bluuebunny/crossref_metadata_2025_split huggingface dataset:
Days alive and at home after hip fracture: a cross-sectional validation of a patient-centred outcome measure using routinely collected data
Authors: McIsaac Daniel I , Talarico Robert , Jerath Angela , Wijeysundera Duminda N 
Published: July 2021

BackgroundDays alive and at home (DAH) is a patient centered outcome measureable in routinely collected health data. The validity and minimally important difference (MID) in hip fracture have not been evaluated.ObjectiveWe assessed construct and predictive validity and estimated a MID for the patient-centred outcome of DAH after hip fracture admission.MethodsThis is a cross-sectional observational study using linked health administrative data in Ontario, Canada. DAH was calculated as the number of days alive within 90 days of admission minus the number of days hospitalised or institutionalised. All hospital admissions (2012–2018) for hip fracture in adults aged >50 years were included. Construct validity analyses used Bayesian quantile regression to estimate the associations of postulated patient, admission and process-related variables with DAH. The predictive validity assessed was the correlation of DAH in 90 days with the value from 91 to 365 days; and the association and discrimination of DAH in 90 days predicting subsequent mortality. MID was estimated by averaging distribution-based and clinical anchor-based estimates.ResultsWe identified 63 778 patients with hip fracture. The median number of DAH was 43 (range 0–87). In the 90 days after admission, 8050 (12.6%) people died; a further 6366 (10.0%) died from days 91 to 365. Associations between patient-level and admission-level factors with the median DAH (lower with greater age, frailty and comorbidity, lower if admitted to intensive care or having had a complication) supported construct validity. DAH in 90 days after admission was strongly correlated with DAH in 365 days after admission (r=0.922). An 11-day MID was estimated.ConclusionDAH has face, construct and predictive validity as a patient-centred outcome in patients with hip fracture, with an estimated MID of 11 days. Future research is required to include direct patient perspectives in confirming MID.
Iron deficiency in patients with cancer: a prospective cross-sectional study
Authors: Luporsi Elisabeth , Turpin Anthony , Massard Vincent , Morin Sophie , Chauffert Bruno , Carnot Aurélien , Cacoub Patrice 
Published: July 2021

BackgroundDespite the deleterious consequences of iron deficiency (ID) in patients with cancer, underdiagnosis is frequent. The CARENFER study aimed to assess the prevalence of ID using both serum ferritin concentration and transferrin coefficient saturation (iron-saturation of transferrin, TSAT) index, as well as ID anaemia in patients with cancer.MethodsThis prospective cross-sectional study was conducted in 15 oncology units in France in 2019. All patients present in the medical unit during the 2-week study period, regardless of the type of tumour (solid or haematological) and treatment, were eligible. Serum ferritin concentration, TSAT index and haemoglobin level were determined. ID and ID-associated anaemia were defined according to European Society of Medical Oncology 2018 Guidelines: ID was defined either as ferritin <100 µg/L (absolute ID) or as ferritin ≥100 µg/L and TSAT <20% (functional ID).ResultsA total of 1221 patients with different types of solid malignant tumours were analysed: median age 64 years; 89.4% under treatment for their cancer, mainly by chemotherapy (75.4%). Overall, ID was found in 57.9% (55.1–60.6) of patients. Among them, functional ID accounted for 64% of cases. ID anaemia was reported in 21.8% (19.6–24.2) of all patients with cancer. ID was highly prevalent in untreated (75/130, 57.4%) and non-anaemic (419/775, 54.1%) patients.ConclusionThis study highlights the high prevalence of ID in patients with cancer, whether or not associated with anaemia or treatment. These results emphasise the need to a better detection and management of ID in cancer, thereby optimising overall patient care.Trial registration numberClinicalTrials.gov Identifier:NCT03924271.
Efficacy and sustainability of dialectical behaviour therapy for inpatient adolescents: a follow-up study
Authors: Tebbett-Mock Alison Ann , McGee Madeline , Saito Ema 
Published: July 2021

