Incidence of ocular manifestations in patients with graft versus host disease after allogeneic stem cell transplant in Riyadh, Saudi Arabia.

AIM: To evaluate the incidence and severity of ocular graft versus host disease (oGVHD) in patients who underwent allogeneic stem cell transplant (SCT) in King Abdul-Aziz Medical City, Saudi Arabia. METHODS: This is a retrospective cohort study conducted in King Abdul Aziz Medical City on patients who underwent allogeneic hematopoietic cell transplant (allo-HCT) from 2010 to 2017. The ocular examination findings including visual acuity, meibomian gland dysfunction, corneal and conjunctival staining with severity, corneal scarring, tear film meniscus and breakup time, anterior and posterior segment examination findings, intraocular pressure, treatment given, punctual plugs used or not, and follow up response were collected. RESULTS: The five years cumulative incidence of oGVHD among post-transplant patients was 56.98% (95%CI 38.6%-71.7%). The potential risk factors assessed for developing ocular manifestation were age, gender, donor's age, donor gender mismatch CD3 and CD34 infusion, while none of the correlates were identified as statistically significant risk factors of developing ocular manifestation. However, the incidence was statistically significantly different between patients diagnosed with acute myelocytic leukemia and acute lymphocytic leukemia (P=0.038). The mean latent period to develop ocular symptoms was 20.5mo. All patients had variable degree of dry eyes. None of the patients developed any posterior segment complication. CONCLUSION: The incidence of oGVHD is low in King Abdul-Aziz Medical City. This can be attributed to the preconditioning and immunosuppressive regime.

Characteristics of clinical trials associated with early results reporting at ClinicalTrials.gov.

OBJECTIVE: We aimed to investigate the trial characteristics associated with earlier results reporting on ClinicalTrials.gov. STUDY DESIGN AND SETTING: We sampled interventional trials registered with ClinicalTrials.gov and examined the time from trial completion to results reporting on ClinicalTrials.gov as the event of interest. A Cox proportional hazards model was used to examine associations between the time to results reporting on ClinicalTrials.gov with funding type, intervention type, number of enrolled participants, trial phase, trial allocation status, and the year of trial completion. The model accounts for multiple risk factors simultaneously. RESULTS: Among 102,404 completed trials, the median follow-up for the result reporting event was 18.5 months (IQR 12.7-33.6), during which time 25% (26,608 of 102,404) had results available on ClinicalTrials.gov. Compared to industry funded trials (18.1 months), non-industry trials (median 18.8 months) had results reported slower (HR 0.35, 95% CI 0.34-0.36); compared to drug trials (18.4 months) non-drug trials (19.0 months) were reported slower (HR 0.61, 95% CI 0.59-0.64); compared to trials with more than 50 participants (18.0 months), smaller trials (19.3 months) were reported slower (HR 0.97, 95% CI 0.94-0.99). CONCLUSION: Non-industry, non-drug, and earlier phase trials reported results on ClinicalTrials.gov more slowly if at all. Much of the efforts aimed at improving trial reporting through structured reporting on ClinicalTrials.gov have been focused on industry funded drug trials, but these results suggest that incentives and tools targeting non-industry and non-drug trials are also needed.

A low-temperature solution-processed indium incorporated zinc oxide electron transport layer for high-efficiency lead sulfide colloidal quantum dot solar cells.

