bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome measures to be considered on asthma in elderly
Authors: González-Díaz Sandra Nora , Villarreal-Gonzalez Rosalaura Virginia , Lira-Quezada Cindy Elizabeth De , Guzman-Avilan Rosa Ivett 
Published: February 2019

Purpose of review
Asthma is a chronic heterogeneous respiratory disease which is characterized by airflow limitation and variable respiratory symptoms. Asthma in patients more than 65 years of age has an important negative impact on quality of life. The pathophysiology and treatment of asthma in older patients are not as well identified as in younger groups of ages. In this review we intend to outline characteristics found in elderly adults which distinguish them from other age groups of patients with asthma.

Recent findings
With increasing age, there are alterations in the innate and adaptive immune responses, known as ‘immunosenescence.’ These age-associated modifications include an altered response after a pathogenic exposure or tissue injury, moderately mediated through an irreversible loss of cellular replication and defective tissue repair.

Summary
Asthma is a consequence of complex gene–environment interactions, with diversity in clinical presentation and the type and intensity of airway inflammation and remodeling. Age-associated changes in lung physiology and morphology may occur and contribute to asthma. Aging is correlated with a notable decrease in elastic recoil, greater chest wall rigidity, and poor respiratory muscle strength. Underreporting of symptoms by elderly patients is common because of multiple underlying causes.

Video abstract

http://links.lww.com/COAI/A17.
Initiation and Rapid Titration of Methadone in an Acute Care Setting for the Treatment of Opioid Use Disorder: A Case Report
Authors: Hemmons Patrick , Bach Paxton , Colizza Kate , Nolan Seonaid 
Published: February 2019

Background:
Although methadone is an effective treatment for opioid use disorder, its initiation requires prescribing at a subtherapeutic dose with subsequent titration to a therapeutic dose over many weeks. Accordingly, the methadone induction period can be a challenging one for individuals and can be associated with an increased risk for ongoing illicit drug use and consequently overdose. Given its capacity for regular clinical assessments, acute care settings may offer a unique opportunity to reduce the duration of the induction period for methadone maintenance therapy.

Case summary:
We report a case of an individual who successfully completed initiation and rapid methadone titration for treatment of opioid use disorder in an acute care setting.

Discussion:
Utilizing divided dosing intervals and regular monitoring for toxicity, the patient received a cumulative methadone dose of 130 mg total within the first 48 hours of admission with continuation of a similar dose subsequently. No adverse events occurred over a 9-day follow-up period. The case report described here highlights the potential acute care settings may offer for the successful initiation and rapid titration of methadone for the treatment of opioid use disorder. Such an approach could significantly reduce the induction period associated with methadone maintenance therapy and its associated negative outcomes including ongoing illicit substance use and risk for overdose.
Contemporary Trends in Cesarean Delivery Utilization for Live Births Between 22 0/7 and 23 6/7 Weeks of Gestation
Authors: Rossi Robert M. , Hall Eric , DeFranco Emily A. 
Published: February 2019

OBJECTIVE:
In 2014, the Society for Maternal-Fetal Medicine, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists published an executive summary of a joint workshop to establish obstetric interventions to be considered for periviable births. We sought to evaluate changes in practice patterns since the publication of these guidelines.

METHODS:
We conducted a population-based cohort study of all singleton live births delivered between 22 0/7 and 23 6/7 weeks of gestation in the United States within two time epochs: pre–executive summary (Epoch 1: 2012–2013) and post–executive summary (Epoch 2: 2015–2016) guideline release. The primary outcome was the difference in the rate of cesarean delivery between pre–executive summary and post–executive summary guideline publication. Secondary outcomes included differences in rates of individual and composite neonatal interventions (neonatal intensive care unit admission, ventilation, surfactant and antibiotic administration), maternal adverse outcomes (intensive care unit admission, transfusion, hysterectomy, uterine rupture), and neonatal mortality. Multivariable logistic regression estimated the association of delivery epoch with outcomes.

