bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Adding Ezetimibe to Statin Therapy Among Women and Men: Insight From IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)
Authors: Kato Eri Toda , Cannon Christopher P. , Blazing Michael A. , Bohula Erin , Guneri Sema , White Jennifer A. , Murphy Sabina A. , Park Jeong‐Gun , Braunwald Eugene , Giugliano Robert P. 
Published: November 2017

Background

IMPROVE
‐
IT
(Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex.

Methods and Results

In
IMPROVE
‐
IT
, patients with acute coronary syndrome and low‐density lipoprotein cholesterol of 50 to 125 mg/dL were randomized to placebo/simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg. They were followed up for a median of 6 years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization ≥30 days, and stroke. Among 18 144 patients in
IMPROVE
‐
IT
, 4416 (24%) were women. At 12 months, the addition of ezetimibe to simvastatin significantly reduced low‐density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7 mg/dL in men and 16.4 mg/dL in women). Women receiving ezetimibe/simvastatin had a 12% risk reduction over those receiving placebo/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79–0.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90–1.01;
P
=0.26 for interaction). When the total number of primary events was considered, women had an 18% reduction with the addition of ezetimibe (relative risk, 95% confidence interval, 0.81; 0.71–0.94) and men had a 6% reduction (relative risk, 0.94; 95% confidence interval, 0.87–1.02;
P
=0.08 for interaction). The addition of ezetimibe did not increase the rates of safety events in either women or men.

Conclusions

IMPROVE
‐
IT
demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid‐lowering therapy to optimize cardiovascular outcomes.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00202878.
Hypertension in Obese Black Women is Not Caused by Increased Sympathetic Vascular Tone
Authors: Marinos Alejandro , Gamboa Alfredo , Celedonio Jorge E. , Preheim Brock A. , Okamoto Luis E. , Ramirez Claudia E. , Arnold Amy C. , Diedrich Andre , Biaggioni Italo , Shibao Cyndya A. 
Published: November 2017

Background
Black women have one of the highest prevalence rates of hypertension and obesity in the United States. We previously reported that sympathetic activation induced by obesity is a significant contributor to hypertension in white patients. It is unknown whether sympathetic activity similarly contributes to hypertension in obese black women.

Methods and Results

We studied 42 obese women (16 white, body mass index 36±4 kg/m
2
, 44% with hypertension; 26 black, body mass index 35±4 kg/m
2
, 46% with hypertension). Antihypertensive medications were discontinued for 2 weeks before the day of the study. All patients underwent complete autonomic blockade with trimethaphan at a dosage of 4 mg/min. Resting sympathetic activity determined from muscle sympathetic nerve recordings was similar between obese black women with hypertension and those with normotension. In whites, sympathetic activity was elevated in obese patients with hypertension compared with normotension; the decrease in mean arterial blood pressure produced by trimethaphan was greater in obese white patients with hypertension compared with those with normotension (−26.8±9.7 mm Hg versus −14.8±7.9 mm Hg,
P
=0.02). In contrast, there was no difference in the depressor responses induced by trimethaphan between obese black women with hypertension and those with normotension (−15.5±10.5 mm Hg versus −12.3±10.2 mm Hg,
P
=0.45). Mean arterial blood pressure remained elevated in obese blacks with hypertension compared with those with normotension during trimethaphan infusion (83.7±15.0 mm Hg versus 71.7±9.8 mm Hg,
P
=0.02). Heart rate increased similarly with trimethaphan between white (
P
=0.11) and black (
P
=0.76) women with hypertension and normotension.

Conclusions
These findings suggest that sympathetic activity does not contribute to hypertension in obese black women and provide further evidence for racial differences in hypertension mechanisms.
Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double‐Blind Randomized Controlled Trial
Authors: MacDonald Thomas M. , Williams Bryan , Webb David J. , Morant Steve , Caulfield Mark , Cruickshank J. Kennedy , Ford Ian , Sever Peter , Mackenzie Isla S. , Padmanabhan Sandosh , McCann Gerald P. , Salsbury Jackie , McInnes Gordon , Brown Morris J. ,   for The British Hypertension Society Programme of Prevention And Treatment of Hypertension With Algorithm‐based Therapy (PATHWAY)
Published: November 2017

Background
Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches.

