Coronary revascularization outcomes in relation to skilled nursing facility use following hospital discharge

BackgroundObservational analyses comparing coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) among elderly or frail patients are likely biased by treatment selection. PCI is typically chosen for frail patients, while CABG is more common for patients with good recovery potential.HypothesisWe hypothesized that skilled nursing facility (SNF) use after revascularization is a measure of relative frailty associated with outcomes following coronary revascularization.MethodsWe used a 20 percent sample of Medicare beneficiaries aged 65 years or older who received inpatient PCI or CABG between 2007–2014. Key explanatory variables were the revascularization strategy and SNF use after revascularization. We used Cox regression to evaluate death and repeat revascularization within one year and logistic regression to evaluate SNF use and 30‐day readmissions/death.ResultsCABG patients were 25.1 percentage points [95% confidence interval: 24.7, 25.5] more likely to use SNF following revascularization than inpatient PCI patients. SNF use was associated with a higher death rate (hazard ratio (HR): 3.19 [3.02, 3.37]) and a 16.2 percentage point (15.5, 16.9) increase in 30‐day readmissions/death. Among patients with SNF use, CABG was associated with a decrease in 30‐day readmissions/death compared to PCI.ConclusionsWhile CABG was associated with higher rates of SNF use and 30‐day readmission/death overall, CABG was associated with significantly lower rates of 30‐day readmissions/death among patients with SNF use. The findings suggest that caution is needed in treatment selection for patients at high‐risk for SNF use and that selection of inpatient PCI over CABG may be associated with frailty and worse outcomes for some patients.     

Changes and determination of dosing recommendations for medicinal products recently authorised in the European Union

Introduction: The quantity and quality of data for determining the dose and treatment schedule of medicinal products is directly related to how safe and efficacious these medicines are and how successful they can be used to treat patients.

Areas covered: This review provides an analysis of dose-related label modifications of recently approved drugs. It shows which areas could benefit from a better dose–exposure–response understanding, both during initial assessment and after marketing authorisation. This analysis highlights regulators’ considerations in dosage evaluations and provides reflections for drug developers on how to ensure best possible dose selection in the interest of the patients.

Expert opinion: Using modelling and simulation, pharmacogenomics, population pharmacokinetics, physiologically based pharmacokinetic models and drug–drug interaction studies in conjunction with well-designed clinical trials will improve the understanding of the pharmacology of medicines, of the physiology of the disease and of the dose–exposure–response relationship during drug development. More focus should be given to the investigation of dose and regimens for special populations before applying for marketing authorisation. Consequently, regulators could review dose–exposure–response data with more certainty and better define dose recommendations in the label.     

Developing a prototype for short-term psychodynamic (supportive-expressive) therapy: An empirical study with the psychotherapy process Q-set

Objective: A Psychotherapy Process Q-set (PQS) prototype characteristic of short-term psychodynamic therapy (STPP) does not yet exist. Method: Experts in supportive-expressive (SE) therapy used the 100-Item PQS questionnaire to rate an ideal short-term SE therapy. Results: Agreement between raters was high (Cronbach's alpha?=?0.94). The prototype for SE therapy showed a significant correlation with the psychoanalytic prototype, but with 28% of variance explained, the majority of variance of the former was not explained by the latter or vice versa. Furthermore, the SE prototype showed significant correlations with the cognitive-behavioral prototype and the prototype of interpersonal therapy by Ablon and Jones (r?=?0.69, 0.43). Conclusions: We recommend using the PQS prototype presented here for future process research on STPP.     

Dopaminergic receptor blockade changes a functional connectivity network centred on the amygdala

Resting‐state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro‐psychiatric conditions. One approach that has recently gained prominence in this regard—and which we use in this study—is to investigate how resting‐state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2‐receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network‐based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2‐receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting‐state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment. Hum Brain Mapp 37:4148–4157, 2016. © 2016 Wiley Periodicals, Inc.     

Time course of facial emotion processing in women with borderline personality disorder: an ERP study

BackgroundBorderline personality disorder (BPD) is characterized by a negative perception of others. Previous studies have revealed deficits and biases in facial emotion recognition. This study investigates the behavioural and electrophysiological correlates underlying facial emotion processing in individuals with BPD.MethodsThe present study was conducted between July 2012 and May 2014. In an emotion classification task, unmedicated female patients with BPD as well as healthy women had to classify faces displaying blends of anger and happiness while the electroencephalogram was recorded. We analyzed visual event-related potentials (ERPs) reflecting early (P100), structural (N170) and categorical (P300) facial processing in addition to behavioural responses.ResultsWe included 36 women with BPD and 29 controls in our analysis. Patients with BPD were more likely than controls to classify predominantly happy faces as angry. Independent of facial emotion, women with BPD showed enhanced early occipital P100 amplitudes. Additionally, temporo-occipital N170 amplitudes were reduced at right hemispherical electrode sites. Centroparietal P300 amplitudes were reduced particularly for predominantly happy faces and increased for highly angry faces in women with BPD, whereas in healthy volunteers this component was modulated by both angry and happy facial affect.LimitationsOur sample included only women, and no clinical control group was investigated.ConclusionOur findings suggest reduced thresholds for facial anger and deficits in the discrimination of facial happiness in individuals with BPD. This biased perception is associated with alterations in very early visual as well as deficient structural and categorical processing of faces. The current data could help to explain the negative perception of others that may be related to the patients’ impairments in interpersonal functioning.     

