bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial fibrillation and mortality in outpatients with heart failure in Tanzania: a prospective cohort study
Authors: Chen Yunchan , Alphonce Emmanuel , Mujuni Eva , Kisigo Godfrey A , Kingery Justin R , Makubi Abel , Peck RN , Kalokola Fredrick 
Published: January 2022

ObjectiveIn recent years, the prevalence and mortality of heart failure (HF) and other associated cardiovascular diseases have doubled in sub-Saharan Africa (SSA). Studies in high-income countries indicate that HF with concurrent atrial fibrillation (AF) is linked to increased mortality. Our objective was to determine the incidence and clinical outcomes of AF among patients with HF in SSA.DesignA prospective cohort study using data collected between October 2018 and May 2020.SettingOutpatient clinic at a tertiary hospital in Mwanza, Tanzania.Participants303 adult participants (aged ≥18 years) with HF as defined by the European Society of Cardiology guidelines (2016) and 100 adults with HF as defined by clinical criteria alone were enrolled into the study. Patients with comorbid medical condition that had prognosis of <3 months (ie, advance solid tumours, advance haematological malignancies) were excluded.MethodsParticipants were screened for AF, and their medical history, physical examinations and sociodemographic information were obtained. Multivariable logistic regression models were used to examine factors associated with AF incidence. Cox regression models were used to analyse 3-month mortality and its associated risk factors.ResultsWe enrolled 403 participants with HF (mean age 60±19 years, 234 (58%) female). The AF prevalence was 17%. In multivariable models, factors associated with AF were low income, alcohol consumption and longer duration of HF. At the end of the 3-month follow-up, 120 out of 403 (30%) participants died, including 44% (31/70) of those with AF. Higher heart rate on ECG, more severe New York Heart Association HF class, rural residence and anaemia were significantly correlated with mortality.ConclusionAF is common, underdiagnosed and is associated with significant mortality among outpatients with HF in Tanzania (HR 1.749, 95% CI 1.162 to 2.633, p=0.007). Our findings additionally identify tachycardia (>110 bpm, HR 1.879, 95% CI 1.508 to 2.340, p<0.001) as an easily measurable, high-impact physical examination finding for adverse outcomes in patients with HF.
Impact of unacceptable behaviour between healthcare workers on clinical performance and patient outcomes: a systematic review
Authors: Guo Linda , Ryan Benjamin , Leditschke Isabel Anne , Haines Kimberley J , Cook Katrina , Eriksson Lars , Olusanya Olusegun , Selak Tanya , Shekar Kiran , Ramanan Mahesh 
Published: January 2022

BackgroundRecent studies suggest that displays of unacceptable behaviour, including bullying, discrimination and harassment, between healthcare workers (HCWs) may impair job performance, and in turn, increase the frequency of medical errors, adverse events and healthcare-related complications. The objective of this systematic review was to summarise the current evidence of the impact of unacceptable behaviour occurring between HCWs on clinical performance and patient outcomes.MethodsWe searched MEDLINE, Embase, PsycINFO and CINAHL from 1 January 1990 to 31 March 2021. The search results were screened by two independent reviewers and studies were included if they were original research that assessed the effects of unacceptable behaviour on clinical performance, quality of care, workplace productivity or patient outcomes. Risk of bias was assessed using tools relevant to the study design and the data were synthesised without meta-analysis.ResultsFrom the 2559 screened studies, 36 studies were included: 22 survey-based studies, 4 qualitative studies, 3 mixed-methods studies, 4 simulation-based randomised controlled trials (RCTs) and 3 other study designs. Most survey-based studies were low quality and demonstrated that HCWs perceived a relationship between unacceptable behaviour and worse clinical performance and patient outcomes. This was supported by a smaller number of higher quality retrospective studies and RCTs. Two of four RCTs produced negative results, possibly reflecting inadequate power or study design limitations. No study demonstrated any beneficial effect of unacceptable behaviour on the study outcomes.ConclusionsDespite the mixed quality of evidence and some inconsistencies in the strengths of associations reported, the overall weight of evidence shows that unacceptable behaviour negatively affects the clinical performance of HCWs, quality of care, workplace productivity and patient outcomes. Future research should focus on the evaluation and implementation of interventions that reduce the frequency of these behaviours.
Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations
Authors: Pollyea Daniel A. , DiNardo Courtney D. , Arellano Martha L. , Pigneux Arnaud , Fiedler Walter , Konopleva Marina , Rizzieri David A. , Smith B. Douglas , Shinagawa Atsushi , Lemoli Roberto M. , Dail Monique , Duan Yinghui , Chyla Brenda , Potluri Jalaja , Miller Catherine L. , Kantarjian Hagop M. 
Published: January 2022

Abstract

Purpose:
To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).

