Immediate sequential bilateral cataract surgery: patient perceptions and preferences.

BACKGROUND: Recent national data suggests that less than 0.5% of NHS cataract patients undergo immediate sequential bilateral cataract surgery (ISBCS). Since ISBCS improves service efficiency, increasing its practice may help tackle the ever-growing burden of cataract in the UK, and reduce the COVID-19 cataract backlog. Surgeon attitudes are known to be a significant barrier to increasing the practice of ISBCS. However, little is known about patient perceptions of ISBCS. METHODS: Patients at cataract clinics across three NHS hospital sites were recruited to complete an investigator-led structured questionnaire. Open-ended and closed-ended questions were used to assess awareness of ISBCS, willingness to undergo ISBCS and attitudes towards ISBCS. RESULTS: Questionnaires were completed by 183 patients. Mean participant age was 70.5 (9.9) years and 58% were female. Forty-three percent were aware of ISBCS, chiefly via clinic staff. Just over a third would choose ISBCS if given the choice, and participants that perceived they were recommended ISBCS were more likely to opt for it. The most common motivator and barrier to uptake of ISBCS was convenience and the perceived risk of complications in both eyes respectively. Concerns related to the recovery period were common, including misunderstandings, such as the need to wear eye patches that obscure both eyes. CONCLUSIONS: Our study indicates that significantly more NHS patients would be willing to undergo ISBCS if given the choice. The reluctance of surgeons to recommend ISBCS and patient misunderstandings regarding the recovery period may be limiting its uptake.

Palliative and End-of-Life Care Self-perceived Educational Needs of Physicians and Nurses in Rwanda.

Palliative care access is an urgent and ethical imperative to effectively manage the increasing burden of serious health-related suffering worldwide. Understanding the palliative care educational needs of health care professionals is critical to support evidence-based clinical practice in Rwanda and other low- and middle-income countries. A cross-sectional study was conducted at 5 hospitals in Kigali, Rwanda, to assess the palliative/end-of-life educational needs of nurses and physicians. The End-of-Life Professional Caregiver Survey and a demographic form were used to collect data. Descriptive analyses and independent t tests were conducted. A total of 420 health care professionals participated in the study (response rate, 72%). Participants perceived their knowledge and skills in providing palliative/end-of-life care as low. Those who received palliative/end-of-life care training in the past 5 years, third- and fourth-year residents, and health care providers with 5 years of experience or more had significantly higher (P ≤ .05) mean scores on the End-of-Life Professional Caregiver Survey. Nurses scored higher than physicians in the patient- and family-centered communication (P = .049) and cultural and ethical values (P = .037) subscales. Pain management was identified as an educational need by 77% of participants. Our survey suggests the need for increased governmental investments in palliative/end-of-life care education among nurses and physicians in Rwanda.

The Role of Nurses and Midwives in Expanding and Sustaining Voluntary Medical Male Circumcision Services for HIV Prevention: A Systematic and Policy Review.

ABSTRACT: Male circumcision reduces men's risk of acquiring HIV through heterosexual sex, and voluntary medical male circumcision (VMMC) is central to HIV prevention strategies in 15 sub-Saharan African countries. Nurses have emerged as primary VMMC providers; however, barriers remain to institutionalizing nurse-led VMMC. Patient safety concerns have hindered task sharing, and regulations governing nurse-performed VMMC are not always supportive or clear. We performed a systematic review on VMMC safety by provider cadre and a desk review of national policies governing the VMMC roles of nurses and midwives. Also, VMMC by nurses is safe and has become standard practice. Countries had multiple policy combinations among different documents, with only one disallowing VMMC by these cadres. Countries with alignment between policies often ensured that nursing workforces were equipped with clinical competencies through national certification. Regulatory clarity and formalized certification for nurse-performed VMMC can increase program sustainability and build nursing capacity to meet other critical basic surgical needs.

Long-term follow-up of phacotrabeculectomy surgery in Tanzania.

INTRODUCTION: The glaucomas often co-exist with cataract. We previously reported a large trial of anti-scarring treatment in combined phacotrabeculectomy surgery. Long-term outcomes in an African population are extremely rarely reported. We present here the outcomes in IOP, acuity, bleb morphology and patient perceptions at 3-5-years post surgery. METHODS: Tanzanian patients with glaucoma and visually significant cataract underwent combined phacotrabeculectomy surgery. In November 2015 an attempt was made to contact all participants in the study inviting them for a repeat examination. All who attended were given a detailed examination. A semi-structured interview in Swahili was administrated to determine patient experience and satisfaction with the surgery. RESULTS: Sixty-eight (23%) attended for repeat review in 2015. The mean time from original surgery was 4.5-years (range 2.3-6.6-years). Overall 53 (78%) had IOP < 21 mm Hg and 29 (43%) an IOP < 16 mm Hg at final follow-up. A flat bleb at 26 and 100 days was associated with failure by IOP criteria at 4.5-years post-operatively. A vascular bleb at those time points was not any more associated with late failure than a non-vascular bleb. A majority of patients were pleased with the surgery. The cost of surgery is high but it is a price patients were willing to pay. Nearly all patients (95%) would recommend the service to family and friends. DISCUSSION: Owing to the small proportion reviewed, our conclusions are severely limited. Phacotrabeculectomy worked well in a majority of the reviewed population long-term and is accepted by a majority of these patients as worthwhile.

