bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis
Authors: Stone Marc B , Yaseen Zimri S , Miller Brian J , Richardville Kyle , Kalaria Shamir N , Kirsch Irving 
Published: August 2022

AbstractObjectivesTo characterize individual participant level response distributions to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration from 1979 to 2016.DesignIndividual participant data analysis.Population232 randomized, double blind, placebo controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016, comprising 73 388 adult and child participants meeting the inclusion criteria for efficacy studies on antidepressants.Main outcome measuresResponses were converted to Hamilton Rating Scale for Depression (HAMD17) equivalent scores where other measures were used to assess efficacy. Multivariable analyses examined the effects of age, sex, baseline severity, and year of the study on improvements in depressive symptoms in the antidepressant and placebo groups. Response distributions were analyzed with finite mixture models.ResultsThe random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86). Differences between drug and placebo increased significantly (P<0.001) with greater baseline severity. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were found. The best fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0, 8.9, and 1.7 points. These distributions were designated Large, Non-specific, and Minimal responses, respectively. Participants who were treated with a drug were more likely to have a Large response (24.5%v9.6%) and less likely to have a Minimal response (12.2.%v21.5%).ConclusionsThe trimodal response distributions suggests that about 15% of participants have a substantial antidepressant effect beyond a placebo effect in clinical trials, highlighting the need for predictors of meaningful responses specific to drug treatment.
Risk of covid-19 related deaths for SARS-CoV-2 omicron (B.1.1.529) compared with delta (B.1.617.2): retrospective cohort study
Authors: Ward Isobel L , Bermingham Charlotte , Ayoubkhani Daniel , Gethings Owen J , Pouwels Koen B , Yates Thomas , Khunti Kamlesh , Hippisley-Cox Julia , Banerjee Amitava , Walker Ann Sarah , Nafilyan Vahé 
Published: August 2022

AbstractObjectiveTo assess the risk of covid-19 death after infection with omicron BA.1 compared with delta (B.1.617.2).DesignRetrospective cohort study.SettingEngland, United Kingdom, from 1 December 2021 to 30 December 2021.Participants1 035 149 people aged 18-100 years who tested positive for SARS-CoV-2 under the national surveillance programme and had an infection identified as omicron BA.1 or delta compatible.Main outcome measuresThe main outcome measure was covid-19 death as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause specific Cox proportional hazard regression models (censoring non-covid-19 deaths) were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, index of multiple deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Interactions between variant and sex, age, vaccination status, and comorbidities were also investigated.ResultsThe risk of covid-19 death was 66% lower (95% confidence interval 54% to 75%) for omicron BA.1 compared with delta after adjusting for a wide range of potential confounders. The reduction in the risk of covid-19 death for omicron compared with delta was more pronounced in people aged 18-59 years (number of deaths: delta=46, omicron=11; hazard ratio 0.14, 95% confidence interval 0.07 to 0.27) than in those aged ≥70 years (number of deaths: delta=113, omicron=135; hazard ratio 0.44, 95% confidence interval 0.32 to 0.61, P<0.0001). No evidence of a difference in risk was found between variant and number of comorbidities.ConclusionsThe results support earlier studies showing a reduction in severity of infection with omicron BA.1 compared with delta in terms of hospital admission. This study extends the research to also show a reduction in the risk of covid-19 death for the omicron variant compared with the delta variant.
Effect of thiamine supplementation on glycaemic outcomes in adults with type 2 diabetes: a systematic review and meta-analysis
Authors: Muley Arti , Fernandez Ritin , Green Heidi , Muley Prasad 
Published: August 2022

