Outcomes of Cardiac Resynchronization Therapy by New York Heart Association Class: A Patient-Level Meta-Analysis.

Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure (HF) symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory NYHA IV vs. III functional class at the time of device implantation. In this meta-analysis, we pooled patient-level data from the MIRACLE, MIRACLE-ICD, and COMPANION trials. Outcomes evaluated were time to the composite endpoint of first HF hospitalization (HFH) or all-cause mortality and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian Hierarchical Weibull survival regression model. We assessed if this association differs between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from the RAFT trial. Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to HFH or all-cause mortality (adjusted hazard ratio [aHR] 0.79, 95%CI 0.64 - 0.99, p = 0.044), with a similar association with time to all-cause mortality (aHR 0.78, 95% CI 0.59 - 1.03, p = 0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR 0.72, 95% CI 0.30 - 1.27, p = 0.23 for HFH/mortality; ratio of aHR 0.70, 95% CI 0.35 - 1.34, p = 0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Physical examination techniques for the assessment of pelvic floor myofascial pain: a systematic review.

BACKGROUND: Myofascial pain is characterized by the presence of trigger points, tenderness to palpation, and local or referred pain, and commonly involves the pelvic floor muscles in men and women. Pelvic floor myofascial pain in the absence of local or referred pain has also been observed in patients with lower urinary tract symptoms, and we have found that many patients report an improvement in these symptoms after receiving myofascial-targeted pelvic floor physical therapy. OBJECTIVE: We sought to systematically review the literature for examination techniques used to assess pelvic floor myofascial pain in women. STUDY DESIGN: We performed a systematic literature search using strategies for the concepts of pelvic floor disorders, myofascial pain, and diagnosis in Ovid MEDLINE 1946-, Embase 1947-, Scopus 1960-, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Cochrane Database of Systematic Reviews. Articles were screened by 3 authors and included if they contained a description of a pelvic myofascial physical examination. RESULTS: In all, 55 studies met our inclusion criteria. Overall, examination components varied significantly among the included studies and were frequently undefined. A consensus examination guideline was developed based on the available data and includes use of a single digit (62%, 34/55) to perform transvaginal palpation (75%, 41/55) of the levator ani (87%, 48/55) and obturator internus (45%, 25/55) muscles with a patient-reported scale to assess the level of pain to palpation (51%, 28/55). CONCLUSION: Physical examination methods to evaluate pelvic musculature for presence of myofascial pain varied significantly and were often undefined. Given the known role of pelvic floor myofascial pain in chronic pelvic pain and link between pelvic floor myofascial pain and lower urinary tract symptoms, physicians should be trained to evaluate for pelvic floor myofascial pain as part of their physical examination in patients presenting with these symptoms. Therefore, the development and standardization of a reliable and reproducible examination is needed.

Assessing the Utility of a Novel SMS- and Phone-Based System for Blood Pressure Control in Hypertensive Patients: Feasibility Study.

BACKGROUND: Although hypertension (HTN) is a major modifiable risk factor for arterial damage, blood pressure (BP) remains poorly controlled in the hypertensive population. Telemedicine is a promising adjunct intervention that may complement traditional therapies and improve adherence rates; however, current approaches have multiple barriers to entry, including the use of relatively expensive Bluetooth devices or the dependence on smart phone utilization, which tend to exclude low-income and more elderly populations. OBJECTIVE: The aim of this study was to design and implement a new phone call- and short message service text messaging-based intervention, Epharmix's EpxHypertension, in a quality improvement project that demonstrates the feasibility of this system for BP control in a family medicine setting. METHODS: We recruited 174 patients from a community clinic in St Louis from a database of patients diagnosed with HTN. An automated call or text messaging system was used to monitor patient-reported BPs. If determined to be elevated, physicians were notified by an email, text, or electronic medical record alert. Mean systolic BPs (SBPs) and diastolic BPs (DBPs) were compared at the beginning and end of 12 weeks. RESULTS: After 12 weeks on the system, patients with a baseline SBP of 140 mm Hg or higher reduced SBP by 10.8 mm Hg (95% CI -14.5 to -7.2, P<.001) and DBP by 6.6 mm Hg (95% CI -9.9 to -3.4, P=.002), but no significant changes were observed in overall BPs and BPs in the group with baseline SBP less than 140 mm Hg. CONCLUSIONS: EpxHypertension provides a viable means to control HTN in patients with high baseline BPs despite previous therapy. This community implementation study demonstrates the feasibility of implementing EpxHypertension across a primary care setting without the need for smartphones or Bluetooth-linked BP cuffs. Future studies should evaluate its effectiveness in a randomized control trial compared with standard of care.

Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements.

Epigenome editing with the CRISPR (clustered, regularly interspaced, short palindromic repeats)-Cas9 platform is a promising technology for modulating gene expression to direct cell phenotype and to dissect the causal epigenetic mechanisms of gene regulation. Fusions of nuclease-inactive dCas9 to the Krüppel-associated box (KRAB) repressor (dCas9-KRAB) can silence target gene expression, but the genome-wide specificity and the extent of heterochromatin formation catalyzed by dCas9-KRAB are not known. We targeted dCas9-KRAB to the HS2 enhancer, a distal regulatory element that orchestrates the expression of multiple globin genes, and observed highly specific induction of H3K9 trimethylation (H3K9me3) at the enhancer and decreased chromatin accessibility of both the enhancer and its promoter targets. Targeted epigenetic modification of HS2 silenced the expression of multiple globin genes, with minimal off-target changes in global gene expression. These results demonstrate that repression mediated by dCas9-KRAB is sufficiently specific to disrupt the activity of individual enhancers via local modification of the epigenome.