RESULTS:
There were 15,846,405 live births in the United States between 2012–2013 and 2015–2016, of which 14,799 (0.1%) were singletons delivered between 22 and 24 weeks of gestation. Among these live births, 7,374 (52.3%) were delivered in Epoch 1 and 7,425 (47.7%) in Epoch 2. Cesarean delivery rates increased from Epoch 1 to Epoch 2 (24.3% vs 28.4%, P<.001), which was attributable to increased cesarean utilization during the 23rd week (36.3% vs 40.8%, difference 4.5%, 95% CI 2.3–6.6). Likewise, the rate of composite neonatal interventions increased (50.6% vs 56.9%, difference 6.3%, 95% CI 4.6–8.0) between Epochs 1 and 2, in association with a slight reduction in neonatal mortality (67.2% vs 64.6%, P=.009). There was no statistically significant difference in composite (8.9% vs 9.5%, P=.261) adverse maternal outcomes between delivery epochs.

CONCLUSION:
The frequency of delivery by cesarean in the 23rd week increased by 4.5% after publication of the periviable birth executive summary. The observed increase in cesarean delivery and composite neonatal interventions between delivery cohorts was associated with a small reduction in neonatal mortality.
Ulipristal Acetate for Disseminated Peritoneal Leiomyomatosis
Authors: Benlolo Samantha , Papillon-Smith Jessica , Murji Ally 
Published: February 2019

BACKGROUND:
Disseminated peritoneal leiomyomatosis is a rare condition manifesting as hormone-sensitive soft tissue nodules lining the peritoneal cavity. Given the extensiveness of this disease, surgical management is challenging, making hormonal suppression the primary treatment.

CASE:
A 23-year-old woman presenting with abdominal pain was found to have innumerable abdominopelvic nodules on imaging. Biopsy of these lesions was consistent with disseminated peritoneal leiomyomatosis. Treatment using leuprolide acetate led to satisfactory results but was discontinued owing to vasomotor symptoms. Treatment was changed to cyclic ulipristal acetate, a selective progesterone receptor modulator. Over the past 2 years, the patient has completed five 3-month courses of ulipristal acetate with excellent symptomatic and radiologic response.

CONCLUSION:
The use of ulipristal acetate may be an effective, novel therapeutic option for the management of disseminated peritoneal leiomyomatosis.
Noninvasive Prenatal Whole Genome Sequencing
Authors: Sullivan Haley K. , Bayefsky Michelle , Wakim Paul G. , Huddleston Kathi , Biesecker Barbara B. , Hull Sara Chandros , Berkman Benjamin E. 
Published: February 2019

OBJECTIVE:
To assess pregnant women's views and preferences on noninvasive prenatal whole genome sequencing.

METHODS:
A survey was offered to 805 pregnant women receiving prenatal care in practices affiliated with a large, tertiary care maternity hospital. Respondents were asked to envision undergoing prenatal whole genome sequencing and discuss their preferences and reasons for receiving different categories of genomic results, organized by actionability, severity, prevalence, and age of onset. The survey also queried respondents on their preferred role for clinicians in prenatal whole genome sequencing decision-making, and on their demographics and genetic literacy.

RESULTS:
From June to August 2017, a total of 553 respondents returned the survey (response rate=68.7%). Respondents were most likely to want information regarding serious treatable childhood-onset conditions (89.7%) and least likely to want to receive information about nonmedical traits from prenatal whole genome sequencing (40%). The most frequently cited reason for wanting medical prenatal whole genome sequencing results was “to prepare financially, medically, or psychologically for a child with special needs.” In total, 10.5% of respondents wanted clear recommendations from clinicians about the categories of information that are most appropriate to test for, 44.7% wanted clear recommendations plus all options presented, 26.2% wanted all options presented and joint decision-making, and 13.2% wanted all options presented and independent decision-making.