BackgroundPatients with type 2 diabetes mellitus (T2DM) have been shown to have thiamine deficiency. Dietary supplementation is an economic strategy to control blood glucose. Objective: To evaluate effectiveness of thiamine supplementation on glycaemic outcomes in patients with T2DM.MethodsEligibility criteria: Studies that assessed effect of thiamine supplementation in adults with T2DM which measured glycaemic outcomes—HbA1c, fasting blood glucose (FBG) and/or postprandial blood glucose (PPG) were included. Information sources: PUBMED, Tripdatabase, the Cochrane Central Register, National Institute of Health Clinical Database and Google Scholar were searched until December 2021 for RCTs. Risk of bias: It was assessed using standardised critical appraisal instruments from the Joanna Briggs Institute for RCTs. Synthesis of results: Where possible, studies were pooled in a meta-analysis. Results were presented in a narrative format if statistical pooling was not possible.ResultsIncluded studies: Six trials involving 364 participants. Synthesis of results: No significant beneficial effects were observed on glycaemic outcomes with 100–900 mg/day of thiamine or benfotiamine for up to 3 months (HbA1c: MD, −0.02%, 95% CI: −0.35 to 0.31; FBG: MD,−0.20 mmol/L; 95% CI: −0.69 to 0.29; PPG: MD, – 0.20 mmol/L, 95% CI: −2.05 to 1.65 (mean difference, MD)). There was a significant increase in high-density lipoprotein (HDL) (MD, 0.10; 95% CI: 0.10 to 0.20) at 3-month follow-up. Benfotiamine reduced triglyceride level (MD, −1.10; 95% CI: −1.90 to –0.30) in 120 mg/day dose as compared with placebo 150 mg/day, however this was not demonstrated in higher doses.DiscussionLimitations of evidence: Inclusion of single-centre trials published only in English, small sample sizes of included studies, lack of trials investigating outcomes for same comparisons and varying follow-up periods. Interpretation: Thiamine supplementation does not affect glycaemic outcomes, however reduces triglycerides while increasing HDL. Multicentre well-designed RCT with higher doses of thiamine and a follow-up period of 1–2 years will provide better evidence.PROSPERO registration numberCRD42020170520.
Effect of hand versus electronic signatures on response rates in postal surveys: a randomised controlled trial among emergency physicians in Canada
Authors: Patel Dilan , Taljaard Monica , Yadav Krishan , Hickey Michael , Perry Jeffrey J 
Published: August 2022

ObjectivesHand signatures offer a more authentic personalisation, which carries over to a sense of trust, although are costly and time-consuming when considering large postal surveys. The objective of this study was to compare response rates when using either hand-signed or electronic-signed letters in a postal survey.Design and settingWe embedded this randomised controlled trial within a national cross-sectional postal survey of emergency physicians in Canada. The survey aimed to describe current practice patterns with respect to primary headache disorders.ParticipantsWe randomly sampled 500 emergency physicians listed in the Scott’s Canadian Medical Directory, 2019 edition.InterventionsUsing computer-generated random numbers, physicians were allocated to receiving either hand-signed (n=250) or electronic signed (n=250) letters. The initial mailout contained a US$5 Tim Hortons coffee card with the invitation letter. Four reminders were sent to non-responders every 3 weeks. The same type of signature was used for the initial invitation and subsequent reminders.OutcomeThe primary outcome was the survey response rate.ResultsAmong 500 physicians invited, 32 invitations were undeliverable. Among the remaining 468 physicians, 231 had been allocated to the hand-signed group and 237 to the electronic signed group. The response rate in the hand-signed group was 87 (37.7%) vs 97 (40.9%) in the electronic-signed group (absolute difference in proportions −3.3%, 95% CI −12.1% to 5.6%).ConclusionThere was no significant difference in physician response rate between hand-signed and e-signed cover letter and reminder letters. Electronic signatures should be used in future postal surveys among physicians to save on time and labour without impacting response rates.
‘We are data rich but information poor’: how do patient-reported measures stimulate patient involvement in quality improvement interventions in Swedish hospital departments?
Authors: Bergerum Carolina , Petersson Christina , Thor Johan , Wolmesjö Maria 
Published: August 2022

ObjectiveThis study aimed to investigate if and how patient-reported measures from national and local monitoring stimulate patient involvement in hospital quality improvement (QI) interventions. We were also interested in the factors that influence the level and degree of patient involvement in the QI interventions.MethodsThe study used a qualitative, descriptive design. Inspired by the Framework Method, we created a working analytical framework. Four hospital departments participated in the data collection. Collaborating with a QI leader from each department, we identified the monitoring systems for the patient-reported measures that were used to initiate or evaluate QI interventions. Thereafter, the level and degree of patient involvement and the factors that influenced this involvement were analysed for all QI interventions. Data were mapped in an Excel spreadsheet to analyse connections and differences.ResultsDepartments used patient-reported measures from both national and local monitoring systems to initiate or evaluate their QI interventions. Thirty-one QI interventions were identified and analysed. These interventions were mainly conducted at the direct care and organisational levels. By participating in questionnaires, patients were involved to the degree of consultation. Patients were not involved to the degree of partnership and shared leadership for the identified QI interventions.ConclusionsOverall, hospital departments have limited knowledge regarding patient-reported measures and how they are best applied in QI interventions and how they support improvements. Applying patient-reported measures to hospital QI interventions does not enhance patient involvement beyond the degree of consultation.
Phase II study of durvalumab (anti-PD-L1) and trametinib (MEKi) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC)
Authors: Johnson Benny , Haymaker Cara L , Parra Edwin R , Soto Luisa Maren Solis , Wang Xuemei , Thomas Jane V , Dasari Arvind , Morris Van K , Raghav Kanwal , Vilar Eduardo , Kee Bryan K , Eng Cathy , Parseghian Christine M , Wolff Robert A , Lee Younghee , Lorenzini Daniele , Laberiano-Fernandez Caddie , Verma Anuj , Lang Wenhua , Wistuba Ignacio I , Futreal Andrew , Kopetz Scott , Overman Michael J 
Published: August 2022

BackgroundMonotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells.MethodsOpen-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126). T is 2 mg/day orally starting 1 week prior to D, which is given 1500 mg intravenously every 4 weeks. Simon 2-stage design used to enroll 29 pts into first stage, requiring a response in two or more pts to proceed to stage 2. Tumor biopsies were collected at baseline (BL) and early on-treatment (OT) at week 4.ResultsTwenty nine treated pts include 48% females, median age 48 years (range 28–75), and median prior therapies 2 (range 1–5). No grade (G) 4 or 5 treatment-related adverse events (TRAE). The most common TRAE of any grade was acneiform rash, 17% being G3. One of 29 pts had confirmed partial response (PR) lasting 9.3 months (mo) for an overall response rate of 3.4%. Seven pts had stable disease (SD) and five pts (1 PR, 4 SD) demonstrated decrease in total carcinoembryonic antigen ng/mL (best percentage reduction: 94%, 95%, 42%, 34%, and 22%, respectively). Median progression-free survival was 3.2 mo (range 1.1–9.3 months). Three pts with both liver and lung metastases demonstrated discrepant responses in which clinical benefit was present in the lung metastases but not liver metastases. Comparison of BL and 4-week OT tumor tissue flow cytometry demonstrated no changes in T-cell infiltration but upregulation expression of PD-1 and Tim3 on CD8 T cells. However, expression of PD-1 and Tim3 as single markers and as coexpressed markers was observed to increase OT relative to BL (p=0.03, p=0.06 and p=0.06, respectively).ConclusionsT+D demonstrated acceptable tolerability in pts with refractory MSS mCRC. The response rate in the first stage of the study did not meet efficacy criteria to proceed to the second stage. Specific site of metastatic disease may impact outcomes in novel immunotherapy combination trials.Trial registration numberNCT03428126.
Multicenter investigation of technical and clinical outcomes after thrombectomy for distal vessel occlusion by frontline technique
Authors: Alawieh Ali M , Chalhoub Reda M , Al Kasab Sami , Jabbour Pascal , Psychogios Marios-Nikos , Starke Robert M , Arthur Adam S , Fargen Kyle M , De Leacy Reade , Kan Peter , Dumont Travis M , Rai Ansaar , Crosa Roberto Javier , Maier Ilko , Goyal Nitin , Wolfe Stacey Q , Cawley C Michael , Mocco J , Tjoumakaris Stavropoula I , Howard Brian M , Dimisko Laurie , Saad Hassan , Ogilvy Christopher S , Crowley R Webster , Mascitelli Justin R , Fragata Isabel , Levitt Michael R , Kim Joon-tae , Park Min S , Gory Benjamin , Polifka Adam J , Matouk Charles , Grossberg Jonathan A , Spiotta Alejandro M 
Published: August 2022

BackgroundEndovascular thrombectomy (EVT) is the standard-of-care for proximal large vessel occlusion (LVO) stroke. Data on technical and clinical outcomes in distal vessel occlusions (DVOs) remain limited.MethodsThis was a retrospective study of patients undergoing EVT for stroke at 32 international centers. Patients were divided into LVOs (internal carotid artery/M1/vertebrobasilar), medium vessel occlusions (M2/A1/P1) and isolated DVOs (M3/M4/A2/A3/P2/P3) and categorized by thrombectomy technique. Primary outcome was a good functional outcome (modified Rankin Scale ≤2) at 90 days. Secondary outcomes included recanalization, procedure-time, thrombectomy attempts, hemorrhage, and mortality. Multivariate logistic regressions were used to evaluate the impact of technical variables. Propensity score matching was used to compare outcome in patients with DVO treated with aspiration versus stent retrieverResultsWe included 7477 patients including 213 DVOs. Distal location did not independently predict good functional outcome at 90 days compared with proximal (p=0.467). In distal occlusions, successful recanalization was an independent predictor of good outcome (adjusted odds ratio (aOR) 5.11, p<0.05) irrespective of technique. Younger age, bridging therapy, and lower admission National Institutes of Health Stroke Scale (NIHSS) were also predictors of good outcome. Procedure time ≤1 hour or ≤3 thrombectomy attempts were independent predictors of good outcomes in DVOs irrespective of technique (aOR 4.5 and 2.3, respectively, p<0.05). There were no differences in outcomes in a DVO matched cohort of aspiration versus stent retriever. Rates of hemorrhage and good outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group and attempts in the stent retriever group.ConclusionsOutcomes following EVT for DVO are comparable to LVO with similar results between techniques. Techniques may exhibit different futility metrics; stent retriever thrombectomy was influenced by attempts whereas aspiration was more dependent on procedure time.
Knowledge and attitude regarding organ donation among medical students in Hong Kong: a cross-sectional study
Authors: Chu Steven Tsun-Wai , Chung Phoebe Pui Wun , Hui Yau Long , Choi Hing Chung , Lam Hiu Wai , Sin Ling Ling , Law Chui Shan , Yan Nga Ying , Choi Ka Yung , Wan Eric Yuk Fai 
Published: August 2022