Patients and Methods:
Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1–28) and azacitidine (75 mg/m2; days 1–7/28-day cycle).

Results:
In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group.

Conclusions:
Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.
See related commentary by Perl and Vyas, p. 2719
FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma
Authors: Sharma Poornima , Kanapuru Bindu , George Bindu , Lin Xue , Xu Zhenzhen , Bryan Wilson W. , Pazdur Richard , Theoret Marc R. 
Published: January 2022

Abstract

In March 2021, the FDA approved idecabtagene vicleucel, a chimeric antigen receptor T-cell therapy targeting the B-cell maturation antigen (BCMA), for adult patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 mAb. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DOR) in 100 adult patients with RRMM treated with idecabtagene vicleucel in a single-arm trial. Patients received a single infusion of idecabtagene vicleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Of the 100 patients in the efficacy evaluable population, ORR was 72% [95% confidence interval (CI), 62–81] with stringent CR rate of 28% (95% CI, 19–38). After median follow-up of 10.7 months, median DOR was 11 months (95% CI, 10.3–11.4) in responders (partial response or better) and 19 months [95% CI, 11.4 months, not estimable (NE)] in patients who achieved stringent CR. Serious adverse reactions occurred in 67% of 127 patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 9% and 4%, respectively, leading to a Risk Evaluation and Mitigation Strategy. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4%, with two fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% (3/127), with two fatalities.
Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants
Authors: Hofmann Marco H. , Gerlach Daniel , Misale Sandra , Petronczki Mark , Kraut Norbert 
Published: January 2022

Abstract

KRAS is the most frequently mutated oncogene, harboring mutations in approximately one in seven cancers. Allele-specific KRASG12C inhibitors are currently changing the treatment paradigm for patients with KRASG12C-mutated non–small cell lung cancer and colorectal cancer. The success of addressing a previously elusive KRAS allele has fueled drug discovery efforts for all KRAS mutants. Pan-KRAS drugs have the potential to address broad patient populations, including KRASG12D-, KRASG12V-, KRASG13D-, KRASG12R-, and KRASG12A-mutant or KRAS wild-type–amplified cancers, as well as cancers with acquired resistance to KRASG12C inhibitors. Here, we review actively pursued allele-specific and pan-KRAS inhibition strategies and their potential utility.

Significance:
Mutant-selective KRASG12C inhibitors target a fraction (approximately 13.6%) of all KRAS-driven cancers. A broad arsenal of KRAS drugs is needed to comprehensively conquer KRAS-driven cancers. Conceptually, we foresee two future classes of KRAS medicines: mutant-selective KRAS drugs targeting individual variant alleles and pan-KRAS therapeutics targeting a broad range of KRAS alterations.
RAS at 40: Update from the RAS Initiative
Authors: Nissley Dwight V. , McCormick Frank 
Published: January 2022

Summary:
The RAS Initiative was launched in 2013 to address unmet clinical needs of patients with KRAS-driven cancers. The Initiative is based at Frederick National Laboratory for Cancer Research in Frederick, MD, and involves multiple collaborations with the RAS research community in academia and industry with the shared goal of developing RAS therapies.
Post–ST‐Segment–Elevation Myocardial Infarction Platelet Reactivity Is Associated With the Extent of Microvascular Obstruction and Infarct Size as Determined by Cardiac Magnetic Resonance Imaging
Authors: Massalha Eias , Oren Daniel , Goitein Orly , Brodov Yafim , Fardman Alex , Younis Anan , Berkovitch Anat , Raibman‐Spector Shir , Konen Eli , Maor Elad , Fefer Paul , Segev Amit , Beigel Roy , Matetzky Shlomi 
Published: January 2022

Background
Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST‐segment–elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO.

Methods and Results

We prospectively evaluated 105 patients in 2 distinct periods (2012–2013 and 2016–2018) who presented with first ST‐segment–elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was defined as hyporesponsiveness to either aspirin or P2Y12 receptor inhibitor agents and demonstrated in 31 patients (29.5%) of the current cohort. Suboptimal platelet response to DAPT was associated with a significantly greater extent of MVO when expressed as a percentage of the left ventricular mass, left ventricular scar, and the number of myocardial left ventricular segments showing MVO (
P
<0.01 for each). Adjusted multivariable logistic regression model revealed that suboptimal response to DAPT is significantly associated with both greater late gadolinium enhancement (
P
<0.01) and MVO extent (odds ratio, 3.7 [95% CI, 1.3–10.5];
P
=0.01). Patients with a greater extent of MVO were more likely to sustain major adverse cardiovascular events at a 1‐year follow‐up (37% versus 11%;
P
<0.01).