CONCLUSION:
Respondents generally preferred to receive all categories of genetic results pertaining to medical conditions and wanted the information to prepare. More than half of respondents wanted (at minimum) clear recommendations from clinicians when deciding which prenatal whole genome sequencing results to receive.
Joints for joints: cannabinoids in the treatment of rheumatoid arthritis
Authors: Lowin Torsten , Schneider Matthias , Pongratz Georg 
Published: February 2019

Purpose of review
An increasing number of patients with rheumatoid arthritis (RA) are using cannabis to treat their symptoms, although systematic studies regarding efficacy in RA are lacking. Within this review we will give an overview on the overall effects of cannabinoids in inflammation and why they might be useful in the treatment of RA.

Recent findings
Peripherally, cannabinoids show anti-inflammatory effects by activating cannabinoid type 2 receptors (CB2) which decrease cytokine production and immune cell mobilization. In contrast, cannabinoid type 1 receptor (CB1) activation on immune cells is proinflammatory while CB1 antagonism provides anti-inflammatory effects by increasing β2-adrenergic signaling in the joint and secondary lymphoid organs. In addition, the nonpsychotropic cannabinoid, cannabidiol (CBD) demonstrated antiarthritic effects independent of cannabinoid receptors. In addition to controlling inflammation, cannabinoids reduce pain by activating central and peripheral CB1, peripheral CB2 receptors and CBD-sensitive noncannabinoid receptor targets.

Summary
Cannabinoids might be a suitable treatment for RA, but it is important to target the right receptors in the right place. For clinical studies, we propose a combination of a CB2 agonist to decrease cytokine production, a peripheral CB1 antagonist to prevent detrimental CB1 signaling and to support anti-inflammatory effects of CB2 via activation of β2-adrenergic receptors and CBD to induce cannabinoid-receptor-independent anti-inflammatory effects.
Neutropenic Enterocolitis in Critically Ill Patients: Spectrum of the Disease and Risk of Invasive Fungal Disease
Authors: Duceau Baptiste , Picard Muriel , Pirracchio Romain , Wanquet Anne , Pène Frédéric , Merceron Sybille , Mokart Djamel , Moreau Anne-Sophie , Lengliné Etienne , Canet Emmanuel , Lemiale Virginie , Mariotte Eric , Azoulay Elie , Zafrani Lara 
Published: February 2019

Objectives:Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease.Design:A multicentric retrospective cohort study between January 2010 and August 2017.Setting:Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network.Patients:Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficilecolitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded.Interventions:None.Measurement and Main Results:We included 134 patients (median Sequential Organ Failure Assessment 10 [8–12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n= 65, 48.5%), lymphoma (n= 49, 36.6%), solid tumor (n= 14, 10.4%), and myeloma (n= 4, 3.0%). Patients were neutropenic during a median of 14 days (9–22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32–7.56;p= 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21–3.31;p= 0.016) were independently associated with invasive fungal disease.Conclusions:The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.
Potential role of cyclin-dependent kinase 4/6 inhibitors in the treatment of squamous cell carcinoma of the head and neck
Authors: van Caloen Gabrielle , Machiels Jean-Pascal 
Published: February 2019

Purpose of review
Human papillomavirus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN) is mainly driven by genetic aberrations involved in the cell cycle pathway resulting in cyclin-dependent kinase (CDK) 4 and 6 activation. This supports the investigation of the activity of CDK4/6 inhibitors in this disease. We review the therapeutic potential of CDK4/6 inhibitors in SCCHN.

Recent findings
CDK4/6 inhibitors in monotherapy have demonstrated cytostatic activity in HPV-negative SCCHN. Combination with epidermal growth factor inhibitors, with phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathways inhibitors or with immunotherapy, have shown promising preclinical efficacy. No strong predictive biomarkers of response or resistance have been firmly identified.
Phase I clinical trials have demonstrated that palbociclib or ribociclib in combination with cetuximab is well tolerated. A phase II single-arm trial combining palbociclib/cetuximab has shown promising results.