BackgroundDialectical behaviour therapy (DBT) is an evidence-based treatment for adolescents targeting suicidal and non-suicidal self-injurious behaviours. Research supports DBT’s efficacy in inpatient settings, but implementation and sustainability are understudied.AimsThis study is a follow-up of a previous study by Tebbett-Mocket aland examines the efficacy and sustainability of an adolescent DBT inpatient unit within a psychiatric hospital in the Northeast. We hypothesised that adolescents who received DBT in our follow-up group (DBT Group 2) would not have statistical difference (ie, greater or fewer) of the following compared with the first group of patients who received DBT on the unit the year prior (DBT Group 1) and would have significantly fewer of the following compared with the treatment as usual (TAU) group: (1) constant observation hours for suicidal ideation, self-injury and aggression; (2) incidents of suicide attempts, self-injury and aggression; (3) restraints; (4) seclusions; (5) days hospitalised; (6) times readmitted to the unit within 30 days of discharge.MethodsWe conducted a retrospective chart review for adolescents receiving inpatient DBT (DBT Group 1, n=425; DBT Group 2, n=393) and a historical control group (TAU, n=376). The χ2tests and one-way analysis of variance were conducted as preliminary analyses to examine group differences on diagnosis, gender and age. Kruskal-Wallis H tests were conducted to examine group differences on outcomes. Mann-Whitney U tests were used as post hoc analyses.ResultsPatients in DBT Group 2 were comparable to DBT Group 1 for the number of constant observation hours for self-injury (U=83 432.50, p=0.901), restraints (U=82 109, p=0.171) and days hospitalised (U=83 438.5, p=0.956). Patients in DBT Group 2 had a significantly greater number of incidents of suicide attempts compared with DBT Group 1 (U=82 662.5, p=0.037) and of self-injury compared with patients in DBT Group 1 (U=71724.5, p<0.001) and TAU (U=65649.0, p<0.001).ConclusionsResults provide support for adolescent inpatient DBT compared with TAU and highlight staff turnover and lack of training as potential barriers to sustainability and efficacy.
Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial
Authors: Monga Varun , Miller Benjamin J , Tanas Munir , Boukhar Sarag , Allen Bryan , Anderson Carryn , Stephens Laura , Hartwig Stacey , Varga Steven , Houtman Jon , Wang Lei , Zhang Weizhou , Jaber Omar , Thomason Jon , Kuehn David , Rajput Maheen , Metz Catherine , Zamba K.D. , Mott Sarah , Abanonu Chinemerem , Bhatia Sudershan , Milhem Mohammed 
Published: July 2021

BackgroundSoft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical studies, oncolytic virotherapy in sarcoma has demonstrated antitumor effects via direct intratumoral oncolysis and cytotoxic T-cell–mediated immune responses. Talimogene laherparepvec (TVEC) is a replication-competent, immune-enhanced, oncolytic herpes simplex virus type 1 engineered for intratumoral injection; it has been approved by the FDA for the treatment of locally advanced and metastatic melanoma.MethodsWe explored a novel combination of TVEC with standard-of-care EBRT administered preoperatively in patients with locally advanced STS of the extremities and trunk in a phase IB/II clinical trial. Thirty patients with primary STS >5 cm for which EBRT was indicated to achieve negative margins were enrolled. FDA-approved TVEC doses were used. Immune correlative studies in peripheral blood, biopsy and resected tumor tissues were performed.ResultsNo dose-limiting toxicity was observed. Adverse events were similar to those reported in prior studies with TVEC. One patient with myxoid liposarcoma exhibited a partial response. Seven of the 29 (24%) evaluable patients achieved 95% pathological necrosis. None of the patients developed a herpes infection due to the treatment. Eight of the 29 (27%) patients developed postoperative wound complications, which is consistent with previous studies. None of the patients developed local recurrence after surgical resection of the primary sarcoma. 2-year progression-free and overall survival were 57% and 88%, respectively. Caspase-3 demonstrated increased expression of both in TVEC-treated tissue samples as compared with control samples treated with radiation alone.ConclusionPreoperative intratumoral TVEC with concurrent EBRT for locally advanced STS is safe and well-tolerated. This combination treatment may enhance immune responses in some cases but did not increase the proposed rate of pathological necrosis. The Caspase-3 biomarker may be associated with a positive effect of TVEC in sarcoma tumor tissue and should be explored in future studies.Trial registration numberNCT02453191.
Missing data in randomised controlled trials of rheumatoid arthritis drug therapy are substantial and handled inappropriately
Authors: Khan Nasim A , Torralba Karina D , Aslam Fawad 
Published: July 2021