Methods and Results

We performed a 1‐year, double‐blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (
BP
) ≥150 mm Hg or diastolic
BP
≥95 mm Hg. In phase 1 (weeks 0–16), patients were randomly assigned to initial monotherapy (losartan 50–100 mg or hydrochlorothiazide 12.5–25 mg crossing over at 8 weeks), or initial combination (losartan 50–100 mg plus hydrochlorothiazide 12.5–25 mg). In phase 2 (weeks 17–32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33–52), amlodipine with or without doxazosin could be added to achieve target
BP
. Hierarchical primary outcomes were the difference from baseline in home systolic
BP
, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7–6.0 mm Hg) less over 32 weeks (
P
<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: −0.4 to 2.8 mm Hg],
P
=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events.

Conclusions
Initial combination therapy can be recommended for patients with BP >150/95 mm Hg.

Clinical Trial Registration

URL
:
http://www.ClinicalTrials.gov
. Unique identifier:
NCT
00994617.
Predictors of Mortality in Patients With Severe Ischemic Cardiomyopathy Undergoing Surgical Mitral Valve Intervention
Authors: Kusunose Kenya , Obuchowski Nancy A. , Gillinov Marc , Popovic Zoran B. , Flamm Scott D. , Griffin Brian P. , Kwon Deborah H. 
Published: November 2017

Background

Ischemic mitral regurgitation is associated with substantial risk of death. Although surgical mitral valve intervention (
MV
i) may improve symptoms, it has not been shown to improve survival. The aim of this study was to identify predictors of mortality in patients with ischemic mitral regurgitation and
MV
i.

Methods and Results

We evaluated 117 consecutive patients (age, 65±10 years) with advanced ischemic cardiomyopathy who underwent cardiac magnetic resonance and subsequent
MV
i between January 1, 2002 and January 1, 2012. Cardiac magnetic resonance was used to assess left ventricular remodeling and myocardial scarring. The effective regurgitant orifice area was calculated from the proximal isovelocity surface area by echocardiography. There were 43 deaths (37%) during follow‐up (median, 62 months). On multivariable analysis, age ≥70 years (
P
=0.013), diabetes mellitus (
P
=0.001), dyslipidemia (
P
=0.012), papillary muscle scar (
P
=0.010), incomplete revascularization (
P
=0.001), and total scar %×effective regurgitant orifice area ≥0.20 cm
2
(
P
=0.005) were each independently associated with all‐cause mortality. Although patients with effective regurgitant orifice area <0.2 cm
2
at baseline demonstrated an increased hazard ratio of 3.3 for every 10% increase in scar, the hazard ratio increased to 9 for every 10% increase in scar in those with baseline effective regurgitant orifice area ≥0.20 cm
2
. Mortality also was significantly higher in patients with incomplete revascularization compared with those with vascularized viable myocardium (61% versus 28%;
P
<0.001).

Conclusions

Increased total scar burden and the presence of incomplete revascularization are powerful predictors of mortality in patients with advanced ischemic cardiomyopathy undergoing
MV
i. Viability assessment with cardiac magnetic resonance imaging can identify which patients with ischemic mitral regurgitation are at highest risk for mortality after surgical
MV
i.
Very Late Pathological Responses to Cobalt–Chromium Everolimus‐Eluting, Stainless Steel Sirolimus‐Eluting, and Cobalt–Chromium Bare Metal Stents in Humans
Authors: Mori Hiroyoshi , Atmakuri Dheeraj R. , Torii Sho , Braumann Ryan , Smith Samantha , Jinnouchi Hiroyuki , Gupta Anuj , Harari Emanuel , Shkullaku Melsi , Kutys Robert , Fowler David , Romero Maria , Virmani Renu , Finn Aloke V. 
Published: November 2017

Background

The “very late” clinical outcomes for durable polymer drug‐eluting stents and bare metal stents (
BMSs
) have been shown to be dissimilar in clinical studies. Conceptually, the long‐term vascular compatibility of
BMSs
is still regarded to be superior to drug‐eluting stents; however, no pathologic study to date has specifically addressed this issue. We evaluated the very late (≥1 year) pathologic responses to durable polymer drug‐eluting stents (cobalt–chromium [CoCr] everolimus‐eluting stents [
EESs
] and stainless steel sirolimus‐eluting stents [
SS
‐
SESs
]) versus
BMSs
(CoCr‐
BMSs
).

