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  • Ovid Technologies (Wolters Kluwer Health)  (12)
  • 2020-2024  (12)
  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 148, No. 13 ( 2023-09-26), p. 1000-1010
    Abstract: The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are not well known but are needed to guide preventive strategies. METHODS: Patients with first-time TIA (index date) in the Danish Stroke Registry (January 2014–December 2020) were included and matched 1:4 with individuals from the background population and 1:1 with patients with a first-time ischemic stroke on the basis of age, sex, and calendar year. The incidences of ischemic stroke and mortality from index date were estimated by Aalen-Johansen and Kaplan-Meier estimators, respectively, and compared between groups using multivariable Cox regression. RESULTS: We included 21 500 patients with TIA, 86 000 patients from the background population, and 21 500 patients with ischemic stroke (median age, 70.8 years [25th–75th percentile, 60.8–78.7]; 53.1% males). Patients with TIA had more comorbidities than the background population, yet less than the control stroke population. The 5-year incidence of ischemic stroke after TIA (6.1% [95% CI, 5.7–6.5] ) was higher than the background population (1.5% [95% CI, 1.4–1.6], P 〈 0.01; hazard ratio, 5.14 [95% CI, 4.65–5.69]) but lower than the control stroke population (8.9% [95% CI, 8.4–9.4] , P 〈 0.01; hazard ratio, 0.58 [95% CI, 0.53–0.64]). The 5-year mortality for patients with TIA (18.6% [95% CI, 17.9–19.3] ) was higher than the background population (14.8% [95% CI, 14.5–15.1], P 〈 0.01; hazard ratio, 1.26 [95% CI, 1.20–1.32]) but lower than the control stroke population (30.1% [95% CI, 29.3–30.9] , P 〈 0.01; hazard ratio, 0.41 [95% CI, 0.39–0.44]). CONCLUSIONS: Patients with first-time TIA had an ischemic stroke incidence of 6.1% during the 5-year follow-up period. After adjustment for relevant comorbidities, this incidence was approximately 5-fold higher than what was found for controls in the background population and 40% lower than for patients with recurrent ischemic stroke.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1466401-X
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Applied Immunohistochemistry & Molecular Morphology Vol. 28, No. 9 ( 2020-10), p. 694-701
    In: Applied Immunohistochemistry & Molecular Morphology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 9 ( 2020-10), p. 694-701
    Abstract: The protein p57 is encoded by CDKN1C. This gene is known to be paternally imprinted and maternally expressed in cytotrophoblasts and villous stromal cells. We present a method for evaluating p57 antibodies (Abs) in hydatidiform mole (HM) and demonstrate the results for 4 p57 Abs in various cell types. Five cases of complete HM, diploid with 2 paternal genome sets (CHM;PP), 5 cases of partial HM, triploid with 2 paternal and 1 maternal genome sets (PHM;PPM), and 5 cases of non-HM, with diploid biparental genomes (non-HM;PM) were stained with p57 Abs: 57P06, EP183, KP10, and KP39. Assessment of the fraction of nuclei stained, and the intensity of staining of the nuclei and cytoplasm was performed. For evaluation of the Abs, the observations in cytotrophoblasts, villous stromal cells, maternal decidual cells, and intermediate trophoblasts were scored. The fraction of stained nuclei in cytotrophoblasts and villous stromal cells and the staining of cytoplasm showed to be important parameters in the evaluation of the Abs. 57P06 was evaluated as optimal. KP10 showed moderate cytoplasmatic staining in maternal decidual cells and intermediate trophoblasts, and was evaluated as good. EP183 was evaluated as poor, primarily due to nuclear staining in ≥10% of the villous stromal cells in CHM;PP. KP39 was evaluated as poor, primarily due to strong cytoplasmatic staining in some cytotrophoblasts and villous stromal cells. A structured testing of p57 for diagnosing HM is recommended. No nuclear staining was observed in syncytiotrophoblasts of CHM;PP, indicating that in syncytiotrophoblasts also, CDKN1C is paternally imprinted.
