Effect of Dapagliflozin, Compared With Placebo, According to Baseline Risk in DAPA-HF

Abstract Background US and European guidelines diverge on whether to vaccinate adults who are not at high risk for cardiovascular events against influenza. Here, we investigated the associations between influenza vaccination and risk for acute myocardial infarction, stroke and pulmonary embolism during the 2009 pandemic in Norway, when vaccination was recommended to all adults. Methods Using national registers, we studied all vaccinated Norwegian individuals who suffered AMI, stroke, or pulmonary embolism from May 1, 2009 through September 30, 2010. We defined higher-risk individuals as those using anti-diabetic, anti-obesity, anti-thrombotic, pulmonary or cardiovascular medications (i.e. individuals to whom vaccination was routinely recommended); all other individuals were regarded as having lower-risk. We estimated incidence rate ratios with 95% CI using conditional Poisson regression in the pre-defined risk periods up to 180 days following vaccination compared to an unexposed time-period, with adjustment for season or daily temperature. Results Overall, we observed lower risk for cardiovascular events following influenza vaccination. When stratified by baseline risk, we observed lower risk across all three outcomes in association with vaccination among higher-risk individuals. In this subgroup, relative risks were 0.72 (0.59–0.88) for AMI, 0.77 (0.59–0.99) for stroke, and 0.73 (0.45–1.19) for pulmonary embolism in the period 1–14 days following vaccination when compared to the background period. These associations remained essentially the same up to 180 days after vaccination. In contrast, the corresponding relative risks among subjects not using medications were 4.19 (2.69–6.52), 1.73 (0.91–3.31) and 2.35 (0.78–7.06). Conclusion In this nationwide study, influenza vaccination was associated with overall cardiovascular benefit. This benefit was concentrated among those at higher cardiovascular risk as defined by medication use. In contrast, our results demonstrate no comparable inverse association with thrombosis-related cardiovascular events following vaccination among those free of cardiovascular medications at baseline. These results may inform the risk–benefit balance for universal influenza vaccination.

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Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

Nature Reviews Nephrology ◽

10.1038/s41581-021-00418-2 ◽

2021 ◽

Author(s):

John R. Prowle ◽

Lui G. Forni ◽

Max Bell ◽

Michelle S. Chew ◽

Mark Edwards ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Kidney Disease ◽

Kidney Injury ◽

Adverse Outcomes ◽

Baseline Risk ◽

Major Surgery ◽

Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

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Real World Performance Evaluation of Transcatheter Aortic Valve Implantation

Journal of Clinical Medicine ◽

10.3390/jcm10091890 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1890

Author(s):

Gabriele Pesarini ◽

Gabriele Venturi ◽

Domenico Tavella ◽

Leonardo Gottin ◽

Mattia Lunardi ◽

...

Keyword(s):

Aortic Valve ◽

Real World ◽

Baseline Risk ◽

Risk Scores ◽

World Population ◽

Control Analysis ◽

Transcatheter Aortic Valve ◽

Procedural Control ◽

Risk Patients ◽

Over Time

Background: The aim of this research is to describe the performance over time of transcatheter aortic valve implantations (TAVIs) in a high-volume center with a contemporary, real-world population. Methods: Patients referred for TAVIs at the University Hospital of Verona were prospectively enrolled. By cumulative sum failures analysis (CUSUM), procedural-control curves for standardized combined endpoints—as defined by the Valve Academic Research Consortium-2 (VARC-2)—were calculated and analyzed over time. Acceptable and unacceptable limits were derived from recent studies on TAVI in intermediate and low-risk patients to fit the higher required standards for current indications. Results: A total of 910 patients were included. Baseline risk scores significantly reduced over time. Complete procedural control was obtained after approximately 125 and 190 cases for device success and early safety standardized combined endpoints, respectively. High risk patients (STS ≥ 8) had poorer outcomes, especially in terms of VARC-2 clinical efficacy, and required a higher case load to maintain in-control and proficient procedures. Clinically relevant single endpoints were all influenced by operator’s experience as well. Conclusions: Quality-control analysis for contemporary TAVI interventions based on standardized endpoints suggests the need for relevant operator’s experience to achieve and maintain optimal clinical results, especially in higher-risk subjects.