Colloidal quantum dot solar cells (CQDSCs) have achieved remarkable progress recently in terms of mainly surface passivation and composition-matching matrices on CQDs, while improving the overall photoelectric conversion efficiency (PCE) through electron transport layer (ETL) modifications is less explored. We report a low-temperature solution route to synthesize donor (Al3+/Ga3+/In3+) incorporated zinc oxide (AZO/GZO/IZO) ETL films for PbS CQDSCs. Spectroscopic characterization studies indicate that the IZO ETL fabricated with 150 °C annealing can increase the bandgap the most from 3.56 eV to 3.74 eV, possesses enhanced light transmission (∼94%) and finer particle sizes, and importantly shows the most suitable band alignment and charge transfer ability. Well-dispersed PbS CQDs of around 3 nm are synthesized by a N2-protected reflux method and are surface exchanged with 1-ethyl-3-methylimidazolium iodide (EMII) to allow I- grafting and ethanedithiol (EDT) for the active layer and hole transport layer, respectively. The IZO based PbS CQDSC, with a device architecture of ITO/IZO/PbS-EMII/PbS-EDT/Au, shows an enhanced PCE of 11.1% (comparatively 18% higher than that of the ZnO ETL), a VOC value of 0.64 V, and a JSC of 25.8 mA cm-2. The improved performances benefit from the higher recombination resistance and constrained photoluminescence emission with the utilization of the IZO ETL that provides a superior charge transfer property.

The mental health issues of eunuchs in the context of social exclusion.

OBJECTIVE: To study the mental health problems in eunuchs, the neglected segment that has been facing social exclusion and exploitation on behalf of social layers of the society. METHODS: The study was conducted from Jan 2017 to April 2017and adopted a qualitative approach by engaging eight eunuchs' group purposefully through focussed group discussion to unearth the issues related to eunuchs in Hazara Division. The participants were informed in detail, about the purpose of the study and their consent was conferred. The discussion was recorded in local language and their views were transcribed and analysed by comparative statements for drawing results through coding of the target groups. RESULTS: The severe kind of economic and social pressures of poverty and social neglect resulting in depression, anxiety and suicidal tendencies were found among this group, which affected the overall mental health. This showed that, eunuchs have not been provided with basic social rights and can be classed as a neglected gender group. In addition, there is no love and care provided by the kin and relatives which results in the eunuchs facing psychological complications in daily life. CONCLUSIONS: Eunuchs face psychological complications in daily life. The condition necessitates encouragement and social acceptance of eunuch to lead a normal and healthy life in the society. Furthermore socio-psychosocial aid and regular counselling is mandatory for creating hope necessary for leading a normal life.

A rule-based approach for automatically extracting data from systematic reviews and their updates to model the risk of conclusion change.

Few data-driven approaches are available to estimate the risk of conclusion change in systematic review updates. We developed a rule-based approach to automatically extract information from reviews and updates to be used as features for modelling conclusion change risk. Rules were developed to extract relevant information from published Cochrane reviews and used to construct four features: the number of included trials and participants in the reviews, a measure based on the number of participants, and the time elapsed between the search dates. We compared the performance of random forest, decision tree, and logistic regression to predict the conclusion change risk. The performance was measured by accuracy, precision, recall, F1 -score, and area under ROC (AU-ROC). One rule was developed to extract the conclusion change information (96% accuracy, 100 reviews), one for the search date (100% accuracy, 100 reviews), one for the number of included clinical trials (100% accuracy, 100 reviews), and 22 for the number of participants (97.3% accuracy, 200 reviews). For unseen reviews, the random forest classifier showed the highest accuracy (80.8%) and AU-ROC (0.80). All classifiers showed relatively similar performance with overlapping 95% confidence interval (CI). The coverage score was shown to be the most useful feature for predicting the conclusion change risk. Features mined from Cochrane reviews and updates can estimate conclusion change risk. If data from more published reviews and updates were made accessible, data-driven methods to predict the conclusion change risk may be a feasible way to support decisions about updating reviews.

Intravitreal Ranibizumab Injection for the Treatment of Retinopathy of Prematurity.