Conclusions
In patients undergoing primary percutaneous coronary intervention for ST‐segment–elevation myocardial infarction, platelet reactivity in response to DAPT is a key predictor of the extent of both myocardial and microvascular damage.
Childhood Blood Pressure, Carotid Intima Media Thickness, and Distensibility After In Utero Exposure to Gestational Hypertensive Disorders
Authors: Wiertsema Clarissa J. , Jaddoe Vincent W. V. , Mulders Annemarie G. M. G. J. , Gaillard Romy 
Published: January 2022

Background
Offspring exposed to gestational hypertensive disorders have higher blood pressure and increased risk of stroke in later life. Gestational hypertensive disorders might influence vascular development in the offspring, predisposing them to a higher blood pressure and stroke in later life.

Methods and Results

In a population‐based cohort among 4777 mother–offspring pairs, we examined whether gestational hypertension, preeclampsia, and higher gestational blood pressure across the full blood pressure spectrum were associated with offspring blood pressure, carotid intima media thickness, and distensibility at the age of 10 years. Offspring exposed to gestational hypertension, but not preeclampsia, had higher systolic and diastolic blood pressure (0.17 [95% CI, 0.02–0.31] and 0.23 [95% CI, 0.08–0.38] increases in standard deviation scores, respectively), whereas no associations with intima media thickness and distensibility were present. Higher maternal systolic and diastolic blood pressure in early, mid, and late pregnancy were associated with higher offspring systolic and diastolic blood pressure and lower distensibility (
P
values <0.05), but not with intima media thickness. The associations were not explained by maternal, birth, or child factors. Paternal systolic and diastolic blood pressure were also associated with these offspring outcomes (
P
values <0.05), with a comparable strength as maternal–offspring associations.

Conclusions
Gestational hypertension and higher gestational blood pressure, even below the diagnostic threshold for gestational hypertensive disorders, are associated with higher offspring blood pressure and lower carotid distensibility. No associations were found for preeclampsia with offspring vascular outcomes. As maternal–offspring and paternal–offspring associations were comparable, these associations are more likely driven by genetic predisposition and shared lifestyle rather than by a direct intrauterine effect.
Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients
Authors: Johnstone Mark S , Miller Gillian , Pang Grace , Burton Paul , Kourounis Georgios , Winter Jack , Crighton Emilia , Mansouri David , Witherspoon Paul , Smith Karen , McSorley Stephen T 
Published: January 2022

Background The faecal immunochemical test (FIT) has proven utility for colorectal cancer detection in symptomatic patients. However, most patients with a raised faecal haemoglobin (f-Hb) do not have colorectal cancer. We investigated alternative diagnoses and demographics associated with a raised f-Hb in symptomatic patients. Methods A retrospective, observational study was performed of patients with FIT submitted between August 2018 to January 2019 in NHS Greater Glasgow and Clyde followed by colonoscopy. Colonoscopy/pathology reports were searched for alternative diagnoses. Covariables were compared using the χ 2 test. Multivariate binary logistic regression identified independent predictors of a raised f-Hb. Results 1272 patients were included. In addition to colorectal cancer (odds ratio (OR), 9.27 (95% confidence interval (CI): 3.61–23.83; p < 0.001)), older age (OR, 1.52 (95% CI: 1.00–2.32; p = 0.05)), deprivation (OR, 1.54 (95% CI: 1.21–1.94; p < 0.001)), oral anticoagulants (OR, 1.78 (95% CI: 1.01–3.15; p = 0.046)), rectal bleeding (OR, 1.47 (95% CI: 1.15–1.88; p = 0.002)), advanced adenoma (OR, 7.52 (95% CI: 3.90–14.49; p < 0.001)), non-advanced polyps (OR, 1.78 (95% CI: 1.33–2.38; p < 0.001)) and inflammatory bowel disease (IBD) (OR, 4.19 (95% CI: 2.17–8.07; p < 0.001)) independently predicted raised f-Hb. Deprivation (Scottish Index of Multiple Deprivation (SIMD) 1-2: OR, 2.13 (95% CI: 1.38–3.29; p = 0.001)) independently predicted a raised f-Hb in patients with no pathology found at colonoscopy. Conclusions An elevated f-Hb is independently associated with older age, deprivation, anticoagulants, rectal bleeding, advanced adenoma, non-advanced polyps and IBD in symptomatic patients. Deprivation is associated with a raised f-Hb in the absence of pathology. This must be considered when utilising FIT in symptomatic patients.
Impact of Delay on Hospitalization in Older Patients With Head and Neck Cancer: A Multicenter Study
Authors: Schoonbeek Rosanne C. , Festen Suzanne , Rashid Roza , van Dijk Boukje A.C. , Halmos György B. , van der Velden Lilly‐Ann 
Published: January 2022

