Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise for treating cancers with homologous recombination (HR) defects, such as germline BRCA1/2 mutation. Further studies suggest that PARP inhibitors (PARPi) can also exhibit efficacy in HR-competent cancers, by amplifying the DNA damage and inducing immunogenic cell death, and PARPi lead to increasing tumor neoantigen, upregulation of interferons and PD-L1, and modulation of the tumor microenvironment, which may facilitate a more profound antitumor immune response. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have achieved impressive success in the treatment of different malignancies. However, only a subset of populations derive clinical benefit, and the biomarkers and resistance mechanisms are not fully understood. Therefore, given that PARPi could potentiate the therapeutic effect of ICIs, PARPi combined with ICIs are becoming an alternative for patients who cannot benefit from ICI monotherapy. In this review, we focus on the mechanisms and immune role of PARPi and discuss the rationale and clinical studies of this combined regimen.

The increasing prioritisation of healthcare quality across the six domains of efficiency, safety, patient-centredness, effectiveness, timeliness and accessibility has given rise to accelerated change both in the uptake of initiatives and the realisation of their outcomes to meet external targets. Whilst a multitude of change management methodologies exist, their application in complex healthcare contexts remains unclear. Our review sought to establish the methodologies applied, and the nature and effectiveness of their application in the context of healthcare.

A systematic review and narrative synthesis was undertaken. Two reviewers independently screened the titles and abstracts followed by the full-text articles that were potentially relevant against the inclusion criteria. An appraisal of methodological and reporting quality of the included studies was also conducted by two further reviewers.

Thirty-eight studies were included that reported the use of 12 change management methodologies in healthcare ciple to underpin a change in complex healthcare contexts. The lack of prescription application of the change management methodologies was identified. Change management methodologies were valued for providing guiding principles for change that are well suited to enable methodologies to be applied in the context of complex and unique healthcare contexts, and to be used in synergy with implementation and improvement methodologies.

Retinal layer thickness parameters measured by optical coherence tomography (OCT) are emerging biomarkers of neuroaxonal degeneration and inflammation in multiple sclerosis (MS). We aimed to evaluate the value of retinal layer thickness for prediction of disability worsening and relapse in a real-world MS cohort.

For this longitudinal observational study, we included MS patients with spectral-domain OCT scans available and ≥1 year of clinical follow-up. The value of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion-cell-and-inner-plexiform-layer (GCIPL) and inner nuclear layer (INL) thickness for prediction of disability worsening and relapse during the observation period was tested by multivariate models.

We analyzed 60 MS patients during a mean observation period of 2.9 years (SD 1.8). Lower baseline thickness of GCIPL (cut-off <77µm; HR 4.1, p=0.001) and pRNFL (cut-off ≤88µm; HR 3.1, p=0.019) were associated with an increased risk of disability worsening. Longitudinally, mean thinning rates were -0.8µm/year (SD 1.6) for GCIPL, -0.6µm/year (SD 3.5) for pRNFL. GCIPL thinning ≥1.0µm/year and pRNFL >1.5µm/year is associated with higher likelihood of disability worsening (HR 5.7, p=0.009 and HR 6.8, p=0.003, respectively). GSK J1 INL thickened in patients with relapse by a mean 0.9µm while thinning by 0.3µm in patients without relapse (p=0.04). In multivariate analyses, INL thickening was associated with an increased probability of relapse (OR 17.8, p=0.023).

Cross-sectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Change of INL thickness is a promising marker of relapse, i.e. inflammatory activity.

Cross-sectional and longitudinal measurement of GCIPL and pRNFL thinning is reliable as a biomarker of disability worsening in a real-world setting. Change of INL thickness is a promising marker of relapse, i.e. inflammatory activity.

Blood transfusion is a conventional therapeutic procedure; however, the perceptions of general public and healthcare professionals (HCPs), especially physicians and nurses, remain unclear, although the insights of HSPs may affect the treatment decision. This study aimed to assess the awareness of HCPs and the public about blood transfusion risks and consent in Qassim region of Saudi Arabia, to uncover the factors that may influence such perceptions.

This study used two different closed questionnaires that were distributed electronically between February and March 2018 among the population and HCPs in Qassim region.

A total of 400 general public participants and 135 HCPs completed the survey. Among the surveyed participants, 70% believed that blood transfusion therapy was safe. The perceived risk of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) was the highest among all complications (74%). Furthermore, 88.2% of respondents were willing to accept a blood transfusion as a therapeutic measure, primarily from a first-degree relative, although the remaining 11.8% rejected the idea of a transfusion due to fear of medical error. From the HCP survey, 80% were previously involved in a blood transfusion therapy consent process. HCPs typically reported explaining the benefits, risks, and alternatives described in the consent form (74.1%, 67.4%, and 53.3%, respectively).

Our results indicated that despite the current high level of acceptance and knowledge regarding blood transfusions, additional educational efforts remain necessary to increase public awareness of blood transfusion therapy.

Our results indicated that despite the current high level of acceptance and knowledge regarding blood transfusions, additional educational efforts remain necessary to increase public awareness of blood transfusion therapy.