Methods and Results

From the
CVP
ath stent registry, we studied a total of 119 lesions (40 CoCr‐
EESs
, 44
SS
‐
SES
s, 35 CoCr‐
BMS
s) from 92 autopsy cases with a duration ranging from 1 to 5 years. Sections of stented coronary segments were pathologically analyzed. Inflammation score and the percentage of struts with giant cells were lowest in CoCr‐
EESs
(median inflammation score: 0.6; median percentage of struts with giant cells: 3.8%) followed by CoCr‐
BMSs
(median inflammation score: 1.3 [
P
<0.01]; median percentage of struts with giant cells: 8.9% [
P
=0.02]) and SS‐
SESs
(median inflammation score: 1.7 [
P
<0.01]; median percentage of struts with giant cells: 15.3% [
P
<0.01]). Polymer delamination was observed exclusively in
SS
‐
SESs
and was associated with increased inflammatory and giant cell reactions. The prevalence of neoatherosclerosis with CoCr‐
EESs
(50%) was significantly less than with
SS
‐
SESs
(77%,
P
=0.02) but significantly greater than with CoCr‐
BMSs
(20%,
P
<0.01).

Conclusions

CoCr‐
EESs
,
SS
‐
SESs
, and
BMSs
each demonstrated distinct vascular responses. CoCr‐
EESs
demonstrated the least inflammation, near‐equivalent healing to
BMSs
, and lower neointimal formation. These results challenge the belief that
BMSs
have superior biocompatibility compared with some polymeric coated drug‐eluting stents and may have implications for future stent design.
Association of procalcitonin values and bacterial infections in pediatric patients receiving extracorporeal membrane oxygenation
Authors: Tan Vi Ean , Moore Wayne S. , Chopra Arun , Cies Jeffrey J. 
Published: November 2017

Objective: There is increasing data in pediatrics demonstrating procalcitonin (PCT) is more sensitive and specific than other biomarkers in the setting of bacterial infections. However, the use of PCT in neonatal and pediatric extracorporeal membrane oxygenation (ECMO) is not well described. Therefore, the purpose of this study was to describe the clinical utility of PCT in determining the absence or presence of bacterial infections in neonatal and pediatric patients on ECMO. Methods: This was a retrospective electronic medical record (EMR) review of data between January 1, 2010 to June 30, 2016 at a single, free-standing, children ’s hospital. All patients on ECMO with ≥1 PCT level obtained while receiving ECMO support were eligible for inclusion. The EMR was searched for chest radiographs (CXR) and bacterial culture results (urine, blood, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) and respiratory cultures). All bacterial and viral cultures obtained within 5 days of PCT levels being obtained were analyzed. PCT levels of 0.5, 0.9, 1.0, 1.4 and 2.0 were used as the initial cut-off values for the analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) and likelihood ratios were calculated for each of the PCT levels. Results: Twenty-seven patients met the inclusion criteria and contributed 193 PCT values for the analysis. The median age was 8 months (range 0 days to 18 years). Linear regression analysis demonstrated that a PCT cut-off of 0.5, 0.9 and 1.4 predicted the presence of a bacterial infection. The PCT value with the most utility was 0.5, with a sensitivity of 92%, a specificity of 43%, a positive predictive value of 60% and a negative predictive value (NPV) of 86%. Conclusion: This is the largest data set evaluating PCT in neonatal and pediatric patients on ECMO. A PCT value of 0.5 ng/mL had the most utility for determining the absence or presence of a bacterial infection in the setting of ECMO with a high sensitivity and NPV.
Effect of bariatric surgery on diabetic nephropathy in obese type 2 diabetes patients in a retrospective 2-year study: A local pilot
Authors: Chao Anthony TL , Chee Fang Sum , Lam Benjamin CC , Cheng Anton KS , Low Serena KM , Su Chi Lim 
Published: November 2017