Evaluation of Mutational Testing of Preneoplastic Barrett's Mucosa by Next-Generation Sequencing of Formalin-Fixed,Paraffin-Embedded Endoscopic Samples?for Detection of Concurrent Dysplasia and?Adenocarcinoma in Barrett's Esophagus

Barrett''s intestinal metaplasia (BIM) may harbor genomic mutations before the histologic appearance of dysplasia and cancer and requires frequent surveillance. We explored next-generation sequencing to detect mutations with the analytical sensitivity required to predict concurrent high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett''s esophagus by testing nonneoplastic BIM. Formalin-fixed, paraffin-embedded (FFPE) routine biopsy or endoscopic mucosal resection samples from 32 patients were tested: nonprogressors to HGD or EAC (BIM-NP) with BIM, who never had a diagnosis of dysplasia or EAC (N = 13); progressors to HGD or EAC (BIM-P) with BIM and a worse diagnosis of HGD or EAC (N = 15); and four BIM-negative samples. No mutations were detected in the BIM-NP (0 of 13) or BIM-negative samples, whereas the BIM-P samples had mutations in 6 (75%) of 8 cases in TP53, APC, and CDKN2A (P = 0.0005), detected in samples with as low as 20% BIM. We found that next-generation sequencing from routine FFPE nonneoplastic Barrett''s esophagus samples can detect multiple mutations in minute areas of BIM with high analytical sensitivity. Next-generation sequencing panels for detection of TP53 and possibly combined mutations in other genes, such as APC and CDKN2A, may be useful in the clinical setting to improve dysplasia and cancer surveillance in patients with Barrett''s esophagus.CME Accreditation Statement: This activity (“JMD 2015 CME Program in Molecular Diagnostics”) has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP). ASCP is accredited by the ACCME to provide continuing medical education for physicians.The ASCP designates this journal-based CME activity (“JMD 2015 CME Program in Molecular Diagnostics”) for a maximum of 36 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.CME Disclosures: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.Esophageal adenocarcinoma (EAC) most frequently develops in patients with Barrett''s esophagus (BE), estimated to affect 3.3 million adults in the United States.¹ BE results from injury of the esophageal mucosa associated with gastroesophageal reflux, which leads to esophagitis and eventually BE. The incidence of EAC has increased greater than fivefold during the past 4 decades in the United States, paralleling the increase in detection of esophageal reflux and diagnosis of BE.² Barrett’s intestinal metaplasia (BIM) is characterized by the replacement of normal squamous esophageal mucosa by columnar epithelium with intestinal metaplasia, often occurring in the background of patches of cardiac, oxyntic, or cardiooxyntic mucosa along the length of the BE. Patients with BE may sequentially progress to low-grade dysplasia, high-grade dysplasia (HGD), and eventually EAC. Patients with BE without dysplasia have a lower EAC risk (0.1% to 0.5% per patient-year) than those with high-grade dysplasia (6% to 19% per patient-year).^3,4 Current guidelines for the prevention of EAC require repeat surveillance endoscopies with biopsies of the Barrett''s mucosa followed by pathological examination to detect BIM and dysplasia.^4–6 Unfortunately, the detection of dysplasia is hampered by sampling errors and high interobserver diagnostic variability.^7–10Known risk factors associated with EAC include male sex, older age, white race, hiatal hernia size, length of Barrett''s epithelium, smoking, and high body mass index.⁶ Recently, it was reported that persistence of BE negative for dysplasia over several endoscopic examinations identifies patients who are at low risk for development of EAC.¹¹It has been hoped that surveillance could potentially be improved by the implementation of risk stratification protocols using both clinical and biological markers because management of BE is costly and inefficient because only a small percentage of patients with BE progress to HGD or EAC.¹² Furthermore, recent data revealed that endoscopic surveillance of patients with BE was not associated with a substantially decreased risk of death from EAC.¹³Biomarkers that can be assessed in random biopsy specimens from Barrett''s mucosa negative for dysplasia with the ability to predict development or concurrent (co-existing) dysplasia elsewhere in the esophagus are warranted to improve surveillance approaches in the BE population. Previously evaluated testing approaches for EAC risk stratification in BE using esophageal biopsy samples include nuclear DNA content abnormalities, such as aneuploidy and tetraploidy; gene copy number alterations, such as loss of heterozygosity of p16 (CDKN2A) and p53 (TP53)^14,15; somatic gene mutations; and hypermethylation of a number of genes.^14,16,17 However, published studies used fresh or frozen tissue or special sampling procedures, which limits their clinical implementation, and data from studies using routine formalin-fixed, paraffin-embedded (FFPE) clinical endoscopic samples replicating the clinical setting of BE patients undergoing endoscopic surveillance have not been reported.⁶Next-generation sequencing (NGS) approaches using nucleic acids obtained from routinely processed FFPE tissues to detect mutations in cancer samples, enabling high analytical sensitivity and detection of low-frequency mutational events, are well established. However, NGS testing of preneoplastic tissues, such as BE, have not been evaluated in routine FFPE clinical samples, and there is no information regarding the minimal percentage of intestinal metaplasis in the tested mucosal tissue that may be considered for mutation testing. Therefore, we hypothesized that targeted NGS may be ideally suited for clinical application in the BE surveillance setting because it can be performed with minimal amounts of DNA from routine FFPE tissue samples, permits biomarker multiplexing, and can reach high sensitivity to detect low-frequency mutational events in heterogeneous BE tissues, where the foci of intestinal metaplasia may be small. Sensitivity of mutation detection by NGS can be 0.5% or lower due to the high level of sequencing coverage, reaching several thousand reads per amplicon when targeted sequencing is used. Therefore, targeted NGS of BE FFPE samples enables the characterization of the mutational status of hundreds to thousands of target functional sites in oncogenes and tumor suppressor genes that may be critical in BE, dysplastic precursor lesions, and EAC in individual biopsy samples collected in the clinical diagnostic setting.We used two NGS-targeted amplicon sequencing technology platforms, the Illumina (San Diego, CA) TruSeq Cancer Panel for Illumina MiSeq platform and the Ion Torrent Ion AmpliSeq Cancer Panel (Life Technologies, Carlsbad, CA), to determine whether mutations of genes known to undergo mutagenesis in esophageal dysplasia or cancer arising in BE could predict the presence of HGD or EAC through testing random nondysplastic or noncancer BE mucosa with intestinal metaplasia using endoscopic FFPE samples.     