ObjectivesTo analyse the amount, reporting and handling of missing data, approach to intention-to-treat (ITT) principle application and sensitivity analysis utilisation in randomised clinical trials (RCTs) of rheumatoid arthritis (RA). To assess the trend in such reporting 10 years apart (2006 and 2016).MethodsParallel group drug therapy RA RCTs with a clinical primary endpoint.Results176 studies enrolling a median of 160 (IQR 62–339) patients were eligible. In terms of actual analysis: 81 (46%) RCTs conducted ITT, 42 (23.9%) conducted modified ITT while 53 (30.1%) conducted non-ITT analysis. Only 58 of 97 (59.8%) RCTs reporting an ITT analysis actually performed it. The median (IQR) numbers of participants completing the trial and included in analysis for primary outcome were 86% (74%–91%) and 100% (97.1%–100%), respectively. 53 (32.7%) and 65 (40.1%) RCTs had >20% and 10%–20% missing primary outcome data, respectively. Missing data handling was unreported by 58 of 171 (33.9%) RCTs. When reported, vast majority used simple imputation methods. No significant trend towards improved reporting was seen between 2006 and 2016. Sensitivity analysis numerically improved from 2006 to 2016 (14.7% vs 21.4%).ConclusionsThere is significant discrepancy in the reported and the actual performed analysis in RA drug therapy RCTs. Nearly one-third of RCTs had >20% missing data. The reporting and methods of missing data handling remain inadequate with high usage of non-preferred simple imputation methods. Sensitivity analysis utilisation was low. No trend towards better missing data reporting and handling was seen.
Responses to pictorial versus text-only cigarillo warnings among a nationally representative sample of US young adults
Authors: Cornacchione Ross Jennifer , Lazard Allison J , King Jessica L , Noar Seth M , Reboussin Beth A , Jenson Desmond , Sutfin Erin L 
Published: July 2021

BackgroundThe US Food and Drug Administration requires six text-only warnings for cigar products, including cigarillos. Research has demonstrated the superiority of pictorial over text-only cigarette warnings, yet the relative effectiveness of pictorial warnings for cigarillos has not been examined. We examined the impact of pictorial cigarillo warnings compared with text-only warnings.MethodsData were collected from a nationally representative sample of US young adult (18–29) cigarillo users and susceptible non-users. Participants were randomised to one of three experimental conditions: text-only or one of two pictorial conditions (combined for analyses). For each warning, we assessed negative emotional reactions, cognitive elaboration (ie, thinking about cigarillo risks) and perceived message effectiveness (PME).ResultsParticipants (N=661) were 46.5% female, 64.7% white and 21.9% Hispanic; 34.1% reported past 30-day cigarillo use; 41.4% were lifetime users (excluding past 30-day use); and 24.4% were susceptible non-users. Pictorial warnings elicited more negative emotional reactions and higher PME than text-only warnings (p values<0.01), with interactions showing the largest effects for past 30-day users (emotional reactions: d=0.99, PME: d=0.63). For cognitive elaboration, there was no main effect of warning type, but an interaction revealed effects for past 30-day users (p<0.05, d=0.46).ConclusionsPictorial cigarillo warnings elicited greater negative emotional reactions and PME compared with text-only warnings. These effects and the effects on cognitive elaboration were strongest for past 30-day users. Our findings extend research on cigarette warnings to cigarillos, demonstrating that pictorial warnings are superior to text-only warnings for cigarillos in eliciting beneficial responses.
On Pythagorean Triples and the Primitive Roots Modulo a Prime
Authors: Wang Jingzhe 
Published: July 2021

In this paper, we use the elementary methods and the estimates for character sums to study a problem related to primitive roots and the Pythagorean triples and prove the following result: let

p

be an odd prime large enough. Then, there must exist three primitive roots

x
,

y

, and

z

modulo

p

such that

x

2

+

y

2

=

z

2

.
Association Between Hospital Volumes and Clinical Outcomes for Patients With Nontraumatic Subarachnoid Hemorrhage
Authors: Leifer Dana , Fonarow Gregg C. , Hellkamp Anne , Baker David , Hoh Brian L. , Prabhakaran Shyam , Schoeberl Mark , Suter Robert , Washington Chad , Williams Scott , Xian Ying , Schwamm Lee H. 
Published: July 2021

Background
Previous studies of patients with nontraumatic subarachnoid hemorrhage (SAH) suggest better outcomes at hospitals with higher case and procedural volumes, but the shape of the volume‐outcome curve has not been defined. We sought to establish minimum volume criteria for SAH and aneurysm obliteration procedures that could be used for comprehensive stroke center certification.

