Hydroxychloroquine/Chloroquine for the Treatment of Hospitalized Patients with COVID-19: An Individual Participant Data Meta-Analysis

Importance: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data (IPD), including unanalyzed data from trials terminated early, enables further investigation of the efficacy and safety of HCQ/CQ. Objective: To assess efficacy of HCQ/CQ in patients hospitalized with COVID-19, both overall and in prespecified subgroups. Data Sources: ClinicalTrials.gov was searched multiple times in May-June 2020. Principal investigators of US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients were invited to collaborate in this IPD meta-analysis. Study Selection: RCTs in which: (1) HCQ/CQ was a treatment arm; (2) patient informed consent and/or individual study IRB approval allowed for data sharing; (3) principal investigators/their institutions signed a data use agreement for the present study; and (4) the outcomes defined in this study were recorded or could be extrapolated. Data Extraction and Synthesis: Wherever possible, harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator, then shared via a secure online data sharing platform to create a pooled data set. When this was not possible, individual study data were harmonized and merged manually. Data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Main Outcome(s) and Measure(s): 7-point ordinal scale, measured between day 28 and 35 post-enrollment. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We found no evidence of a difference in ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions and Relevance: The findings of this IPD meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

High Flow Nasal Oxygen versus Conventional Oxygen Therapy in Gastrointestinal Endoscopy with Conscious Sedation: A Systematic Review and Meta-Analysis

Review question / Objective: To compare the efficacy of high flow nasal oxygen with conventional oxygen therapy to prevent hypoxemia in gastrointestinal endoscopy with conscious sedation. Condition being studied: High flow nasal oxygen, a novel technique, may be an alternative to conventional oxygen therapy. High flow nasal oxygen can deliver heated and humidified oxygen via special nasal cannula with high flow (up to 70 L/min). It has been applied to improve oxygenation in clinical entities, favored by increasing evidence supporting its efficacy. Recently, the use of high flow nasal oxygen has spreaded to gastrointestinal endoscopy. However, the efficacy of high flow nasal oxygen in gastrointestinal endoscopy has not yet been well evaluated due to small sample size of the individual study and conflicting results.

The Hierarchization of Product Attributes

This study aims to investigate which hotels' attributes are most valued by the guests of the main markets of Porto. The guests' knowledge, preferences, and needs are crucial data that impact customer satisfaction. As a people-to-people industry, the hotel industry must consider the heterogeneity of its markets and invest in improving its services, considering the aspects they value. However, is the heterogeneity pronounced that much? Or are there any similarities between markets? Guests do not have similar satisfaction levels, so to guarantee the best experience for the most significant number of customers, these should be studied by market segments, once individual study would be impracticable. Through the comments made on the Booking.com, following the assumption that guests comment on what they value, the attributes that guests of different nationalities refer to Porto hotels have been collected. From the analysis of all the collected data, it can be concluded that all the main markets' value attributes and the fundamental differences are based on the hierarchy of these attributes.

Meta-Analysis of Standard Temozolomide versus Extended Adjuvant Temozolomide following concurrent Radiochemotherapy in newly-diagnosed Glioblastoma (MASTER-G)

Review question / Objective: To assess the safety and efficacy of extended adjuvant temozolomide compared to standard adjuvant temozolomide after concurrent radiochemotherapy in patients with newly-diagnosed glioblastoma. Condition being studied: Newly-diagnosed glioblastoma. Eligibility criteria: Prospective clinical trials randomly assigning patients to extended (>6-cycles) adjuvant TMZ (experimental arm) or standard (6-cycles) adjuvant TMZ will be included. Randomization in an individual study may have been done upfront before concurrent phase (RT/TMZ), after completion of concurrent RT/TMZ and before starting adjuvant phase, or after completion of standard adjuvant TMZ (6-cycles). Emulated RCTs, quasi-randomized trials, propensity matched analyses, non-randomized comparative studies, or observational studies will not be considered in this review.

Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays

Tissue microarrays (TMAs) have been used in thousands of cancer biomarker studies. To what extent batch effects, measurement error in biomarker levels between slides, affects TMA-based studies has not been assessed systematically. We evaluated 20 protein biomarkers on 14 TMAs with prospectively collected tumor tissue from 1,448 primary prostate cancers. In half of the biomarkers, more than 10% of biomarker variance was attributable to between-TMA differences (range, 1-48%). We implemented different methods to mitigate batch effects (R package batchtma), tested in plasmode simulation. Biomarker levels were more similar between mitigation approaches compared to uncorrected values. For some biomarkers, associations with clinical features changed substantially after addressing batch effects. Batch effects and resulting bias are not an error of an individual study but an inherent feature of TMA-based protein biomarker studies. They always need to be considered during study design and addressed analytically in studies using more than one TMA.

MECP2pedia: A Comprehensive Transcriptome Portal for MECP2 Disease Research

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2s molecular role. Focusing on individual transcriptomic studies yields inconsistent differentially expressed genes. We have aggregated and homogeneously processed modern public MeCP2 transcriptome data, which we present in a web portal. With this big data, we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found distinct consistently up and downregulated subsets within these genes. We observe enrichment for this mouse core in other species MeCP2 models and see overlap between this core and ASD models. Analysis of signal to noise finds that many studies lack enough biological replicates. By integrating and examining transcriptomic data at scale, we have generated a valuable resource and insight on MeCP2 function.

