Notes

Cost-effective clinical study design and style: Using the Bayesian step by step model to the ProFHER realistic tryout.
f bias. This convergent validity supports use of both tools for the purpose of assessing risk of bias and selecting studies that report prevalence for inclusion in economic analyses.
To examine surgical outcomes and trends in the implementation of minimally invasive surgery (MIS) use for endometrial cancer (EC).

Retrospective cohort study.

English National Health Service hospitals 2011-2017/2018.

35 304 patients having a hysterectomy for EC identified from Hospital Episode Statistics.

Univariate and multivariate analyses compared MIS to open hysterectomy (OH) by assessing the association between demographic, clinical and hospital characteristics by using logistic regression. A propensity score was created, to control for confounding factors including demographics, clinical and hospital characteristics, from a logistic regression which enabled the inverse probability weighting of treatment to be applied in order to compare outcomes of treatment.

The association between route of surgery on perioperative morbidity and mortality.

The MIS rate rose from 40.3% in 2011 to 68.7% in 2017/2018, however, there was significant geographical variation (p<0.001). The overall 90-day mortality was significantly higher with OH versus MIS (OR 0.34, 95% CI 0.18 to 0.62, p=0.0002). MIS rates were significantly lower in patients from the lowest socioeconomic group (LSEG) compared with patients from the highest group (HSEG) (55.4% vs 59.9%, p<0.01), and in the black population as compared with white and Asian populations (40.4% vs 58.6% and 56.0%, p<0.0001). When patients from LSEG and black patients were treated in hospitals with high MIS rates, the MIS rate increased close to that of the HSEG and white patients (81.0% and 74.1% vs 83.2% and 82.6%).

Further investigation is needed to understand the barriers to MIS and improve access so that as many patients as possible can benefit from the reduced morbidity/mortality associated with MIS.
Further investigation is needed to understand the barriers to MIS and improve access so that as many patients as possible can benefit from the reduced morbidity/mortality associated with MIS.
To systematically review qualitative studies reporting the use of virtual consultations within an orthopaedic rehabilitation setting and to understand how its use changes the work required of patients.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement, we conducted a systematic review of papers to answer the research question 'How do changes in the work of being a patient when using communication technology influence patient preferences?' Electronic databases were searched for studies meeting the inclusion criteria in April 2020.

The search strategy identified 2057 research articles from the database search. A review of titles and abstracts using the inclusion criteria yielded 21 articles for full-text review. Nine studies were included in the final analysis. Six studies explored real-time video conferencing and three explored telephone consultations. The use of communication technology changes the work required of patients. Such changes will impact on expectations for care, resources required of patients, the environment of receiving care and patient-clinician interactions. This adjustment of the work required of patients who access orthopaedic rehabilitation using communication technology will impact on their experience of receiving care. It is proposed that changes in the work of being a patient will influence preferences for or against the use of communication technology consultations for orthopaedic rehabilitation.

We found that the use of communication technology changes the work of being a patient. The change in work required of patients can be both burdensome (it makes it harder for patients to access their care) and beneficial (it makes it easier for patients to access their care). This change will likely to influence preferences. Keeping the concept of patient work at the heart of pathway redesign is likely to be a key consideration to ensure successful implementation.

CRD42018100896.
CRD42018100896.
We assessed the impact of political conflict (Boko Haram) on tuberculosis (TB) case notifications in Adamawa State in North-east Nigeria.

A retrospective analysis of TB case notifications from TB registers (2010-2016) to describe changes in TB notification, sex and age ratios by the degree of conflict by local government area.

Adamawa State.

21 076 TB cases notified.

21 076 cases (62% male) were notified between 2010 and 2016, of which 19 604 (93%) were new TB cases. Areas affected by conflict in 2014 and 2015 had decreased case notification while neighbouring areas reported increased case notifications. The male to female ratio of TB cases changed in areas in conflict with more female cases being notified. The young and elderly (1-14 and >65 years old) had low notifications in all areas, with a small increase in case notifications during the years of conflict.

TB case notifications decreased in conflict areas and increased in areas without conflict. More males were notified during peace times and more female cases were reported from areas in conflict. Young and elderly populations had decreased case notifications but experienced a slight increase during the conflict years. These changes are likely to reflect population displacement and a dissimilar effect of conflict on the accessibility of services. TB services in conflict areas deserve further study to identify resilient approaches that could reach affected populations.
TB case notifications decreased in conflict areas and increased in areas without conflict. More males were notified during peace times and more female cases were reported from areas in conflict. Young and elderly populations had decreased case notifications but experienced a slight increase during the conflict years. These changes are likely to reflect population displacement and a dissimilar effect of conflict on the accessibility of services. TB services in conflict areas deserve further study to identify resilient approaches that could reach affected populations.
Obstacles to successful settlement-social isolation, language hardship, issues with employment, housing questions, transportation, barriers to health, education and government service access-all potentially play a role in emerging physical and mental health problems. The objective of this scoping review is to map the available evidence in order to provide an overview of the services and resources offered to refugees, immigrants and other newcomers by settlement agencies to support emotional wellness and well-being.

