Background
When the treatment effect on the outcome of interest is influenced by a baseline/demographic factor, investigators say that an interaction is present. In randomized clinical trials (RCTs), ...this type of analysis is typically referred to as subgroup analysis. Although interaction (or subgroup) analyses are usually stated as a secondary study objective, it is not uncommon that these results lead to changes in treatment protocols or even modify public health policies. Nonetheless, recent reviews have indicated that their proper assessment, interpretation and reporting remain challenging.
Results
Therefore, this article provides an overview of these challenges, to help investigators find the best strategy for application of interaction analyses on binary outcomes in RCTs. Specifically, we discuss the key points of formal interaction testing, including the estimation of both additive and multiplicative interaction effects. We also provide recommendations that, if adhered to, could increase the clarity and the completeness of reports of RCTs.
Conclusion
Altogether, this article provides a brief non‐statistical guide for clinical investigators on how to perform, interpret and report interaction (subgroup) analyses in RCTs.
Purpose
Acute kidney injury
(
AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed ...to determine their predictive properties for postoperative AKI severity within 30 days after HTx.
Methods
From 1984 to 2016, all consecutive HTx recipients (
n
= 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC).
Results
Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg,
p
trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47,
p
trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31,
p
trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02–1.32),
p
= 0.029; of PAPi 0.85 (0.75–0.96),
p
= 0.008. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models’ predictive accuracy.
Conclusions
Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors.
We aimed to systematically analyze the literature on the use of transcatheter aortic valve replacement (TAVR) to treat active aortic valve infective endocarditis (AV-IE). Surgery is declined in ...one-third of patients with IE who meet indications because of prohibitive surgical risk. TAVR might be an alternative for selected patients with AV-IE as a bridge-to-surgery or stand-alone therapy. PubMed/MEDLINE, Embase, and Cochrane databases were searched (2002–2022) for studies on TAVR use in active AV-IE. Of 450 identified reports, six met inclusion criteria (all men, mean age 71 ± 12 years, median Society of Thoracic Surgeons (STS) score 27, EuroSCORE 56). All patients were prohibitive surgical risk candidates. Five out of six patients had severe, and one patient had moderate aortic regurgitation on presentation. Five out of six patients had prosthetic valve endocarditis after surgical valve replacement 13 years before (median), and one patient had TAVR a year before hospitalization. All patients had cardiogenic shock as the indication for TAVR. Four patients received balloon-expanding, and two patients received self-expanding TAVR after a median of 19 (IQR 9–25) days from diagnosis of IE. No death or myocardial infarction occurred, but one patient had a stroke within the first 30 days. The median event-free time was 9 (IQR 6–14) months including no death, reinfection, relapse IE, or valve-related rehospitalization. Our review suggests that TAVR can be considered as an adjuvant therapy to medical treatment for selected patients in whom surgery is indicated for treatment of acute heart failure due to aortic valve destruction and incompetence caused by infective endocarditis, but who have a prohibitive surgical risk. Nonetheless, a well-designed prospective registry is urgently needed to investigate the outcomes of TAVR for this off-label indication. No evidence exists for using the TAVR to treat infection-related surgical indications such as uncontrolled infection or control of septic embolization.
Objectives Parkes Weber syndrome is a congenital vascular malformation which consists of capillary malformation, venous malformation, lymphatic malformation, and arteriovenous malformation. Although ...Parkes Weber syndrome is a clinically distinctive entity with serious complications, it is still frequently misdiagnosed as Klippel-Trenaunay syndrome that consists of the triad capillary malformation, venous malformation, and lymphatic malformation. Methods We performed a systematic review investigating clinical, diagnostic, and treatment modalities of Parkes Weber syndrome (PubMed/MEDLINE, Embase, and Cochrane databases). Thirty-six publications (48 patients) fulfilled the eligibility criteria. Results The median age of patients was 23 years (IQR, 8-32), and 24 (50.0%) were males. Lower extremity was affected in 42 (87.5%) and upper extremity in 6 (12.5%) patients; 15 (31.3%) patients developed high-output heart failure; 12 (25.0%) patients had chronic venous ulcerations, whereas 4 (8.3%) manifested distal arterial ischemia. The spinal arteriovenous malformations were reported in six (12.5%) patients and coexistence of aneurysmatic disease in five (10.4%) patients. The most frequently utilized invasive treatments were embotherapy followed by amputation and surgical arteriovenous malformation resection, and occasionally stent-graft implantation. All modalities showed clinical improvement. However, long follow-up and outcome remained unclear. Conclusion A diagnosis of Parkes Weber syndrome should be made on the presence of capillary malformation, venous malformation, lymphatic malformation, and arteriovenous malformation (as main defect) in overgrowth extremity. Arteriovenous malformation presents the criterion for distinguishing Parkes Weber syndrome from Klippel-Trenaunay syndrome, which is substantial for treatment strategy. The primary management goal should be patient's quality of life improvement and complication reduction. Embolization alone/combined with surgical resection targeting occlusion or removal of arteriovenous malformation "nidus" reliably leads to clinical improvement.
