Although including public contributors as members of research teams is becoming common, there are few reflections on how they have been incorporated, and almost none of these reflections are ...co-produced with public contributors. This commentary, written by both academics and a public contributor, reflects on Patient and Public Involvement (PPI) activities when undertaking a framework analysis of PPI sections of annual reports from the National Institute for Health and care Research (NIHR) funded research centres. The UK Standards for Public Involvement (inclusive opportunities, working together, support and learning, communications, impact and governance) were used to structure our reflections. Key topics of reflection were: how difficult it is, in practice, to incorporate PPI into all aspects of the research cycle, especially when completing a commissioned research project on a short time-frame, and the complexities of incorporating PPI into qualitative analysis. Although useful when reflecting upon our own PPI practices, ways in which the UK Standards for Public Involvement could be improved were suggested. We hope that the co-produced recommendations can be used by other teams engaging with public contributors.
Within the United Kingdom (UK), the National Institute for Health and Care Research is the largest funder of health and social care research, and additionally funds research centres that support the ...development and delivery of research. Each year, award-holders of these research centres are required to write a report about their activities, including a summary of Patient and Public Involvement and Engagement (PPIE) activities. This study aimed to evaluate the PPIE sections of annual reports to identify best practice and challenges; this could inform future delivery of PPIE activities. A framework documentary analysis informed by the six UK Standards for Public Involvement ('Inclusive opportunities', 'Working together', 'Support and learning', 'Communications', 'Impact' and 'Governance') was conducted on 112 reports. A quality improvement framework ('Insights') was used to evaluate quality as one of: 'Welcoming', 'Listening', 'Learning' and 'Leading'. Recommendations from this review were co-developed with stakeholders and public contributors. Reports documented varying levels of quality in PPIE activities which spanned across all six UK Standards. Award-holders either intended to, or were actively working towards, increasing access and inclusivity of public involvement opportunities. Methods of working with public contributors were varied, including virtual and in-person meetings. Most award-holders offered PPIE support and learning opportunities for both public contributors and staff. Some award-holders invited public contributors to co-produce communication plans relating to study materials and research findings. The impact of public involvement was described in terms of benefits to public contributors themselves, and on an organisation and project level. Many award-holders reported inviting public contributors to share decision-making within and about governance structures. This evaluation identified that most annual reports contained evidence of good quality PPIE practice with learning from public contributors. Using the UK Standards and Insights framework enabled exploration of the breadth and quality of PPIE activities. Recommendations include the need for a platform for centres to access and share PPIE best practice and for centres to collaborate with local and national partners to build relationships with the public through inclusive community engagement.
Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative ...contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error.
We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals UIs) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older.
Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change −0·2% 95% UI −1·5 to 1·0; 2019 prevalence 9·58 cases per 1000 people 95% IU 8·51 to 10·8, 2010 prevalence 96·0 cases per 1000 people 86·0 to 107·0). Age-standardised prevalence of avoidable blindness decreased by −15·4% –16·8 to −14·3, while avoidable MSVI showed no change (0·5% –0·8 to 1·6). However, the number of cases increased for both avoidable blindness (10·8% 8·9 to 12·4) and MSVI (31·5% 30·0 to 33·1). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases 9% IU 12·7–18·0), followed by glaucoma (3·6 million cases 2·8–4·4), undercorrected refractive error (2·3 million cases 1·8–2·8), age-related macular degeneration (1·8 million cases 1·3–2·4), and diabetic retinopathy (0·86 million cases 0·59–1·23). Leading causes of MSVI were undercorrected refractive error (86·1 million cases 74·2–101·0) and cataract (78·8 million cases 67·2–91·4).
Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached.
Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.
Much remains unknown about the population history of early modern humans in southeast Asia, where the archaeological record is sparse and the tropical climate is inimical to the preservation of ...ancient human DNA
. So far, only two low-coverage pre-Neolithic human genomes have been sequenced from this region. Both are from mainland Hòabìnhian hunter-gatherer sites: Pha Faen in Laos, dated to 7939-7751 calibrated years before present (yr cal BP; present taken as AD 1950), and Gua Cha in Malaysia (4.4-4.2 kyr cal BP)
. Here we report, to our knowledge, the first ancient human genome from Wallacea, the oceanic island zone between the Sunda Shelf (comprising mainland southeast Asia and the continental islands of western Indonesia) and Pleistocene Sahul (Australia-New Guinea). We extracted DNA from the petrous bone of a young female hunter-gatherer buried 7.3-7.2 kyr cal BP at the limestone cave of Leang Panninge
in South Sulawesi, Indonesia. Genetic analyses show that this pre-Neolithic forager, who is associated with the 'Toalean' technocomplex
, shares most genetic drift and morphological similarities with present-day Papuan and Indigenous Australian groups, yet represents a previously unknown divergent human lineage that branched off around the time of the split between these populations approximately 37,000 years ago
. We also describe Denisovan and deep Asian-related ancestries in the Leang Panninge genome, and infer their large-scale displacement from the region today.
Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the ...CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials.
Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels.
We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival.
First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
•Sotorasib showed promising efficacy in heavily pretreated real-world patients.•ECOG, brain metastases, STK11- and TP53-mutations had no impact on the ORR.•Patients with a co-occurring KEAP1-mutation derive less benefit.•Sotorasib may have initial intracranial activity, albeit only for a short time.