OBJECTIVES: To evaluate the efficacy of a single injection of 0.3 mg intravitreal ranibizumab for the treatment of retinopathy of prematurity (ROP). METHODS: We conducted this retrospective case series study at King Abdul Aziz Medical City, Riyadh, Saudi Arabia. Seventy-four eyes of 37 preterm infants with ROP stage III with plus disease in zone I, posterior zone II, and aggressive posterior ROP received a single injection of 0.3 mg intravitreal ranibizumab. The favorable outcome measure was complete regression of the disease with normal vascularization of the retina of those infants. RESULTS: The gestational age of the 37 included cases was in the range of 23-28 weeks and their body weight at birth was between 510 and 1,235 g except for one case with 2,550 g under oxygen therapy <7days with severe hypoglycemia. All eyes showed a favorable response in terms of regression of plus disease from the first day after treatment, followed by regression of stage III retinopathy. All patients developed complete vascularization over variable periods of time. CONCLUSION: One injection of 0.3 mg intravitreal ranibizumab is effective in treating ROP stage III mainly in zones I and II.

The risk of conclusion change in systematic review updates can be estimated by learning from a database of published examples.

OBJECTIVES: To determine which systematic review characteristics are needed to estimate the risk of conclusion change in systematic review updates. STUDY DESIGN AND SETTING: We applied classification trees (a machine learning method) to model the risk of conclusion change in systematic review updates, using pairs of systematic reviews and their updates as samples. The classifiers were constructed using a set of features extracted from systematic reviews and the relevant trials added in published updates. Model performance was measured by recall, precision, and area under the receiver operating characteristic curve (AUC). RESULTS: We identified 63 pairs of systematic reviews and updates, of which 20 (32%) exhibited a change in conclusion in their updates. A classifier using information about new trials exhibited the highest performance (AUC: 0.71; recall: 0.75; precision: 0.43) compared to a classifier that used fewer features (AUC: 0.65; recall: 0.75; precision: 0.39). CONCLUSION: When estimating the risk of conclusion change in systematic review updates, information about the sizes of trials that will be added in an update are most useful. Future tools aimed at signaling conclusion change risks would benefit from complementary tools that automate screening of relevant trials.

Trial2rev: Combining machine learning and crowd-sourcing to create a shared space for updating systematic reviews.

OBJECTIVES: Systematic reviews of clinical trials could be updated faster by automatically monitoring relevant trials as they are registered, completed, and reported. Our aim was to provide a public interface to a database of curated links between systematic reviews and trial registrations. MATERIALS AND METHODS: We developed the server-side system components in Python, connected them to a PostgreSQL database, and implemented the web-based user interface using Javascript, HTML, and CSS. All code is available on GitHub under an open source MIT license and registered users can access and download all available data. RESULTS: The trial2rev system is a web-based interface to a database that collates and augments information from multiple sources including bibliographic databases, the ClinicalTrials.gov registry, and the actions of registered users. Users interact with the system by browsing, searching, or adding systematic reviews, verifying links to trials included in the review, and adding or voting on trials that they would expect to include in an update of the systematic review. The system can trigger the actions of software agents that add or vote on included and relevant trials, in response to user interactions or by scheduling updates from external resources. DISCUSSION AND CONCLUSION: We designed a publicly-accessible resource to help systematic reviewers make decisions about systematic review updates. Where previous approaches have sought to reactively filter published reports of trials for inclusion in systematic reviews, our approach is to proactively monitor for relevant trials as they are registered and completed.

Software engineering principles address current problems in the systematic review ecosystem.

Systematic reviewers are simultaneously unable to produce systematic reviews fast enough to keep up with the availability of new trial evidence while overproducing systematic reviews that are unlikely to change practice because they are redundant or biased. Although the transparency and completeness of trial reporting has improved with changes in policy and new technologies, systematic reviews have not yet benefited from the same level of effort. We found that new methods and tools used to automate aspects of systematic review processes have focused on improving the efficiency of individual systematic reviews rather than the efficiency of the entire ecosystem of systematic review production. We use software engineering principles to review challenges and opportunities for improving the interoperability, integrity, efficiency, and maintainability. We conclude by recommending ways to improve access to structured systematic review results. Major opportunities for improving systematic reviews will come from new tools and changes in policy focused on doing the right systematic reviews rather than just doing more of them faster.