Summary
Inhibition of CDK4/6 represents a new potential treatment for HPV-negative SCCHN patients. Randomized clinical trials that investigate these compounds in an unbiased manner are needed to fully evaluate their efficacy. However, it is unlikely that all the patients will benefit from this new approach. To determine a molecular profile/phenotype that will predict CDK4/6 inhibitor activity, researchers will have to take into account simultaneously occurring events in the cyclin-D/CDK4/CDK6/retinoblastoma and associated pathways.
Achieving a Complete Clinical Response After Neoadjuvant Chemoradiation That Does Not Require Surgical Resection: It May Take Longer Than You Think!
Authors: Habr-Gama Angelita , São Julião Guilherme P. , Fernandez Laura M. , Vailati Bruna B. , Andrade Andres , Araújo Sérgio E. A. , Gama-Rodrigues Joaquim , Perez Rodrigo O. 
Published: February 2019

BACKGROUND:
Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed by organ-preserving strategies and acceptable long-term outcomes. Controversy still exists regarding optimal timing for the assessment of tumor response after neoadjuvant chemoradiation.

OBJECTIVE:
The purpose of this study was to estimate the time interval for achieving complete clinical response using strict endoscopic and clinical criteria after a single neoadjuvant chemoradiation regimen.

DESIGN:
This was a retrospective review of consecutive patients managed by 54-Gy and consolidation 5-fluorouracil–based chemotherapy. Assessment of response was performed at 10 weeks after radiation. Patients with suspected complete clinical response were offered watch-and-wait strategy and reassessment every 6 to 8 weeks until achievement of strict criteria of complete clinical response or overt residual cancer.

SETTINGS:
This study was conducted at a single tertiary care center.

PATIENTS:
Patients with complete clinical response who underwent a successful watch-and-wait strategy until last follow-up were eligible. Dates of radiation completion and achievement of strict endoscopic and clinical criteria (mucosal whitening, teleangiectasia, and no ulceration or irregularity) were recorded. Patients with incomplete response or with initial complete clinical response followed by local recurrence or regrowth were excluded.

MAIN OUTCOMES MEASURES:
The distribution of time intervals between completion of radiation and achievement of strict complete clinical response was measured. Patients who achieved early complete clinical response (≤16 wk) were compared with late complete clinical response (>16 wk).

RESULTS:
A total of 49 patients achieved complete clinical response and were successfully managed nonoperatively. A median interval of 18.7 weeks was observed for achieving strict complete clinical response. Only 38% of patients achieved complete clinical response between 10 and 16 weeks from radiation completion. Patients with earlier cT status (cT2/T3a) achieved a complete clinical response significantly earlier when compared with those patients with more advanced disease (T3b-d/4; 19 vs 26 wk; p = 0.03).

LIMITATIONS:
This was a retrospective study with a small sample size.

CONCLUSIONS:
Assessment at 10 to 16 weeks may detect a minority of patients who achieve complete clinical response without additional recurrence after neoadjuvant chemoradiation. Patients suspected for a complete clinical response should be considered for reassessment beyond 16 weeks before definitive management when considered for a watch and wait strategy. See Video Abstract at http://links.lww.com/DCR/A901.
Role of Magnification Chromoendoscopy in the Management of Colorectal Neoplastic Lesions Suspicious for Submucosal Invasion
Authors: Kawaguti Fabio S. , Franco Matheus C. , Martins Bruno C. , Segateli Vanderlei , Marques Carlos F. S. , Nahas Caio S. R. , Pinto Rodrigo A. , Safatle-Ribeiro Adriana V. , Ribeiro-Junior Ulysses , Nahas Sergio C. , Maluf-Filho Fauze 
Published: February 2019

BACKGROUND:
Correctly predicting the depth of tumor invasion in the colorectal wall is crucial for successful endoscopic resection of superficial colorectal neoplasms.