To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of ...global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990–2020, and forecasts for 2050.
We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals UIs) of mild vision impairment (presenting visual acuity ≥6/18 and <6/12), moderate and severe vision impairment (<6/18 to 3/60), and blindness (<3/60 or less than 10° visual field around central fixation); and vision impairment from uncorrected presbyopia (presenting near vision <N6 or <N8 at 40 cm where best-corrected distance visual acuity is ≥6/12). We forecast estimates of vision loss up to 2050.
In 2020, an estimated 43·3 million (95% UI 37·6–48·4) people were blind, of whom 23·9 million (55%; 20·8–26·8) were estimated to be female. We estimated 295 million (267–325) people to have moderate and severe vision impairment, of whom 163 million (55%; 147–179) were female; 258 million (233–285) to have mild vision impairment, of whom 142 million (55%; 128–157) were female; and 510 million (371–667) to have visual impairment from uncorrected presbyopia, of whom 280 million (55%; 205–365) were female. Globally, between 1990 and 2020, among adults aged 50 years or older, age-standardised prevalence of blindness decreased by 28·5% (–29·4 to −27·7) and prevalence of mild vision impairment decreased slightly (–0·3%, −0·8 to −0·2), whereas prevalence of moderate and severe vision impairment increased slightly (2·5%, 1·9 to 3·2; insufficient data were available to calculate this statistic for vision impairment from uncorrected presbyopia). In this period, the number of people who were blind increased by 50·6% (47·8 to 53·4) and the number with moderate and severe vision impairment increased by 91·7% (87·6 to 95·8). By 2050, we predict 61·0 million (52·9 to 69·3) people will be blind, 474 million (428 to 518) will have moderate and severe vision impairment, 360 million (322 to 400) will have mild vision impairment, and 866 million (629 to 1150) will have uncorrected presbyopia.
Age-adjusted prevalence of blindness has reduced over the past three decades, yet due to population growth, progress is not keeping pace with needs. We face enormous challenges in avoiding vision impairment as the global population grows and ages.
Brien Holden Vision Institute, Fondation Thea, Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.
Comprehensive tobacco control policies are lacking in Indonesia where smoking prevalence in males is among the highest in the world. This study aims to explore the knowledge, attitude, opportunities ...and challenges to tobacco control among local stakeholders.
This is a qualitative study using in-depth interviews. Four study areas included Bengkulu Province, Bengkulu City, Seluma District, and Kaur District. Eighteen participants interviewed were from policymakers, legislators, and civil societies during November-December 2020. Thematic data analysis was used.
While knowledge and support of the existing Smoke Free Policy (SFP) were high, that of other policies such as outdoor tobacco advertising (OTA) ban and tobacco product display ban were low. Among others, one opportunity was there is already SFP regulation in each study area, to which such bans can be added. Among others, three major challenges were: (a) lack of enforcement of the existing SFP, (b) lack of national regulation to ban OTA and product display, and (c) counter actions by the tobacco industry.
The opportunities and challenges identified could be lessons learnt for more comprehensive tobacco control especially by local governments in Indonesia and other countries with similar settings.
Renewable energy technology is a topic that has often been raised in many studies lately. To support the 2020-2024 PRN (National Research Priority) program in the Maritime sector, the Researcher has ...developed FOWT (Floating Offshore Wind Turbine), a Classic SPAR design to operate and serve the eastern Indonesia region. A novelty design, namely the “Motion Reduction Device” (MRD), is installed at the bottom of the FOWT floater intended to increase its natural period and reduce heaving and pitching motion when exposed to environmental loads. The ANSYS FLUENT Computational Fluid Dynamics (CFD) simulation of heave decay is applied to calculate natural periods for several MRD types. A mesh convergence study was carried out to determine the best mesh size. The damping terms are derived by matching the heave motion obtained using the equation of motion by changing the damping time with linear, quadratic, or a combination of linear and quadratic. The added mass and damping results are then plotted in a graph and table. It has been demonstrated that MRD has a more significant impact than simply installing a heave plate at the bottom of the FOWT by significantly increasing added mass and damping.
The human microbiota (the microscopic organisms that inhabit us) and microbiome (their genes) hold considerable potential for improving pharmacological practice. Recent advances in multi-"omics" ...techniques have dramatically improved our understanding of the constituents of the microbiome and their functions. The implications of this research for human health, including microbiome links to obesity, drug metabolism, neurological diseases, cancer, and many other health conditions, have sparked considerable interest in exploiting the microbiome for targeted therapeutics. Links between microbial pathways and disease states further highlight a rich potential for companion diagnostics and precision medicine approaches. For example, the success of fecal microbiota transplantation to treat Clostridium difficile infection has already started to redefine standard of care with a microbiome-directed therapy. In this review we briefly discuss the nature of human microbial ecosystems and with pathologies and biological processes linked to the microbiome. We then review emerging computational metagenomic, metabolomic, and wet lab techniques researchers are using today to learn about the roles host-microbial interactions have with respect to pharmacological purposes and vice versa. Finally, we describe how drugs affect the microbiome, how the microbiome can impact drug response in different people, and the potential of the microbiome itself as a source of new therapeutics.
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