Time-to-update of systematic reviews relative to the availability of new evidence.

BACKGROUND: A number of methods for deciding when a systematic review should be updated have been proposed, yet little is known about whether systematic reviews are updated more quickly when new evidence becomes available. Our aim was to examine the timing of systematic review updates relative to the availability of new evidence. METHODS: We performed a retrospective analysis of the update timing of systematic reviews published in the Cochrane Database of Systematic Reviews in 2010 relative to the availability of new trial evidence. We compared the update timing of systematic reviews with and without signals defined by the completion or publication of studies that were included in the updates. RESULTS: We found 43% (293/682) systematic reviews were updated before June 2017, of which 204 included an updated primary outcome meta-analysis (median update time 35.4 months; IQR 25.5-54.0), 38% (77/204) added new trials, and 4% (8/204) reported a change in conclusion. In the 171 systematic reviews with reconcilable trial reporting information, we did not find a clear difference in update timing (p = 0.05) between the 15 systematic reviews with a publication signal (median 25.3 months; IQR 15.3-43.5) and the 156 systematic reviews without a publication signal (median 34.4 months; IQR 25.1-52.2). In the 145 systematic reviews with reconcilable trial completion information, we did not find a difference in update timing (p = 0.33) between the 15 systematic reviews with a trial completion signal (median 26.0 months; IQR 19.3-49.5) and the 130 systematic reviews without a trial completion signal (median 32.4 months; IQR 24.1 to 46.0). CONCLUSION: A minority of 2010 Cochrane reviews were updated before June 2017 to incorporate evidence from new primary studies, and very few updates led to a change in conclusion. We did not find clear evidence that updates were undertaken faster when new evidence was made available. New approaches for finding early signals that a systematic review conclusion is at risk of change may be useful in allocated resources to the updating of systematic reviews.

Conversational agents in healthcare: a systematic review.

Objective: Our objective was to review the characteristics, current applications, and evaluation measures of conversational agents with unconstrained natural language input capabilities used for health-related purposes. Methods: We searched PubMed, Embase, CINAHL, PsycInfo, and ACM Digital using a predefined search strategy. Studies were included if they focused on consumers or healthcare professionals; involved a conversational agent using any unconstrained natural language input; and reported evaluation measures resulting from user interaction with the system. Studies were screened by independent reviewers and Cohen's kappa measured inter-coder agreement. Results: The database search retrieved 1513 citations; 17 articles (14 different conversational agents) met the inclusion criteria. Dialogue management strategies were mostly finite-state and frame-based (6 and 7 conversational agents, respectively); agent-based strategies were present in one type of system. Two studies were randomized controlled trials (RCTs), 1 was cross-sectional, and the remaining were quasi-experimental. Half of the conversational agents supported consumers with health tasks such as self-care. The only RCT evaluating the efficacy of a conversational agent found a significant effect in reducing depression symptoms (effect size d = 0.44, p = .04). Patient safety was rarely evaluated in the included studies. Conclusions: The use of conversational agents with unconstrained natural language input capabilities for health-related purposes is an emerging field of research, where the few published studies were mainly quasi-experimental, and rarely evaluated efficacy or safety. Future studies would benefit from more robust experimental designs and standardized reporting. Protocol Registration: The protocol for this systematic review is registered at PROSPERO with the number CRD42017065917.

A shared latent space matrix factorisation method for recommending new trial evidence for systematic review updates.