Background Remodeling biomarkers carry high potential for predicting adverse events in chronic heart failure ( CHF ) patients. However, temporal patterns during the course of CHF , and especially the ...trajectory before an adverse event, are unknown. We studied the prognostic value of temporal patterns of 14 cardiac remodeling biomarker candidates in stable patients with CHF from the Bio‐SHiFT (Serial Biomarker Measurements and New Echocardiographic Techniques in Chronic Heart Failure Patients Result in Tailored Prediction of Prognosis) study. Methods and Results In 263 CHF patients, we performed trimonthly blood sampling during a median follow‐up of 2.2 years. For the analysis, we selected all baseline samples, the 2 samples closest to the primary end point ( PE ), or the last sample available for end point–free patients. Thus, in 567 samples, we measured suppression of tumorigenicity‐2, galectin‐3, galectin‐4, growth differentiation factor‐15, matrix metalloproteinase‐2, 3, and 9, tissue inhibitor metalloproteinase‐4, perlecan, aminopeptidase‐N, caspase‐3, cathepsin‐D, cathepsin‐Z, and cystatin‐B. The PE was a composite of cardiovascular mortality, heart transplantation, left ventricular assist device implantation, and HF hospitalization. Associations between repeatedly measured biomarker candidates and the PE were investigated by joint modeling. Median age was 68 (interquartile range: 59–76) years with 72% men; 70 patients reached the PE . Repeatedly measured suppression of tumorigenicity‐2, galectin‐3, galectin‐4, growth differentiation factor‐15, matrix metalloproteinase‐2 and 9, tissue inhibitor metalloproteinase‐4, perlecan, cathepsin‐D, and cystatin‐B levels were significantly associated with the PE , and increased as the PE approached. The slopes of biomarker trajectories were also predictors of clinical outcome, independent of their absolute level. Associations persisted after adjustment for clinical characteristics and pharmacological treatment. Suppression of tumorigenicity‐2 was the strongest predictor (hazard ratio: 7.55 per SD difference, 95% CI : 5.53–10.30), followed by growth differentiation factor‐15 (4.06, 2.98–5.54) and matrix metalloproteinase‐2 (3.59, 2.55–5.05). Conclusions Temporal patterns of remodeling biomarker candidates predict adverse clinical outcomes in CHF . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01851538.
Renal dysfunction and anaemia are common in patients with acute heart failure (HF). It is not known whether their combined presence has additive prognostic value. We investigated their prognostic ...value separately and in combination, on prognosis in acute HF patients. Furthermore, we examined whether the improvement in prognosis was comparable between patients with and without renal dysfunction.
This prospective registry includes 1783 patients admitted to the (Intensive) Coronary Care Unit for acute HF in the period of 1985-2008. The outcome measure was the composite of all-cause mortality, heart transplantation and left ventricular assist device implantation. In patients without renal dysfunction, anemia was associated with worse 30-day outcome (HR 2.91; 95% CI 1.69-5.00), but not with 10-year outcome (HR 1.13 95% CI 0.93-1.37). On the contrary, anemia was found to influence prognosis in patients with renal dysfunction, both at 30 days (HR 1.93 95% CI 1.33-2.80) and at 10 years (HR 1.27 95% CI 1.10-1.47). Over time, the 10-year survival rate improved in patients with preserved renal function (HR 0.73 95% CI 0.55-0.97), but not in patients with renal dysfunction.
