; (ii) in response to 10 min of noise stress, and (iii) following an immunological challenge with lipopolysaccharide (LPS). Analysis revealed that testosterone treatment did not significantly affect overall corticosterone release over the 24 h period in adult animals castrated before puberty in contrast to animals castrated in adulthood in which testosterone significantly suppressed corticosterone secretion. Following either a noise stress or LPS injection, testosterone treatment did not affect the hypothalamic or adrenal stress response in animals castrated prepubertally. Testosterone significantly suppressed the corticotrophin-releasing hormone and arginine vasopressin mRNA as well as the corticosterone response to LPS in castrated animals that had had their testes intact over puberty. These data provide evidence that puberty is a critical organizational period during which rising levels of gonadal steroids programme the sensitivity of the adult HPA axis to gonadal steroids in adulthood.

The neuroendocrine gender dimorphism that begins during perinatal development is completed during puberty. We have previously described how the perinatal gonadal steroids programme hypothalamic-pituitary-adrenal (HPA) activity in adulthood and we now assess the role of peripubertal ovarian hormones. Prepubertal females were treated subcutaneously with either cholesterol or 17b-oestradiol and their pituitary-adrenal activity was assessed 5 days later. Oestradiol suppressed the ACTH and corticosterone responses to restraint stress in the prepubertal female. Furthermore, groups of female rats were ovariectomised (OVX) either before or after puberty and adult animals were subsequently treated with subcutaneous implants containing either 17b-oestradiol or cholesterol. Corticosterone pulsatility was assessed using an automated blood sampling system to collect blood from freely moving animals at 10 min intervals over 24 h. Oestradiol administered to adults that had been OVX either pre-or postpubertally displayed a significantly higher mean corticosterone level as well as increased pulse frequency and pulse amplitude compared with cholesterol treated controls. These data demonstrate a reversal in the effect of oestrogens on HPA axis activity over the time of puberty with inhibitory effects prepubertally and stimulatory actions after puberty and imply an ovarian steroid-independent mechanism of pubertal maturation of HPA sensitivity to oestrogens.

Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation.

Background Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. Methods A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a ‘good–moderate–poor’ rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. Results A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. Conclusions The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.