Transanal ultrasound and manometry in the evaluation of fecal incontinence

PURPOSE: This preliminary study was undertaken to clarify the role of ultrasonography of anal sphincters in the colorectal laboratory. METHODS: Twenty-eight parous female patients with fecal incontinence were evaluated with transanal ultrasonography (TAUS), anal manometry, and pudendal nerve terminal motor latency (PNTML). Ultrasound images were recorded and labeled in centimeters from the anal verge. The continuity of the internal anal sphincter (IAS) was identified as either intact or disrupted. The separation of the external anal sphincter (EAS) was measured at the 1.5-cm level and below. TAUS findings were then compared with anal manometric pressures. Clinical data were obtained by patient interview and examination during TAUS. RESULTS: Evidence of IAS disruption was associated with significantly decreased mean maximum resting pressures (P=0.023). EAS separation was inversely proportional to mean maximum squeezing pressures (r=?0.61). In the group of patients offered sphincteroplasty, the IAS was disrupted more often (P=0.016), mean maximum resting pressures were significantly lower (P=0.023), mean EAS separation was significantly greater (P=0.022), and mean PNTML was significantly faster (P=0.004). Twenty-five percent of patients with normal clinical examinations had significant muscular injury by TAUS requiring sphincteroplasty. CONCLUSIONS: Manometric findings correlate significantly with anal sphincter defects visualized by TAUS. TAUS is useful in the evaluation and management of patients with fecal incontinence.     

Prognostic significance of right ventricular infarction diagnosed by ST elevation in right chest leads V3R to V7R

The prognostic significance of electrocardiographic "extensive right ventricular infarction" diagnosed by ST elevation greater than or equal to 1 mm in right chest leads V3R to V7R during inferior/posterior infarction was evaluated in 158 consecutive patients with first anterior (n = 72) or inferior/posterior (n = 86) myocardial infarction. At follow-up the maximum observation time was 3.0 years (mean 1.8 years). A total of 49 patients died; 96% due to cardiac causes. Twelve patients (8%) died during the first 24 hours of admission. Ten-day mortality was 18% (n = 29). Using Cox multivariate analysis ST elevation in right chest leads during inferior/posterior infarction was an independent predictor of prognosis in patients surviving the initial 10 days after infarction (n = 129). For these patients the cumulative survival was better after inferior/posterior infarction with ST elevation in V3R to V7R (n = 25) compared with (1) inferior/posterior infarction without St elevation in these leads (n = 45, P = 0.09), (2) anterior infarction (n = 59, P = 0.08), and (3) all other infarctions (n = 104, P = 0.05). Infarct size estimated by the peak serum enzyme values was similar in these groups. Thus, electrocardiographic extensive right ventricular infarction predicts a good prognosis in patients alive 10 days after infarction. Compared with infarcts of similar size but with another location the prognosis is better, probably due to concomitant smaller left ventricular infarction with better left ventricular function following infarction.