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Rituximab-Containing Risk-Adapted Treatment Strategy in Nodular Lymphocyte Predominant Hodgkin Lymphoma: 7-Years Follow-Up

Cancers ◽

10.3390/cancers13081760 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1760

Author(s):

Novella Pugliese ◽

Marco Picardi ◽

Roberta Della Pepa ◽

Claudia Giordano ◽

Francesco Muriano ◽

...

Keyword(s):

Side Effects ◽

Hodgkin Lymphoma ◽

Prognostic Score ◽

Single Agent ◽

Response To Therapy ◽

Baseline Risk ◽

Historical Cohort ◽

Treatment Groups

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.

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Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity

BMJ Open ◽

10.1136/bmjopen-2020-045572 ◽

2021 ◽

Vol 11 (8) ◽

pp. e045572

Author(s):

Andreas Daniel Meid ◽

Ana Isabel Gonzalez-Gonzalez ◽

Truc Sophia Dinh ◽

Jeanet Blom ◽

Marjan van den Akker ◽

...

Keyword(s):

Prognostic Model ◽

Prediction Models ◽

Hospital Admissions ◽

Absolute Risk ◽

External Validation ◽

Baseline Risk ◽

Study Heterogeneity ◽

Related Quality ◽

Individual Participant ◽

Risk Predictor

ObjectiveTo explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients.Study design and settingUsing individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV).ResultsPrior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions.ConclusionsPredictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully.Trial registration numberPROSPERO id: CRD42018088129.

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Testing for non-inferior mortality: a systematic review of non-inferiority margin sizes and trial characteristics

BMJ Open ◽

10.1136/bmjopen-2020-044480 ◽

2021 ◽

Vol 11 (4) ◽

pp. e044480

Author(s):

Sandra Pong ◽

Martin Urner ◽

Robert A Fowler ◽

Nicholas Mitsakakis ◽

Winnie Seto ◽

...

Keyword(s):

Systematic Review ◽

Primary Outcome ◽

Absolute Risk ◽

Methodological Issue ◽

Medical Specialty ◽

Risk Difference ◽

Baseline Risk ◽

Industry Funding ◽

Eligibility Criteria ◽

Randomised Controlled

ObjectiveTo describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size.DesignSystematic review.Data sourcesMedline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019.Eligibility criteriaProspective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention.Results3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%–10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3–1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size.ConclusionAbsolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.

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P009 Service evaluation to optimise ophthalmological services for hydroxychloroquine retinal screening

Rheumatology ◽

10.1093/rheumatology/keab247.008 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Chan Ning Lee ◽

Mrinalini Dey ◽

Mooikhin Hng ◽

Simon Peterson ◽

Imna Rahiman ◽

...

Keyword(s):