Methods and Results

Data from 8512 discharges in the National Inpatient Sample (NIS) from 2010 to 2011 were analyzed using logistic regression models to evaluate the association between clinical outcomes (in‐hospital mortality and the NIS‐SAH Outcome Measure [NIS‐SOM]) and measures of hospital annual case volume (nontraumatic SAH discharges, coiling, and clipping procedures). Sensitivity and specificity analyses for the association of desirable outcomes with different volume thresholds were performed. During 8512 SAH hospitalizations, 28.7% of cases underwent clipping and 20.1% underwent coiling with rates of 21.2% for in‐hospital mortality and 38.6% for poor outcome on the NIS‐SOM. The mean (range) of SAH, coiling, and clipping annual case volumes were 30.9 (1–195), 8.7 (0–94), and 6.1 (0–69), respectively. Logistic regression demonstrated improved outcomes with increasing annual case volumes of SAH discharges and procedures for aneurysm obliteration, with attenuation of the benefit beyond 35 SAH cases/year. Analysis of sensitivity and specificity using different volume thresholds confirmed these results. Analysis of previously proposed volume thresholds, including those utilized as minimum standards for comprehensive stroke center certification, showed that hospitals with more than 35 SAH cases annually had consistently superior outcomes compared with hospitals with fewer cases, although some hospitals below this threshold had similar outcomes. The adjusted odds ratio demonstrating lower risk of poor outcomes with SAH annual case volume ≥35 compared with 20 to 34 was 0.82 for the NIS‐SOM (95% CI, 0.71–094;
P
=0.0054) and 0.80 (95% CI, 0.68–0.93;
P
=0.0055) for in‐hospital mortality.

Conclusions
Outcomes for patients with SAH improve with increasing hospital case volumes and procedure volumes, with consistently better outcomes for hospitals with more than 35 SAH cases per year.
Association Between Age‐Related Macular Degeneration and Risk of Heart Failure: A Population‐Based Nested Case‐Control Study
Authors: Chang Chao‐Chien , Huang Chi‐Hung , Chou Yu‐Ching , Chang Jin‐Yin , Sun Chien‐An 
Published: July 2021

Background
Heart failure (HF) is a major health problem worldwide because of its high morbidity and mortality. Recently, the role of the microvasculature in HF has gained more attention. Age‐related macular degeneration (AMD) is manifested through geographic atrophy or the development of neovascularization. However, there are limited data on investigations about the association between AMD and HF. The purpose of this study was to examine the association of AMD with the risk of HF in a large population‐based cohort of men and women.

Methods and Results

A nested case‐control study using Taiwan’s National Health Insurance Research Database was conducted between 2000 and 2012. Newly diagnosed heart failure cases (n=13 721) and matched controls (n=54 884) in the database were recruited. Patients who had ≥2 clinical visits with a diagnosis of AMD at least 1 year before the diagnosis of HF were identified as patients with AMD. Conditional logistic regressions were performed to calculate odds ratios and 95% CIs to assess the association between AMD and risk of HF. AMD was associated with a 1.58‐fold increased risk of HF (95% CI, 1.16–1.87) (
P
<0.001) after adjustment for potential confounders. This significant association was evident in both nonexudative and exudative AMD subgroups.

Conclusions
Our study provides evidence that AMD was associated with an increased risk of HF. Further molecular and pathophysiological studies are needed to clarify the underlying pathophysiological mechanisms behind the association of AMD with HF.
Multiple Blood Biomarkers and Stroke Risk in Atrial Fibrillation: The REGARDS Study
Authors: Singleton Matthew J. , Yuan Ya , Dawood Farah Z. , Howard George , Judd Suzanne E. , Zakai Neil A. , Howard Virginia J. , Herrington David M. , Soliman Elsayed Z. , Cushman Mary 
Published: July 2021

Background
Atrial fibrillation is associated with increased stroke risk; available risk prediction tools have modest accuracy. We hypothesized that circulating stroke risk biomarkers may improve stroke risk prediction in atrial fibrillation.

