Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy

1 Background and aims

Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long‐term outcomes of upgrading from pacemakers to CRT with (CRT‐D) or without (CRT‐P) defibrillation in patients with no history of sustained ventricular arrhythmias.

2 Methods and results

In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT‐P or CRT‐D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4–7.0]. In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10–1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05–1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96–1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36–0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34–0.79), and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40–0.82) were lower after CRT‐D than after CRT‐P.

3 Conclusion

Upgrading from pacemakers to CRT was associated with a similar long‐term risk of mortality and morbidity to de novo CRT. After upgrade, CRT‐D was associated with a lower mortality than CRT‐P.     

Effect of cardiopulmonary bypass on cytochrome P450 enzyme activity: implications for pharmacotherapy

For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug–drug interactions. Clinically significant changes in drug PK during CPB are likely to be prominent for drugs where CYP metabolism is a major clearance (CL) mechanism. However, clinical data from patients undergoing CPB surgery in support of this hypothesis are lacking, leaving a significant knowledge gap. In this review, we address the effects of CPB on the release of pro-inflammatory cytokines, in surgeries with and without CPB, both pre and post initiation of surgery. We reviewed literature to explore the relationship between the release of pro-inflammatory cytokines, and the expression and activities of CYP enzymes. Through this approach, we provide new insight on the effects of CPB on the PK of drugs administered to patients in the clinical setting. Future research to address this knowledge gap will have considerable impact to assist clinicians with optimizing pharmacotherapy in this patient population.     

Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear Implantation

To test whether there are variations in cochlear orientation with respect to age and sex, and its relevance in cochlear implant surgery. Implant otologists rely upon the anatomic landmarks including the facial recess and round window niche and round window membrane for accessibility and placement of electrode array into scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in cochlear orientation with respect to age. Cochlear orientation studied radiologically by pre-operative CT scan of temporal bone can guide a Surgeon’s approach to cochlear implantation. To investigate the changes in cochlear orientation with respect to age and sex; and its relevance in cochlear implantation. A retrospective analytical study was performed on CT scans of temporal bones in patients (of our hospital from July 2013 to January 2015 i.e. for a period of 18 months) with no congenital or radiological abnormalities of cochlea. The basal turn angulations of cochlea varied with age and majority of change occurred during early age. The basal turn angulations of cochlea in difficult situations during cochlear implantation were correlated with the data. There is a significant variation in cochlear orientation as measured radiologically by basal turn angulations relative to midsagittal plane. The more obtuse and acute basal turn angulations have implications like difficulty in cochleostomy and electrode placement during cochlear implantation.     

Optimal chest compression in cardiopulmonary resuscitation depends upon thoracic and back support stiffness

A biomechanical analysis of the constant peak displacement and constant peak force methods of cardiopulmonary resuscitation (CPR) has revealed that optimal CC performance strongly depends on back support stiffness, CC rate, and the thoracic stiffness of the patient being resuscitated. Clinically the results presented in this study suggest that the stiffness of the back support surfaces found in many hospitals may be sub-optimal and that a backboard or a concrete floor can be used to enhance CC effectiveness. In addition, the choice of optimal CC rate and maximum sternal force applied by clinicians during peak force CPR is ought to be based on a general assessment of the patient??s thoracic stiffness, taking into account the patient??s age, gender, and physical condition; which is consistent with current clinical practice. In addition, it is important for clinicians to note that very high peak sternal forces, exceeding the limit above which severe chest wall trauma and abdominal injury occurs, may be required for optimal CC during peak force CPR on patients with very stiff chests. In these cases an alternative CPR technique may be more appropriate.     

Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

Proteasome inhibition (PI) has been reported to interfere with antibody‐driven autoimmune diseases. The impact of PI on the allergic immune response and on skin diseases like atopic dermatitis (AD) has not been thoroughly explored, however. Here, we examined whether the PI bortezomib interferes with the allergic immune response and the severity of AD by using an established mouse model of allergen‐driven dermatitis, to which bortezomib was applied after the establishment of systemic sensitization to ovalbumin. The treatment indeed resulted in a remarkable decrease in total and allergen‐specific plasma cells/antibody‐secreting cells, as evidenced by flow cytometry and ELISpot, respectively. This was accompanied by rapid reductions in serum antibody titres, including a prominent reduction of the IgE isotype. CD4+ and CD8+ cells were greatly diminished in lesional skin on immunohistological staining. The impressive effects at the level of immune modulation did not result in any improvement in the eczema, however. Following up on this unexpected result, we found that the skin itself was susceptible to bortezomib, by which it was instructed to lower the expression of critical skin barrier genes, especially transglutaminase‐1 and filaggrin. Together, bortezomib eliminates plasma cells and decreases immunoglobulin responses, including allergenic IgE. Although anti‐inflammatory effects are detectable in the skin, counter‐regulatory effects from PI on resident skin cells likely undermine improvement in the eczema. These results caution against the therapeutic use of bortezomib for inflammatory skin disorders, which are characterized by inherently impaired barrier function, especially AD.     

Evaluating components of dental care utilization among adults with diabetes and matched controls via hurdle models

Background

About one-third of adults with diabetes have severe oral complications. However, limited previous research has investigated dental care utilization associated with diabetes. This project had two purposes: to develop a methodology to estimate dental care utilization using claims data and to use this methodology to compare utilization of dental care between adults with and without diabetes.

Methods

Data included secondary enrollment and demographic data from Washington Dental Service (WDS) and Group Health Cooperative (GH), clinical data from GH, and dental-utilization data from WDS claims during 2002–2006. Dental and medical records from WDS and GH were linked for enrolees continuously and dually insured during the study. We employed hurdle models in a quasi-experimental setting to assess differences between adults with and without diabetes in 5-year cumulative utilization of dental services. Propensity score matching adjusted for differences in baseline covariates between the two groups.

Results

We found that adults with diabetes had lower odds of visiting a dentist (OR = 0.74, p < 0.001). Among those with a dental visit, diabetes patients had lower odds of receiving prophylaxes (OR = 0.77), fillings (OR = 0.80) and crowns (OR = 0.84) (p <  0.005 for all) and higher odds of receiving periodontal maintenance (OR = 1.24), non-surgical periodontal procedures (OR = 1.30), extractions (OR = 1.38) and removable prosthetics (OR = 1.36) (p < 0.001 for all).

Conclusions

Patients with diabetes are less likely to use dental services. Those who do are less likely to use preventive care and more likely to receive periodontal care and tooth-extractions. Future research should address the possible effectiveness of additional prevention in reducing subsequent severe oral disease in patients with diabetes.

     

Transient global amnesia during a professional cello concert

Transient global amnesia (TGA) is a great curiosity in medicine, the underlying pathophysiology of which remains under debate. When an episode occurs during the performance of a task requiring refined technical skills and an intense level of concentration such as a musical performance, it draws attention to the relationship between memory and performance. It also raises questions of access to procedural memory and other aspects of stored information. We encountered a renowned and highly proficient musician who was amnestic for a challenging concert.     

Can neuroimaging help aphasia researchers? Addressing generalizability,variability, and interpretability

Neuroimaging studies of individuals with brain damage seek to link brain structure and activity to cognitive impairments, spontaneous recovery, or treatment outcomes. To date, such studies have relied on the critical assumption that a given anatomical landmark corresponds to the same functional unit(s) across individuals. However, this assumption is fallacious even across neurologically healthy individuals. Here, we discuss the severe implications of this issue, and argue for an approach that circumvents it, whereby: (i) functional brain regions are defined separately for each subject using fMRI, allowing for inter-individual variability in their precise location; (ii) the response profile of these subject-specific regions are characterized using various other tasks; and (iii) the results are averaged across individuals, guaranteeing generalizabliity. This method harnesses the complementary strengths of single-case studies and group studies, and it eliminates the need for post hoc “reverse inference” from anatomical landmarks back to cognitive operations, thus improving data interpretability.