Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Blindness and visual impairment due to age-related cataract in sub-Saharan Africa: a systematic review of recent population-based studies.

AIM: We aimed to evaluate age-related cataract as a contributor to blindness and visual impairment (VI) in sub-Saharan Africa (SSA). METHODS: A systematic review of population-based studies published between 2000 and October 2012. Prevalence and proportions of blindness and VI due to cataract, cataract surgical coverage (CSC), per cent intraocular lens (IOL) implantation and visual outcomes of surgery in accordance with WHO criteria were ascertained. RESULTS: Data from 17 surveys (subjects mostly aged ≥ 50-years-old) from 15 different countries in SSA were included, comprising 96 402 people. Prevalence of blindness (presenting visual acuity <3/60 in better eye) ranged from 0.1% in Uganda to 9.0% in Eritrea, and the proportion of total blindness due to cataract ranged between 21% and 67%. Cataract was the principal cause of blindness and VI in 15 and 14 studies, respectively. There was a strong positive correlation between good visual outcomes and IOL use (R=0.69, p=0.027). Considerable inter-study heterogeneity was evident in CSC and visual outcomes following surgery, and between 40% and 100% of operations had used IOL. CONCLUSIONS: Cataract represents the principal cause of blindness and VI and should remain a priority objective for eye care in SSA. However, the prevalence of blindness and VI due to cataract was variable and may reflect differences in the availability of cataract surgical programmes and cataract incidence

Functional presbyopia in a rural Kenyan population: the unmet presbyopic need.

BACKGROUND: Presbyopia is the most common reason for requiring spectacles in low-income regions, although the unmet need for presbyopic spectacles in these regions is very high. The aim of this study was to estimate the prevalence of presbyopia, and the functional impairment and spectacle use among persons with presbyopia in a rural Kenyan population. METHODS: A cross-sectional study was carried out in the Rift Valley, Kenya. Clusters were selected through probability-proportionate to size sampling, and people aged >/=50 years within the clusters were identified through compact segment sampling. Within the context of this survey, 130 eligible participants were selected for interview and underwent near-vision testing. Functional presbyopia was defined as requiring at least +1.00 dioptre in order to read the N8 optotype at a distance of 40 cm in the participant's usual visual state. Participants were corrected to the nearest 0.25 dioptre in order to see N8. Unmet and met presbyopic need, and presbyopic correction coverage were calculated. RESULTS: Functional presbyopia was found in 111 participants (85.4%). Mean age was lower in those with presbyopia (64.1 years vs. 71.5 years, P = 0.004). Increasing degree of addition required to see N8 was significantly associated with increased difficulty with reading (P = 0.04), sewing (P = 0.03), recognizing small objects (P = 0.02) and harvesting grains (P = 0.05). Among participants with functional presbyopia, 5.4% wore reading glasses and 25.2% had prior contact with an eye care professional. The unmet presbyopic need was 80.0%, met presbyopic need was 5.4% and presbyopic correction coverage was 6.3%. Cost was cited as the main barrier to spectacle use in 62% of participants with presbyopia. CONCLUSION: In low-income regions, there is a high prevalence of uncorrected presbyopia, which is associated with near-vision functional impairment. Provision of spectacles for near vision remains a priority in low-income regions

Follow-up survey of cataract surgical coverage and barriers to cataract surgery at Nkhoma, Malawi.

PURPOSE: Nkhoma Eye Hospital, Malawi provides high volume, high quality free cataract surgery to people in its catchment region of Central-Malawi. However, a previous survey in 2000 indicated that only 1 in 7 people with bilateral blindness from cataract had received surgery in a 10-mile radius of Nkhoma. METHODS: We conducted a population-based survey in 2006 in the 32 villages within a 10-mile radius of Nkhoma Hospital in people aged ≥ 40 years in order to investigate the cataract surgical coverage (CSC) and barriers to cataract surgery. RESULTS: The prevalence of blindness (visual acuity [VA] <3/60 in better eye) in 835 people aged ≥ 40 was 1.3% (95% CI 0.5-2.1), of which 36.4% was due to cataract. Overall, the CSC was 83.3%, and for eyes (VA<3/60) was 66.0%. The CSC was lower in females compared to males (73.3% vs. 100.0%. P < 0.001). The most common barrier to surgery was cost (58%). CONCLUSION: Our results demonstrate a 5-fold increase in coverage in the 6 years, primarily by increasing efficiency of the service provider and providing a community screening and referral service. Supporting the ophthalmic personnel with appropriate infrastructure and management has been central to this shift. Implementing an active case finding and referral mechanism has enabled this unit to provide regular high volume cataract surgery. There is a need to understand the factors influencing perceptions about cost as a barrier in this community and the disparity between need and access to services for women