The protocol to be followed for this scoping review is based on the Joanna Briggs Institute to provide a map of the current and emergent literature, and examine the extent, range and nature of this literature. The proposed scoping review will also identify the gaps in research pertaining to the emotional wellness of refugees, immigrants and other newcomers as well as summarise and disseminate research findings and provide direction for future reviews. Key databases for this scoping review incluarch will not involve human or animal subjects. The research is a scoping review, and thus relies on published and grey literature studies and documents. The findings of this proposed scoping review will be disseminated through future publications as well as presentations to relevant stakeholders, including immigrant serving agencies. We anticipate that this scoping review will identify gaps in research pertaining to the emotional wellness of refugees, immigrants and other newcomers. The results of this review will be the first comprehensive recent survey of emotional wellness practices employed by settlement agencies.Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells. NGI-1, which inhibits B7-H4 glycosylation causing its ubiquitination and subsequent degradation, improves the immunogenic properties of cancer cells treated with doxorubicin, enhancing their phagocytosis by dendritic cells and their capacity to elicit CD8+ IFNγ-producing T-cell responses. In preclinical models of TNBC, a triple combination of NGI-1, camsirubicin (a noncardiotoxic doxorubicin analogue) and PD-L1 blockade was effective in reducing tumor growth. read more Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule B7-H4. SIGNIFICANCE This work unravels the regulation of B7-H4 stability by ubiquitination and glycosylation, which affects tumor immunogenicity, particularly regarding immune-cold breast cancers. The inhibition of B7-H4 glycosylation can be favorably combined with immunogenic chemotherapy and PD-L1 blockade to achieve superior immuno-infiltration of cold tumors, as well as improved tumor growth control.See related commentary by Pearce and Läubli, p. 1789.This article is highlighted in the In This Issue feature, p. 1775.Epigenetic allele diversity is linked to inferior prognosis in acute myeloid leukemia (AML). However, the source of epiallele heterogeneity in AML is unknown. Herein we analyzed epiallele diversity in a genetically and clinically annotated AML cohort. Notably, AML driver mutations linked to transcription factors and favorable outcome are associated with epigenetic destabilization in a defined set of susceptible loci. In contrast, AML subtypes linked to inferior prognosis manifest greater abundance and highly stochastic epiallele patterning. We report an epiallele outcome classifier supporting the link between epigenetic diversity and treatment failure. Mouse models with TET2 or IDH2 mutations show that epiallele diversity is especially strongly induced by IDH mutations, precedes transformation to AML, and is enhanced by cooperation between somatic mutations. Furthermore, epiallele complexity was partially reversed by epigenetic therapies in AML driven by TET2/IDH2, suggesting that epigenetic therapy might function in part by reducing population complexity and fitness of AMLs. SIGNIFICANCE We show for the first time that epigenetic clonality is directly linked to specific mutations and that epigenetic allele diversity precedes and potentially contributes to malignant transformation. Furthermore, epigenetic clonality is reversible with epigenetic therapy agents.This article is highlighted in the In This Issue feature, p. 1775.Lung cancer researcher Solange Peters, MD, PhD, discusses the intersection of COVID-19 and cancer, as well as her research on immunotherapy biomarkers.
Ulcerative colitis (UC) is a lifelong, relapsing-remitting disease. Patients non-responsive to pharmacological treatment may require a colectomy. We estimated pre-colectomy and post-colectomy healthcare resource utilisation (HCRU) and costs in England.

A retrospective, longitudinal cohort study indexing adult patients with UC undergoing colectomy (2009-2015), using linked Clinical Practice Research Datalink/Hospital Episode Statistics data, was conducted. HCRU, healthcare costs and pharmacological treatments were evaluated during 12 months prior to and including colectomy (baseline) and 24 months post-colectomy (follow-up; F-U), comparing baseline/F-U, emergency/elective colectomy and subtotal/full colectomy using descriptive statistics and paired/unpaired tests.

249 patients from 26 165 identified were analysed including 145 (58%) elective and 184 (74%) full colectomies. Number/cost of general practitioner consultations increased post-colectomy (p<0.001), and then decreased at 13-24 months (p<0.05).
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