The long-term prognosis of acute HF patients with a preserved renal function was found to have improved significantly. However, the prognosis of patients with renal dysfunction did not change. Anemia was a strong prognosticator for short-term outcome in all patients. In patients with renal dysfunction, anemia was also associated with impaired long-term prognosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a case of polymicrobial sepsis with Capnocytophaga spp. complicated by purpura fulminans following a dog-bite in a 50-year-old-man with an extensive history of opioid use disorder. ...Generally, severe Capnocytophaga cases are thought to occur in patients with underlying immune deficiencies. However, this case highlights the importance of maintaining clinical suspicion for Capnocytophaga infection in immunocompetent patients, and we discuss the role of chronic opioid-use in severe infection.
•Polymicrobial sepsis with Capnocytophaga in immunocompetent 50-year-old man.•Chronic opioid use and its potential role in severe Capnocytophaga infection.•Purpura fulminans can be an early indication of severe Capnocytophaga infection.
Background
It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes.
Hypothesis
...Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.
Methods
During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N‐acetyl‐β‐d‐glucosaminidase (NAG), and kidney‐injury‐molecule (KIM)‐1. The degree of tubular injury was ranked according to NAG and KIM‐1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF‐hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation.
Results
Higher baseline NT‐proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR 95%CI, 95% confidence interval per doubling NT‐proBNP: 1.26 1.07‐1.49; per 10 mL/min/1.73 m2 eGFR decrease 1.16 1.03‐1.31). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 1.08‐1.62; spironolactone per 25 mg decrease: 1.76 1.07‐2.89; per 10 mL/min/1.73 m2 eGFR increase: 1.40 1.20‐1.63). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR 95%CI: WRF 1.9 1.1‐3.4, tubular 8.4 2.6‐27.9; when combined risk was highest 15.0 2.0‐111.0).
Conclusion
Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.
Abstract only Introduction: Left atrial appendage (LAA) thrombus increases thromboembolic risk in patients with atrial fibrillation (AF). Importantly, 40% of LAA thrombus patients will have an ...inadequate response to anticoagulation during follow-up. Of note, these patients are frequently followed by medicine residents in the clinic. Therefore, we aimed to explore residents' knowledge on anticoagulation use for the treatment of LAA thrombus. Hypothesis: Insufficient knowledge on anticoagulation for the treatment of LAA thrombus could contribute to inadequate treatment response during patients' follow-up. Methods: All medicine residents (n=96) at Rutgers University New Jersey Medical School were emailed a 26-question survey on the indication, dosing, pharmacokinetics and clinical experience using direct oral anticoagulants (DOACs) and vitamin-K-antagonists (VKA) in AF patients with LAA thrombus. Results: Of 62 responders, 42 (68%) have been prescribing DOACs in the clinic with apixaban being most commonly prescribed. Thirty-seven (61%) indicated DOACs as the first-line agents for LAA thrombus whereas 24 (39%) chose VKA. Nineteen (33%) responders indicated apixaban dosing correctly, and 51 (84%) indicated appropriately relation of apixaban with meals. If follow-up imaging reconfirmed LAA thrombus, 54 (89%) would switch to VKA whereas 7 (11%) would use other DOACs. Nineteen (32%) responders indicated rivaroxaban dosing correctly and only 10 (16%) indicated appropriately how to administer rivaroxaban with meals. If follow-up imaging reconfirmed LAA thrombus, 43 (71%) would switch to VKA whereas 18 (29%) would use other DOACs. Forty-one (72%) responders indicated dabigatran dosing correctly and 36 (58%) indicated no relation to food intake. If follow-up imaging reconfirmed LAA thrombus, 40 (65%) responders would switch to VKA whereas 22 (35%) would use other DOACs. For VKA, 51 (88%) indicated therapeutic INR range of 2-3 and 7 (12%) chose 2.5-3.5. If follow-up imaging reconfirmed LAA thrombus, 38 (61%) would increase INR goal whereas 24 (39%) would switch to DOACs. Conclusions: This survey identified knowledge gaps in dosing and pharmacokinetics of DOACs among medicine residents despite being more likely to prescribe DOACs over VKA to treat LAA thrombus.
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