The emergence of chloroquine-sensitive Plasmodium falciparum is influenced by selected communities in some parts of the Central Region of Ghana

Background The return of chloroquine-sensitive Plasmodium falciparum in sub-Saharan Africa countries offers the opportunity for the reintroduction of chloroquine (CQ) either in combination with other drugs or as a single therapy for the management of malaria. This study assesses the influence of individual study sites on the selection of CQ sensitive P. falciparum markers in the Central region of Ghana. Methods Genomic DNA was extracted from an archived filter paper blood blot from Cape Coast, Elmina, Assin Fosu, and Twifo Praso using the Chelex DNA extraction method. The age metadata of the patients from whom the blood spots were taken was collected. The prevalence of CQ-sensitive markers of pfcrt K76 and pfmdr1 N86 was performed using nested PCR and RFLP. The data were analysed using Chi-square and Odd ratio. Results The overall prevalence of CQ-sensitive P. falciparum markers, pfcrt K76 and pfmdr1 N86 in the Central Region of Ghana were 142 out of 184 (77.17%) and 180 out of 184 (97.83%), respectively. The distribution of pfcrt K76 was assessed among the age groups per the individual study sites. 12 out of 33 (36.36%), 8 out of 33 (24.24%) and 6 out of 33 (18.18%) of pfcrt K76 CQ-sensitive marker were isolated from age 0 to 5 years, 16 to 30 years and 31 to 45 years old respectively at Cape Coast. Assin Fosu and Twifo Praso had the highest pfcrt K76 prevalence in 0–5 years, followed by 16–30 years and 6–15 years of age. The results showed that there was a significant prevalence of pfcrt K76 in all study sites; Cape Coast (χ2 = 26.48, p < 0.0001), Assin Fosu (χ2 = 37.67, p < 0.0001), Twifo Praso (χ2 = 32.25, p < 0.0001) and Elmina (χ2 = 17.88, p < 0.0001). Again, the likelihood to detect pfcrt K76 (OR (95% CI) was 7.105 (3.118–17.14), p < 0.0001 and pfmdr1 (2.028 (1.065–3.790), p < 0.001) among P. falciparum isolates from Cape Coast to be seven times and two times, respectively. Conclusion The study showed a significant selection and expansion of chloroquine-sensitive P. falciparum markers in all the selected study areas in the Central region. This finding has a significant implication for the future treatment, management, and control of P. falciparum malaria.

The Impact of IT Developments on Space Usage in Manukau Institute of Technology (MIT) Library

<p>There are numerous claims of whether physical spaces of academic libraries still required as more resources moved from print to electronic. This project set out to investigate the impact of IT developments on space usage in Manukau Institute of Technology (MIT) Library in order to help librarians and space planners to manage the physical spaces better, and improve existing spaces. They will be able to make informed decisions when planning for future use of spaces. A web based questionnaire was used to collect data on who was using the library and the activities in which they are engaged. There were 261 complete responses to the questionnaire. The researcher also conducted interviews with the Associate Librarian and the Institute Librarian from MIT Library on asking them how they have planed and managed the physical spaces in MIT Library. In addition, the researcher also examined the MIT Library statistics: Data in relations to volumes of print serial and monograph acquired, total number of issues, total number of library visits, total reference enquiries from 2003 to 2008 was analysed and then presented in charts, graphs and tables. The majority of respondents from the online questionnaire were found to be undergraduate fulltime students between the age of 20-25, and they were mainly female students. More than half of the respondents reported they can easily find the place to carry out individual study and group work. However, some respondents commented that in certain times of the year (for example, assignments/exams period) it is very difficult to find a place for individual study and/or group work. The majority of the respondents also reported they mainly come to the library to work on their assignments and study for tests/exams. The Institute Librarian and Associate Librarian mentioned that instead of just storing print materials, the physical spaces is also required to house more computers to access online resources, for quiet study space and group study rooms, and to provide more electrical outlets to access wireless using laptops. The conclusion reached was that the physical spaces of MIT Library still remains essential even through more resources has moved from print to electronic.</p>

The Impact of IT Developments on Space Usage in Manukau Institute of Technology (MIT) Library

<p>There are numerous claims of whether physical spaces of academic libraries still required as more resources moved from print to electronic. This project set out to investigate the impact of IT developments on space usage in Manukau Institute of Technology (MIT) Library in order to help librarians and space planners to manage the physical spaces better, and improve existing spaces. They will be able to make informed decisions when planning for future use of spaces. A web based questionnaire was used to collect data on who was using the library and the activities in which they are engaged. There were 261 complete responses to the questionnaire. The researcher also conducted interviews with the Associate Librarian and the Institute Librarian from MIT Library on asking them how they have planed and managed the physical spaces in MIT Library. In addition, the researcher also examined the MIT Library statistics: Data in relations to volumes of print serial and monograph acquired, total number of issues, total number of library visits, total reference enquiries from 2003 to 2008 was analysed and then presented in charts, graphs and tables. The majority of respondents from the online questionnaire were found to be undergraduate fulltime students between the age of 20-25, and they were mainly female students. More than half of the respondents reported they can easily find the place to carry out individual study and group work. However, some respondents commented that in certain times of the year (for example, assignments/exams period) it is very difficult to find a place for individual study and/or group work. The majority of the respondents also reported they mainly come to the library to work on their assignments and study for tests/exams. The Institute Librarian and Associate Librarian mentioned that instead of just storing print materials, the physical spaces is also required to house more computers to access online resources, for quiet study space and group study rooms, and to provide more electrical outlets to access wireless using laptops. The conclusion reached was that the physical spaces of MIT Library still remains essential even through more resources has moved from print to electronic.</p>