BACKGROUND: Clinical trial registries can be used to monitor the production of trial evidence and signal when systematic reviews become out of date. However, this use has been limited to date due to the extensive manual review required to search for and screen relevant trial registrations. Our aim was to evaluate a new method that could partially automate the identification of trial registrations that may be relevant for systematic review updates. MATERIALS AND METHODS: We identified 179 systematic reviews of drug interventions for type 2 diabetes, which included 537 clinical trials that had registrations in ClinicalTrials.gov. Text from the trial registrations were used as features directly, or transformed using Latent Dirichlet Allocation (LDA) or Principal Component Analysis (PCA). We tested a novel matrix factorisation approach that uses a shared latent space to learn how to rank relevant trial registrations for each systematic review, comparing the performance to document similarity to rank relevant trial registrations. The two approaches were tested on a holdout set of the newest trials from the set of type 2 diabetes systematic reviews and an unseen set of 141 clinical trial registrations from 17 updated systematic reviews published in the Cochrane Database of Systematic Reviews. The performance was measured by the number of relevant registrations found after examining 100 candidates (recall@100) and the median rank of relevant registrations in the ranked candidate lists. RESULTS: The matrix factorisation approach outperformed the document similarity approach with a median rank of 59 (of 128,392 candidate registrations in ClinicalTrials.gov) and recall@100 of 60.9% using LDA feature representation, compared to a median rank of 138 and recall@100 of 42.8% in the document similarity baseline. In the second set of systematic reviews and their updates, the highest performing approach used document similarity and gave a median rank of 67 (recall@100 of 62.9%). CONCLUSIONS: A shared latent space matrix factorisation method was useful for ranking trial registrations to reduce the manual workload associated with finding relevant trials for systematic review updates. The results suggest that the approach could be used as part of a semi-automated pipeline for monitoring potentially new evidence for inclusion in a review update.

A systematic review of the processes used to link clinical trial registrations to their published results.

BACKGROUND: Studies measuring the completeness and consistency of trial registration and reporting rely on linking registries with bibliographic databases. In this systematic review, we quantified the processes used to identify these links. METHODS: PubMed and Embase databases were searched from inception to May 2016 for studies linking trial registries with bibliographic databases. The processes used to establish these links were categorised as automatic when the registration identifier was available in the bibliographic database or publication, or manual when linkage required inference or contacting of trial investigators. The number of links identified by each process was extracted where available. Linear regression was used to determine whether the proportions of links available via automatic processes had increased over time. RESULTS: In 43 studies that examined cohorts of registry entries, 24 used automatic and manual processes to find articles; 3 only automatic; and 11 only manual (5 did not specify). Twelve studies reported results for both manual and automatic processes and showed that a median of 23% (range from 13 to 42%) included automatic links to articles, while 17% (range from 5 to 42%) of registry entries required manual processes to find articles. There was no evidence that the proportion of registry entries with automatic links had increased (R 2 = 0.02, p = 0.36). In 39 studies that examined cohorts of articles, 21 used automatic and manual processes; 9 only automatic; and 2 only manual (7 did not specify). Sixteen studies reported numbers for automatic and manual processes and indicated that a median of 49% (range from 8 to 97%) of articles had automatic links to registry entries, and 10% (range from 0 to 28%) required manual processes to find registry entries. There was no evidence that the proportion of articles with automatic links to registry entries had increased (R 2 = 0.01, p = 0.73). CONCLUSIONS: The linkage of trial registries to their corresponding publications continues to require extensive manual processes. We did not find that the use of automatic linkage has increased over time. Further investigation is needed to inform approaches that will ensure publications are properly linked to trial registrations, thus enabling efficient monitoring of trial reporting.

Systematic review protocol assessing the processes for linking clinical trial registries and their published results.