Patient Education ◽

Service Evaluation ◽

Continuous Treatment ◽

Fundus Photography ◽

Baseline Risk ◽

Service Development ◽

Cross Sectional ◽

Retinal Pathology ◽

Retinal Screening ◽

Sd Oct

Abstract Background/Aims Hydroxychloroquine (HCQ), a frequently-used therapy in rheumatology, can be associated with retinal toxicity. More stringent screening and monitoring guidelines for HCQ-related retinopathy were published by the Royal College of Ophthalmologists (RCOphth) in 2018. Recommendations include: 1) baseline retinal screening within six-twelve months of commencing HCQ; 2) subsequent annual monitoring for at-risk patients, specifically: concurrent tamoxifen-use, estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, HCQ dose >5mg/kg/day; 3) annual monitoring for all other patients after five years continuous treatment; 4) patient education on HCQ retinopathy. We quantified the rheumatology HCQ exposure and estimated burden on ophthalmology, to inform the development of HCQ retinal screening services. Methods Cross-sectional data were extracted for patients established on HCQ between 1995-2020 including: weight; eGFR; concomitant retino-toxic medication; concomitant retinal pathology; HCQ dose and duration; documentation of patient education on retinal side-effects. Documentation of relevant ophthalmic testing at baseline (i.e. at time of starting HCQ) were recorded, specifically colour fundus photography, spectral domain optical coherence tomography (SD-OCT) and 10-2 Humphrey visual field (HVF) testing as necessary. Subsequent monitoring with 10-2 HVFs, SD-OCT, autofluorescence (AF) and electrodiagnostic tests (EDTs) as appropriate annually from baseline and from 5 years was recorded. Results 150 patients were included, 84% female, with a mean baseline age of 50.7 years (SD 14.8) and mean weight of 76.4kg (SD 17.6). 63% were on HCQ >5 years (mean duration 7.0 years, SD 5.1). At time of auditing, 50% (75/150) patients had permanently ceased HCQ (62% due to treatment >5 years). 60% patients had documented evidence of education regarding HCQ retinopathy. Of the 150 patients, 39% had baseline risks for retinopathy. 6% had a baseline eGFR <60ml/min/1.73m2. 32% were commenced on HCQ dose greater than 5mg/kg/day. No patients were on concomitant tamoxifen; one patient was on a known retino-toxic drug (quinine). 4% of patients had pre-existing retinal pathology. Of the 75 patients still taking HCQ at time of auditing, 27 (36%) had baseline risk factors warranting yearly retinal screening and 44 (58%) had been on treatment >5years. Most ophthalmology reviews were put on hold until a screening service was established. Of the small number (5.3%) that had baseline ophthalmic screening, 12.5% had colour photography and 75% had SD-OCT. No patients required HVF testing or EDTs. Annual screening revealed 50% of patients had 10-2 HVFs; 75% had SD-OCT; 75% had AF. Only one patient developed maculopathy, not attributed to HCQ. Conclusion Our results demonstrate the need for service development to facilitate adherence to RCOphth guidance. Up to 40% of patients started on HCQ have baseline risks for retinopathy, most due to dosing >5mg/kg/day warranting yearly screening. Our findings will inform development of a rheumatology HCQ retinal screening pathway and services, to ensure safe long-term use of HCQ. Disclosure C. Lee*: None. M. Dey*: None. M. Hng: None. S. Peterson: None. I. Rahiman: None. M. Elshafei: None. C. Estrach: None. N.J. Goodson: None.

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Longitudinal courses of suicidal ideation in U.S. military veterans: a 7-year population-based, prospective cohort study

Psychological Medicine ◽

10.1017/s0033291721000301 ◽

2021 ◽

pp. 1-10

Author(s):

Sarah Herzog ◽

Jack Tsai ◽

Brandon Nichter ◽

Lorig Kachadourian ◽

Ilan Harpaz-Rotem ◽

...

Keyword(s):

Suicidal Ideation ◽

Protective Factors ◽

Physical Health ◽

Social Connectedness ◽

Risk And Protective Factors ◽

Population Based ◽

Baseline Risk ◽

Relative Risk Ratio ◽

National Probability Sample ◽

New Onset

Abstract Background Varied longitudinal courses of suicidal ideation (SI) may be linked to unique sets of risk and protective factors. Method A national probability sample of 2291 U.S. veterans was followed over four assessments spanning 7 years to examine how a broad range of baseline risk and protective factors predict varying courses of SI. Results Most veterans (82.6%) denied SI at baseline and all follow-ups, while 8.7% had new onset SI, 5.4% chronic SI, and 3.3% remitted SI. Compared to the no-SI group, chronic SI was associated with childhood trauma, baseline major depressive and/or posttraumatic stress disorder (MDD/PTSD), physical health difficulties, and recent traumatic stressors. Remitted veterans had the highest risk of a prior suicide attempt (SA) compared to no-SI [relative risk ratio (RRR) = 3.31] and chronic SI groups (RRR = 4.65); and high rates of MDD/PTSD (RRR = 7.62). New onset SI was associated with recent stressors and physical health difficulties. All symptomatic SI groups reported decrements in protective factors, specifically, social connectedness, trait curiosity/exploration, and purpose in life. Conclusion Nearly one-in-five veterans reported SI over a 7-year period, most of whom evidenced new onset or remitted SI courses. Chronic and remitted SI may represent particularly high-risk SI courses; the former was associated with higher rates of prospective SA, and psychiatric and physical distress, and the latter with increased likelihood of prior SA, and isolation from social and mental health supports. Physical disability, MDD/PTSD, and recent stressors may be important precipitating or maintaining factors of SI, while social connectedness may be a key target for suicide prevention efforts.

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