Purpose: To determine the effects of bariatric surgery on albuminuria in obese patients with type 2 diabetes mellitus. Methods: Retrospective analyses of clinical records of obese patients with type 2 diabetes mellitus who had either micro- or macroalbuminuria and had undergone various bariatric surgery were retrieved from a local hospital database. Their clinical data from follow-up appointments including albuminuria were analysed. Results: Of the 46 subjects with type 2 diabetes mellitus, 15 subjects had diabetic nephropathy and had pre- and post-bariatric surgery urine albumin-to-creatinine ratio or urine protein-to-creatinine ratio data available for analysis; 13 out of the 15 subjects (86.7%) showed improvement of urine albumin-to-creatinine ratio or urine protein-to-creatinine ratio after surgery; 2 showed equivocal results; 9 of 13 subjects (69.2%) showed remission of diabetic nephropathy; 7 of these 9 patients had microalbuminuria before surgery, 2 had macroalbuminuria before surgery. There were significant improvements to glycosylated haemoglobin, fasting plasma glucose, blood pressure and body weight post surgery. The usage of insulin and oral medications dropped significantly post surgery for all subjects. Conclusion: This study shows that bariatric surgery significantly improves diabetic nephropathy in obese type 2 diabetes mellitus subjects. The results suggest that in our local type 2 diabetes mellitus patients, it is possible not only to improve metabolic parameters, but also to reverse what may be considered established microvascular complications by means of bariatric surgery.
Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs
Authors: Francica Joseph R. , Zak Daniel E. , Linde Caitlyn , Siena Emilio , Johnson Carrie , Juraska Michal , Yates Nicole L. , Gunn Bronwyn , De Gregorio Ennio , Flynn Barbara J. , Valiante Nicholas M. , Malyala Padma , Barnett Susan W. , Sarkar Pampi , Singh Manmohan , Jain Siddhartha , Ackerman Margaret , Alam Munir , Ferrari Guido , Salazar Andres , Tomaras Georgia D. , O’Hagan Derek T. , Aderem Alan , Alter Galit , Seder Robert A. 
Published: November 2017

Key PointsTLR4 and 7 agonists improve titers when coformulated with alum but not an emulsion formulation, but do not impact the titer half-lives. Alum/TLR7 and pIC:LC are potent adjuvant formulations that improve the magnitude and quality of humoral and cellular responses to HIV Env.
Intensive care unit patients with lower respiratory tract nosocomial infections: the ENIRRIs project
Authors: De Pascale Gennaro , Ranzani Otavio T. , Nseir Saad , Chastre Jean , Welte Tobias , Antonelli Massimo , Navalesi Paolo , Garofalo Eugenio , Bruni Andrea , Coelho Luis Miguel , Skoczynski Szymon , Longhini Federico , Taccone Fabio Silvio , Grimaldi David , Salzer Helmut J.F. , Lange Christoph , Froes Filipe , Artigas Antoni , Díaz Emili , Vallés Jordi , Rodríguez Alejandro , Panigada Mauro , Comellini Vittoria , Fasano Luca , Soave Paolo M. , Spinazzola Giorgia , Luyt Charles-Edouard , Alvarez-Lerma Francisco , Marin Judith , Masclans Joan Ramon , Chiumello Davide , Pezzi Angelo , Schultz Marcus , Mohamed Hafiz , Van Der Eerden Menno , Hoek Roger A.S. , Gommers D.A.M.P.J. , Pasquale Marta Di , Civljak Rok , Kutleša Marko , Bassetti Matteo , Dimopoulos George , Nava Stefano , Rios Fernando , Zampieri Fernando G. , Povoa Pedro , Bos Lieuwe D. , Aliberti Stefano , Torres Antoni , Martín-Loeches Ignacio 
Published: November 2017

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects.A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.
Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills
Authors: Chai Peter R. , Carreiro Stephanie , Innes Brendan J. , Chapman Brittany , Schreiber Kristin L. , Edwards Robert R. , Carrico Adam W. , Boyer Edward W. 
Published: November 2017

BACKGROUND:
Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction.

METHODS:
We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion.

RESULTS:
In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3–9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest opioids at 1 week. There was substantial variability in ingestion patterns between individuals.

CONCLUSIONS:
The utilization patterns of individuals with acute fracture pain could be captured using a digital pill system and revealed a median opioid ingestion of 45-mg morphine equivalents for acute pain over 7 days. Seven participants ceased using opioids within 4 days after discharge from the emergency department, although operative repair was associated with longer use. This digital pill system was able to measure changes in and patterns of opioid self-dosing, which varied between patients.