INTRODUCTION: Clinical trial registries are an important source of information for tracking clinical trials from their inception through to their reporting, and have been used to measure publication bias and outcome reporting bias. Our aim is to survey and quantify the processes that have been used to identify links between clinical trial registries and published trial reports in studies that rely on these links to evaluate the completeness and accuracy of trial reporting. METHODS AND ANALYSIS: We will identify studies that describe a process for identifying the links between a trial registry included in the WHO International Clinical Trial Registry Platform and published trial results, and use those links to evaluate the completeness and accuracy of trial reporting. Information extracted from the studies will include the purpose and application domain of the study, registries used or searched, processes by which the links were identified, the study period and proportions for which links were found. We will summarise what is known about the number and availability of links between clinical trial registries and published results, and examine how automatic linking, inference and inquiry processes have been used to identify links since the introduction of trial registries. ETHICS AND DISSEMINATION: The systematic review is focused on the analysis of secondary data and does not require ethics approval. The results of the systematic review will be used to inform standard processes used to identify links to and from clinical trial registries in studies that evaluate the completeness and accuracy of clinical trial reports, as well as systematic reviews. Our findings will be disseminated by publishing the systematic review in a peer-reviewed journal, and by engaging with stakeholders from clinical trial registries and bibliographic databases.

The development of BAC-end sequence-based microsatellite markers and placement in the physical and genetic maps of soybean.

The composite map of soybean shared among Soybase, LIS and SoyGD (March 2006) contained 3,073 DNA markers in the "Locus" class. Among the markers were 1,019 class I microsatellite markers with 2-3 bp simple sequence repeats (SSRs) of >10 iterations (BARC-SSR markers). However, there were few class II SSRs (2-5 bp repeats with <10 iterations; mostly SIUC-Satt markers). The aims here were to increase the number of classes I and II SSR markers and to integrate bacterial artificial chromosome (BAC) clones onto the soybean physical map using the markers. Used was 10 Mb of BAC-end sequence (BES) derived from 13,473 reads from 7,050 clones constituting minimum tile path 2 of the soybean physical map ( http://www.soybeangenome.siu.edu ; SoyGD). Identified were 1,053 1-6 bp motif, repeat sequences, 333 from class I (>10 repeats) and 720 from class II (<10 repeats). Potential markers were shown on the MTP_SSR track at Gbrowse. Primers were designed as 20-24 bp oligomers that had Tm of 55 +/- 1 C that would generate 100-500 bp amplicons. About 853 useful primer pairs were established. Motifs were not randomly distributed with biases toward AT rich motifs. Strong biases against the GC motif and all tetra-nucleotide repeats were found. The markers discovered were useful. Among the first 135 targeted for use in genetic map improvement about 60% of class II markers and 75% of class I markers were polymorphic among on the parents of four recombinant inbred line (RIL) populations. Many of the BES-based SSRs were located on the soybean genetic map in regions with few BARC-SSR markers. Therefore, BES-based SSRs represent useful tools for genetic map development in soybean. New members of a consortium to map the markers in additional populations are invited.

The Soybean Genome Database (SoyGD): a browser for display of duplicated, polyploid, regions and sequence tagged sites on the integrated physical and genetic maps of Glycine max.

Genomes that have been highly conserved following increases in ploidy (by duplication or hybridization) like Glycine max (soybean) present challenges during genome analysis. At http://soybeangenome.siu.edu the Soybean Genome Database (SoyGD) genome browser has, since 2002, integrated and served the publicly available soybean physical map, bacterial artificial chromosome (BAC) fingerprint database and genetic map associated genomic data. The browser shows both build 3 and build 4 contiguous sets of clones (contigs) of the soybean physical map. Build 4 consisted of 2854 contigs that encompassed 1.05 Gb and 404 high-quality DNA markers that anchored 742 contigs. Many DNA markers anchored sets of 2-8 different contigs. Each contig in the set represented a homologous region of related sequences. GBrowse was adapted to show sets of homologous contigs at all potential anchor points, spread laterally and prevented from overlapping. About 8064 minimum tiling path (MTP2) clones provided 13,473 BAC end sequences (BES) to decorate the physical map. Analyses of BES placed 2111 gene models, 40 marker anchors and 1053 new microsatellite markers on the map. Estimated sequence tag probes from 201 low-copy gene families located 613 paralogs. The genome browser portal showed each data type as a separate track. Tetraploid, octoploid, diploid and homologous regions are shown clearly in relation to an integrated genetic and physical map.