Glaucoma Control Strategies in Sub-Saharan Africa: A Review of the Clinical and Health Economic Evidence.

PURPOSE: A review of the effectiveness, costs, and cost-effectiveness of detection and treatment strategies for glaucoma control in Sub-Saharan Africa (SSA) was conducted. METHODS: Detailed searches were performed using the Ovid Medline, Ovid Embase, The Cochrane Library, Web of Science, Scopus, and LILACS databases up to September 2016. The key Medical Subject Heading search terms used included glaucoma, diagnosis, treatment, effectiveness, costs, cost-effectiveness, and Sub-Saharan Africa. Effectiveness was measured as the proportion of study participants with an intra-ocular pressure less than or equal to 22 mmHg. RESULTS: A total of 5658 records were examined with 48 papers identified. The sensitivity and specificity of portable instruments or smartphone technologies to detect glaucomatous changes ranged from 58.3% to 93.8% and from 82.4% to 96.8%, respectively. The overall effect size for various glaucoma interventions was: 0.39 (95% confidence interval (CI) 0.27-0.54, I2 = 64.85, p = 0.036) for laser trabeculoplasty; 0.56 (95% CI 0.23-0.84, I2 = 85.74, p = 0.001) for drainage implant devices; 0.66 (95% CI 0.61-0.71, I2 = 0.00, p = 0.402) for medical management; and 0.73 (95% CI 0.65-0.80, I2 = 93.25, p = 0.000) for all other non-drainage tube surgical interventions, including trabeculectomy surgery and the use of anti-metabolites. The mean annual cost of anti-glaucoma drugs across SSA was USD 394, with a mean direct non-medication cost per year of USD 54, and a mean surgical cost per year of USD 283. CONCLUSIONS: While effective glaucoma control interventions exist, their widespread use and diffusion across SSA remain challenging principally due to low per capita income levels and high glaucoma treatment costs.

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer.

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

How do people interpret information about colorectal cancer screening: observations from a think-aloud study.

BACKGROUND: The English NHS Bowel Cancer Screening Programme biennially invites individuals aged 60-74 to participate in screening. The booklet, 'Bowel Cancer Screening: The Facts' accompanies this invitation. Its primary aim is to inform potential participants about the aims, advantages and disadvantages of colorectal cancer screening. OBJECTIVE: To provide detailed commentary on how individuals process the information contained within 'The Facts' booklet. DESIGN, SETTING AND PARTICIPANTS: This study comprised of 18 interviews with individuals aged 45-60 and used a 'think-aloud' paradigm in which participants read aloud the booklet. Participant utterances (verbal statements made in response to researcher-led prompts) were transcribed and analysed using a combination of content and thematic analysis. RESULTS: A total of 776 coded utterances were analysed (mean = 43.1 per person; range = 8-95). While overall comprehension was satisfactory, several problem areas were identified such as the use of complex unfamiliar terminology and the presentation of numerical information. Specific sections such as colonoscopy risk information evoked negative emotional responses. Participants made several suggestions for ways in which comprehension might be improved. CONCLUSION: Public perceptions of the NHS Bowel Cancer Screening Programme information materials indicated that specific aspects of the booklet were difficult to process. These materials may be an appropriate target to improve public understanding of the aims, benefits and disadvantages of colorectal cancer screening. These findings will contribute to a broader NIHR-funded project that aims to design a supplementary 'gist-based' information leaflet suitable for low literacy populations.

A mathematical model predicts that calreticulin interacts with the endoplasmic reticulum Ca(2+)-ATPase.

A robust mathematical model developed from single cell calcium (Ca(2+)) dynamics has enabled us to predict the consequences of over-expression of endoplasmic reticulum-located chaperones. Model predictions concluded that calreticulin interacts with the lumenal domain of the sarcoplasmic and endoplasmic reticulum Ca(2+)-activated ATPase (SERCA) pump, altering pump affinity for Ca(2+) (K(1/2) switches from 247 to 431 nM) and hence generating Ca(2+) oscillations. Expression of calreticulin in the ER generated an average of six transient-decline oscillations during the Ca(2+) recovery phase, upon exposure to maximal levels of the agonist ATP. In contrast, normal cells produced a single Ca(2+) transient with few or no oscillations. By conditioning the model to experimental data, parameters for generation and decay of IP(3) and SERCA pump kinetics were determined. To elucidate the possible source of the oscillatory behavior three possible oscillators, 1) IP(3), 2) IP(3)R, and 3) SERCA pump, were investigated and parameters constrained by experimental data to produce the best candidate. Each of the three oscillators generated very good fits with experimental data. However, converting a normal exponential recovery to a transient-decline oscillator predicted that the SERCA pump is the most likely candidate for calreticulin-mediated Ca(2+) release, highlighting the role of this chaperone as a signal protein within the endoplasmic reticulum.