Abstract

Objectives
The rate of organ donation in Hong Kong is among the lowest in developed regions. Since medical students will play an important role in counselling patients for organ donation and identifying potential donors in the future, their knowledge, attitudes and action for organ donation are important. This study aims to understand knowledge, attitudes and actions with regard to organ donation among medical students and investigate the factors determining the knowledge and attitudes.

Design
A cross-sectional study.

Setting and participants
Medical students in Hong Kong were invited to complete a questionnaire. 377 medical students participated in the study.

Methods
The questionnaire assessed their attitudes, knowledge, action of organ donation, belief and perception on organ donation, and other factors. Linear regression analyses and logistic regression were performed to analyse the effect of the variables on knowledge, attitudes and action for organ donation.

Results
Almost all medical students (99.5%) held a positive attitude towards organ donation, but only 28.1% have signed up as organ donors. Determinants of knowledge of organ donation included belief in preservation of intact body after death (β = –0.14, 95% CI = –0.24 to –0.04) and perceived confidence and competence of organ donation discussion (β = –0.12, 95% CI = –0.22 to –0.02). Predictors of organ donor registration status included knowledge of organ donation (OR=1.03, 95% CI=1.00 to 1.06), perceived convenience of organ donation registration (OR=3.75, 95% CI=1.62 to 8.71), commitment to organ donation (OR=3.81, 95% CI=2.01 to 7.21) and exposure to organ donation (OR=4.28, 95% CI=2.37 to 7.74).

Conclusions
Knowledge is positively associated with organ donation action. The above determinants of organ donation could be emphasised in medical education.
Changes in the Neuropeptide Y mRNA Expression in Oncorhynchus mykiss at Different Feeding Frequencies
Authors: Nahayat Mozhdeh , Zakeri Mohammad , Salati Amir Parviz , Qasemi Seyed Ahmad 
Published: August 2022

In this study, the relationship between feeding time preference and appetite in Oncorhynchus mykiss with scheduled feeding frequencies was investigated using neuropeptide Y (NPY). Samples (

n
=
288

, initial weight:

38.72
±
2.99

g) were stocked in three treatments of different feeding frequencies with six replications. Treatments included one feeding time at 09:00 (T1), three feeding times at 09:00, 13:00, and 17:00 (T2), and five feeding times at 09:00, 11:00, 13:00, 15:00, and 17:00 (T3) every day based on 5% of body weight for 30 days. On day 31, each experimental treatment was divided into fed and unfed groups with triplicates. To measure NPY expression, fish were sampled from both groups 15 minutes earlier than feeding hours. In a comparison of the NPY expression in T1 of the fed group, the highest level of NPY occurred at 08:45. In T2, the NPY was maximized at 08:45, 12:45, and 16:45. In T3, the NPY increased significantly at 08:45 compared to the other sampling hours. In T1 and T2 of the unfed group, the highest NPY was recorded at 10:45 and 14:45, respectively. In T3, upward and downward changes in the NPY were observed from 08:45 to 12:45 and from 12:45 to 16:45, respectively. Concerning changes in the NPY levels, the fed groups in the three treatments were significantly different at all hours, except for 08:45. In the unfed groups, significant differences were recorded between the treatments at 10:45 and 14:45. According to the fish appetite, it can be concluded that feeding O. mykiss three times a day at about 4 h intervals may be appropriate.
The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer
Authors: Choi Yun Jung , Kim Da-Som , Sung Young Hoon , Kim Dong Ha , Im Kyungtaek , Lee Hyeonjeong , Lee Chae Won , Cho Jeongin , Min Joongkee , Woo Dong-Cheol , Kim Sung-Eun , Lee Sunho , Kong Yun Jeong , Ryu Hyung Chul , Kim Jae-Sun , Rengasamy Rajesh , Ji Wonjun , Choi Chang-Min , Lee Jae Cheol , Rho Jin Kyung 
Published: August 2022

Abstract

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC.

Significance:
OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.