Methods and Results

The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort study of 30 239 Black and White adults age ≥45 years. A nested study of stroke cases and a random sample of the cohort included 175 participants (63% women, 37% Black adults) with baseline atrial fibrillation and available blood biomarker data. There were 81 ischemic strokes over 5.2 years in these participants. Adjusted for demographics, stroke risk factors, and warfarin use, the following biomarkers were associated with stroke risk (hazard ratio [HR]; 95% CI for upper versus lower tertile): cystatin C (3.16; 1.04–9.58), factor VIII antigen (2.77; 1.03–7.48), interleukin‐6 (9.35; 1.95–44.78), and NT‐proBNP (N‐terminal B‐type natriuretic peptide) (4.21; 1.24–14.29). A multimarker risk score based on the number of blood biomarkers in the highest tertile was developed; adjusted HRs of stroke for 1, 2, and 3+ elevated blood biomarkers, compared with none, were 1.75 (0.57–5.40), 4.97 (1.20–20.5), and 9.51 (2.22–40.8), respectively. Incorporating the multimarker risk score to the CHA
2
DS
2
VASc score resulted in a net reclassification improvement of 0.34 (95% CI, 0.04–0.65).

Conclusions
Findings in this biracial cohort suggested the possibility of substantial improvement in stroke risk prediction in atrial fibrillation using blood biomarkers or a multimarker risk score.
Risk Factors and Clinical Outcomes of Nonhome Discharge in Patients With Acute Decompensated Heart Failure: An Observational Study
Authors: Washida Koichi , Kato Takao , Ozasa Neiko , Morimoto Takeshi , Yaku Hidenori , Inuzuka Yasutaka , Tamaki Yodo , Seko Yuta , Yamamoto Erika , Yoshikawa Yusuke , Kitai Takeshi , Yamashita Yugo , Iguchi Moritake , Nagao Kazuya , Kawase Yuichi , Morinaga Takashi , Toyofuku Mamoru , Furukawa Yutaka , Ando Kenji , Kadota Kazushige , Sato Yukihito , Kuwahara Koichiro , Kimura Takeshi 
Published: July 2021

Background
No clinical studies have focused on the factors associated with discharge destination in patients with acute decompensated heart failure.

Methods and Results

Of 4056 consecutive patients hospitalized for acute decompensated heart failure in the KCHF (Kyoto Congestive Heart Failure) registry, we analyzed 3460 patients hospitalized from their homes and discharged alive. There were 3009 and 451 patients who were discharged to home and nonhome, respectively. We investigated the factors associated with nonhome discharge and compared the outcomes between home discharge and nonhome discharge. Factors independently and positively associated with nonhome discharge were age ≥80 years (odds ratio [OR],1.76; 95% CI,1.28–2.42), body mass index ≤22 kg/m
2
(OR,1.49; 95% CI,1.12–1.97), poor medication adherence (OR, 2.08; 95% CI,1.49–2.88), worsening heart failure (OR, 2.02; 95% CI, 1.46–2.82), stroke during hospitalization (OR, 3.74; 95% CI, 1.75–8.00), functional decline (OR, 12.24; 95% CI, 8.74–17.14), and length of hospital stay >16 days (OR, 4.14; 95% CI, 3.01–5.69), while those negatively associated were diabetes mellitus (OR, 0.69; 95% CI, 0.51–0.94), cohabitants (OR, 0.62; 95% CI, 0.46–0.85), and ambulatory state before admission (OR, 0.25; 95% CI, 0.18–0.36). The cumulative 1‐year incidence of all‐cause death was significantly higher in the nonhome discharge group than in the home discharge group. The nonhome discharge group compared with the nonhome discharge group was associated with a higher adjusted risk for all‐cause death (hazard ratio, 1.66;
P
<0.001).

Conclusions
The discharge destination of patients with acute decompensated heart failure is influenced by factors such as prehospital social background, age, body mass index, low self‐care ability, events during hospitalization (worsening heart failure, stroke, etc), functional decline, and length of hospital stay; moreover, the prognosis of nonhome discharge patients is worse than that of home discharge patients.

Registration Information
clinicaltrials.gov. Identifier: NCT02334891.