    Type of Medium: Online Resource
    ISSN: 1541-2016
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2052398-1
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  • 3
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 18 ( 2021-09-21)
    Abstract: Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new‐onset HFrEF treated with either carvedilol or metoprolol for all‐cause mortality until the end of 2018. Follow‐up started 120 days after initial HFrEF diagnosis to allow initiation of guideline‐directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well‐balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow‐up. We observed no mortality differences between carvedilol and metoprolol, multivariable‐adjusted hazard ratio (HR) 0.97 (0.90–1.05) in patients with T2D versus 1.00 (0.95–1.05) for those without T2D, P for difference =0.99. Rates of new‐onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75–0.91), P 〈 0.0001. Conclusions In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long‐term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new‐onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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  • 4
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Introduction: In EMPA-REG OUTCOME®, the sodium-glucose transporter inhibitor, empagliflozin (EMPA), reduced the risk of first cardiovascular (CV) events primarily CV mortality and hospitalization for heart failure in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease. In analyses including total events, EMPA also reduced the risk of myocardial infarction (MI). Here we report the effects of EMPA on the total number of MIs by subtype. Methods: Patients were randomized to receive EMPA 10 mg, EMPA 25 mg, or placebo. We assessed the effect of pooled EMPA versus placebo on total (first plus recurrent) events of fatal and non-fatal MI using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post-hoc, we analyzed established subtypes of MI: Type 1: Typically related to plaque-rupture or thrombus; Type 2: Supply-demand; Type 3: Sudden-death related (i.e., fatal MI); Type 4: Percutaneous coronary intervention related; and Type 5: Coronary artery bypass graft related. Except type 3 MIs, MIs were non-fatal. The MIs, including subtypes, were centrally adjudicated and could be assigned to more than one subtype. Results: 7,020 patients were treated. Overall, there was 421 total events of MIs. Specifically, 299, 86, 26, 19, and 1 of the MIs were classified as type 1, 2, 3, 4, and 5 MIs, respectively (not mutually exclusive). Overall, EMPA reduced the risk of total events of MI by 21% versus placebo (rate ratio [95% CI], EMPA versus placebo: 0.79 [0.620; 0.998] , p=0.0486; each MI only counted once). The overall reduction in total events of MIs by EMPA was driven by the effect on type 1 and 2 MIs, as well as type 3 MIs, with limited number of type 4 and 5 MIs (Figure). Conclusions: EMPA reduced the risk of total MI events with consistent effects across the most common etiologies, the type 1 (plaque-rupture or thrombus) and 2 (supply-demand) MIs.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1466401-X
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  • 5
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 14 ( 2020-07-21)
    Abstract: Mortality is increased following a hospitalization for decompensated heart failure ( HF ), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for HF . Methods and Results From nationwide administrative registers, we identified all Danish patients who were diagnosed with HF from 2001 to 2016 and received angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker and β blocker within 120 days. Subsequent follow‐up tracked progressive events of diuretic intensification and HF hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1‐year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened HF controls and absolute 1‐year mortality risks were calculated using Kaplan‐Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow‐up. One‐year mortality was 18.0% after an intensification event, 22.6% after HF hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1‐year death after an intensification event was 1.75 (95% CI , 1.66–1.85), and it was 2.28 (95% CI , 2.16–2.41) after HF hospitalization. Conclusions In a nationwide cohort of patients with HF , outpatient intensification events were associated with almost 2‐fold risk of mortality during the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2653953-6
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  • 6
    In: Pain, Ovid Technologies (Wolters Kluwer Health), Vol. 161, No. 12 ( 2020-12), p. 2731-2736
    Abstract: The presence and magnitude of placebo responses is important for the outcome in clinical trials of analgesics. This explorative study aimed at identifying patients and trial-specific factors with impact on this response in randomized, controlled, cross-over trials in peripheral neuropathic pain. Data were derived from 7 trials and included observations on pinprick hyperalgesia, allodynia, and pain on repetitive stimulation. The studies were all performed by the same collaboration group in Denmark. Pain was rated daily using numeric 0 to 10 point rating scales (NRS) and placebo response was calculated as the difference in weekly average or median numeric rating scale from baseline to the last week of treatment. A clinically meaningful placebo response was defined as more than 30% reduction of pain on placebo. In 318 individual observations, the response was on average small (0.17 points, range −4.5 to 6). There was no significant impact on size of placebo response of trial-specific factors such as treatment sequence and chance of having placebo treatment in each period or of the patient-specific factors age, sensory signs, and pain symptoms. The findings were similar in patients having placebo in the first treatment period. There was no marked difference between patients with (n = 43) and without (n = 275) a clinically meaningful placebo response with respect to the patient-specific factors including frequency of sensory signs and symptoms. In conclusion, this study on cross-over trials in peripheral neuropathic pain found no robust impact of trial and patient-specific factors on the placebo response.