OBJECTIVE:
The aim of this study was to assess the accuracy of magnifying chromoendoscopy in a Western medical center to predict the depth of invasion by the pit pattern classification in patients with colorectal neoplasms with a high risk of submucosal invasion.

DESIGN:
This single-center retrospective study, from a prospectively collected database, was conducted between April 2009 and June 2015.

SETTINGS:
The study was conducted at a single academic center.

PATIENTS:
Consecutive patients with colorectal neoplasms with high risk of submucosal invasion were included. These tumors were defined by large (≥20 mm) sessile polyps (nonpedunculated), laterally spreading tumors, or depressed lesions of any size.

INTERVENTIONS:
Patients underwent magnifying chromoendoscopy and were classified according to the Kudo pit pattern. The therapeutic decision, endoscopic or surgery, was defined by the magnification assessment.

MAIN OUTCOME MEASURES:
Sensitivity, specificity, and positive and negative predictive values of magnifying chromoendoscopy for assessment of these lesions were determined.

RESULTS:
A total of 123 lesions were included, with a mean size of 54.0 ± 37.1 mm. Preoperative magnifying chromoendoscopy with pit pattern classification had 73.3% sensitivity, 100% specificity, 100% positive predictive value, 96.4% negative predictive value, and 96.7% accuracy to predict depth of invasion and consequently to guide the appropriate treatment. Thirty-three rectal lesions were also examined by MRI, and 31 were diagnosed as T2 lesions. Twenty two (70.1%) of these lesions were diagnosed as noninvasive by magnifying colonoscopy, were treated by endoscopic resection, and met the curative criteria.

LIMITATIONS:
This was a single-center retrospective study with a single expert endoscopist experience.

CONCLUSIONS:
Magnifying chromoendoscopy is highly accurate for assessing colorectal neoplasms suspicious for submucosal invasion and can help to select the most appropriate treatment. See Video Abstract at http://links.lww.com/DCR/A920.
Radiofrequency Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation: Meta-analysis of Safety and Efficacy
Authors: Yi Fang , Hou Wenbo , Zhou Chao , Yin Yuxia , Lu Shoutao , Duan Cuihai , Cao MingKun , Li Maoquan , Toft Egon Steen , Zhang Haijun 
Published: February 2019

Background:
Radiofrequency ablation (RFA) and antiarrhythmic drugs (AADs) are the main treatments used for atrial fibrillation (AF). In recent years, a number of articles comparing the 2 treatments have begun to emerge. Though, the influence of follow-up time in the meta-analysis was not considered in these articles. However, more recently, large-scale clinical trial articles have included follow-up with the patients up to 5 years after treatment. Therefore, the aim of this study was to assess the impact of variable follow-up times on the recurrence of AF by observing both the short-term and long-term efficacy and safety of catheter ablation and AADs for the treatment of AF.

Methods and Results:
The primary investigators of eligible randomized controlled trials were invited to contribute standardized outcome data. Random effect summary estimates were calculated as standardized mean differences and odds ratios with 95% confidence intervals for continuous and binary outcomes. In this study, 9 randomized controlled trials (n = 1542 patients) were included. The rate of recurrence of AF with no limit on follow-up time, >12 months, >18 months, >24 months, >30 months, and approximately 36 months was compared. Furthermore, the gap between the RFA and AAD groups in the recurrence rate of AF was found to decrease inversely to follow-up time. When the follow-up time reached 24 months, the difference between RFA and AAD was relatively stable with an odds ratio of 0.45 (95% confidence interval: 0.32–0.62). Overall, RFA decreased adverse events in the remaining trials; however, AAD performed better in terms of safety and had fewer adverse events with RFA usually causing more serious complications.

Conclusion:
RFA is more advantageous in terms of recurrence rate of AF than drug therapy. In addition, the analysis suggests that this effect persists during long-term follow-up; however, these benefits appear to decrease with longer follow-up time. Finally, AAD performed better in terms of safety and had fewer adverse events.