ObjectiveTo assess the impact of delay in treatment initiation on hospitalization, overall survival, and recurrence in older patients with head and neck cancer (HNC).Study DesignRetrospective multicenter study.SettingTwo tertiary referral centers.MethodsAll patients with newly diagnosed HNC (≥60 years) treated between 2015 and 2017 were retrospectively included. Time‐to‐treatment intervals were assessed (ie, calendar days between first visit and start of treatment). Multiple multivariable models were performed with hospital admission days (>14 days), survival, and recurrence as dependent outcome variables.ResultsIn total, 525 patients were enrolled. The mean age was 70.7 years and 70.7% were male. Median time to treatment was 34.0 days, and 36.3% started treatment within 30 days (P =. 576 between centers). Patients with radiotherapy had longer time to treatment than surgical patients (39.0 vs 29.0 days, P <. 001). Current smoking status, stage IV tumors, and definitive radiotherapy were significantly associated with delay in the multivariable analysis. Time‐to‐treatment interval ≥30 days was a significant predictor of longer hospital admission (>14 days) in the first year after treatment in an adjusted model (odds ratio, 4.66 [95% CI, 2.59‐8.37]; P <. 001). Delay in treatment initiation was not associated with overall survival or tumor recurrence.ConclusionThis study highlights the importance and challenges of ensuring timely treatment initiation in older patients with HNC, as treatment delay was an independent predictor of hospitalization. During oncologic workup, taking time to consider patient‐centered outcomes (including minimizing time spent in hospital) while ensuring timely start of treatment requires well‐structured, fast‐track care pathways.
A Systematic Literature Review of Health Utility Values in Breast Cancer
Authors: Kaur Manraj N. , Yan Jiajun , Klassen Anne F. , David Justin P. , Pieris Dilshan , Sharma Manraj , Bordeleau Louise , Xie Feng 
Published: January 2022

Background Health utility values (HUVs) are important inputs to the cost-utility analysis of breast cancer interventions. Purpose Provide a catalog of breast cancer–related published HUVs across different stages of breast cancer and treatment interventions. Data Sources Systematic searches of MEDLINE, MEDLINE In-Process, EMBASE, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases (2005–2017). Study Selection Studies published in English that reported mean or median HUVs using direct or indirect methods of utility elicitation for breast cancer. Data Extraction Independent reviewers extracted data on a preestablished and piloted form; disagreements were resolved through discussion. Data Analysis Mixed-effects meta-regression using restricted maximum likelihood modeling was conducted for intervention type, stage of breast cancer, and typical clinical and treatment trajectory of breast cancer patients to assess the effect of study characteristics (i.e., sample size, utility elicitation method, and respondent type) on HUVs. Data Synthesis Seventy-nine studies were included in the review. Most articles ( n = 52, 66%) derived HUVs using the EQ-5D. Patients with advanced-stage breast cancer (range, 0.08 to 0.82) reported lower HUVs as compared with patients with early-stage breast cancer (range, 0.58 to 0.99). The meta-regression analysis found that undergoing chemotherapy and surgery and radiation, being diagnosed with an advanced stage of breast cancer, and recurrent cancer were associated with lower HUVs. The members of the general public reported lower HUVs as compared with patients. Limitations There was considerable heterogeneity in the study population, health states assessed, and utility elicitation methods. Conclusion This review provides a catalog of published HUVs related to breast cancer. The substantial heterogeneity in the health utility studies makes it challenging for researchers to choose which HUVs to use in cost-utility analyses for breast cancer interventions.
The complementarity of control formalization and control flexibility: The contingent effects of competitive turbulence
Authors: Yang Feifei , Shinkle George A , Goudsmit Mirjam 
Published: January 2022

We examine how the complementarity of control formalization and control flexibility influences organizational performance across contexts of varying competitive turbulence. We build contingency arguments anchored in the efficiency logic of control theory and investigate both the restrictive and facilitative views of control formalization. Our empirical evidence is based on a survey of top executives from 536 organizations across the United States, Australia, China, and Israel. We find that control formalization and control flexibility are complementary in environments of low competitive turbulence. With increasing turbulence, the complementarity diminishes and shifts toward substitutive effects.JEL Classification: L2