    Type of Medium: Online Resource
    ISSN: 0304-3959 , 1872-6623
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1494115-6
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  • 7
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health)
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2428100-1
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  • 8
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 22 ( 2021-11-16)
    Abstract: It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first‐degree family members with HF or dilated cardiomyopathy (DCM). Methods and Results Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre‐existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first‐degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5‐year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8–10.7] versus 5.6% [95% CI, 5.0–6.1] ; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13–1.64] ). (HF 8.4% [95% CI, 7.0–9.8] versus 4.5% [95% CI, 4.1–5.0] ); (adjusted HR, 1.49 [95% CI, 1.22–1.82]). However, familial HF/DCM was not significantly associated with an increased 5‐year risk and rate of death (0.8% [95% CI, 0.4–1.2] versus 1.1% [95% CI, 0.8–1.3]); (adjusted HR, 0.80 [95% CI, 0.46–1.39] ). Conclusions In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first‐degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5‐year incidence of HF compared with those without.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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  • 9
    In: Circulation: Cardiovascular Quality and Outcomes, Ovid Technologies (Wolters Kluwer Health), Vol. 13, No. 7 ( 2020-07)
    Abstract: Heart failure (HF) in patients with type 2 diabetes mellitus (T2D) has received growing attention. We examined the effect of HF development on prognosis compared with other cardiovascular or renal diagnoses in patients with T2D. Methods and Results: Patients with new T2D diagnosis patients were identified between 1998 and 2015 through Danish nationwide registers. At yearly landmark timepoints after T2D diagnosis, we estimated the 5-year risks of death, 5-year risk ratios, and decrease in lifespan within 5 years associated with the development of HF, ischemic heart disease, stroke, peripheral artery disease, and chronic kidney disease. A total of 153 403 patients with newly diagnosed T2D were followed for a median of 9.7 years (interquartile range, 5.8–13.9) during which 48 087 patients died. The 5-year risk ratio of death associated with HF development 5 years after T2D diagnosis was 3 times higher (CI, 2.9–3.1) than patients free of diagnoses (CI, 2.9–3.1). Five-year risk ratios were lower for ischemic heart disease (1.3 [1.3–1.4]), stroke (2.2 [2.1–2.2] ), chronic kidney disease (1.7 [1.7–1.8]), and peripheral artery disease (2.3 [2.3–2.4] ). The corresponding decrease in lifespan within 5 years when compared with patients free of diagnoses (in months) was HF 11.7 (11.6–11.8), ischemic heart disease 1.6 (1.5–1.7), stroke 6.4 (6.3–6.5), chronic kidney disease 4.4 (4.3–4.6), and peripheral artery disease 6.9 (6.8–7.0). HF in combination with any other diagnosis imposed the greatest risk of death and decrease in life span compared with other combinations. Supplemental analysis led to similar results when stratified according to age, sex, and comorbidity status, and inclusion period. Conclusions: HF development, at any year since T2D diagnosis, was associated with the highest 5-year absolute and relative risk of death, and decrease in lifespan within 5 years, when compared with development of other cardiovascular or renal diagnoses.
    Type of Medium: Online Resource
    ISSN: 1941-7713 , 1941-7705
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2453882-6
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  • 10
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 6 ( 2022-03-15)
    Abstract: Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. Methods and Results Patients with atrial fibrillation on OAC therapy who had a first‐time ischemic stroke were identified in the Danish Stroke Registry (2005–2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio 〈 2 [subtherapeutic], international normalized ratio 2–3 [therapeutic] , international normalized ratio 〉 3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0–58 points), and the risk of very severe stroke (0–14 points) was analyzed by multivariable logistic regression. One‐year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%] , therapeutic [43%], supratherapeutic [11%] ), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%] , and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR] , 2.06 [95% CI, 1.28–3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60–2.57] ) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1‐year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29–2.13] ); HR, 1.55 [95% CI, 1.08–2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76–2.15] ; OR, 0.73 [95% CI, 0.37–1.43], respectively) and was not associated with 1‐year mortality (HR, 1.09 [95% CI, 0.83–1.44] ; HR, 0.82 [95% CI, 0.57–1.18], respectively) than appropriate DOAC. Conclusions Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first‐line therapy over VKA.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2653953-6
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