Antibiotic‐induced Cardiac Arrhythmias

This review aims to clarify the underlying risk of arrhythmia associated with the use of macrolides and fluoroquinolones antibiotics. Torsades de pointes (TdP) is a rare potential side effect of fluoroquinolones and macrolide antibiotics. However, the widespread use of these antibiotics compounds the problem. These antibiotics prolong the phase 3 of the action potential and cause early after depolarization and dispersion of repolarization that precipitate TdP. The potency of these drugs, as potassium channel blockers, is very low, and differences between them are minimal. Underlying impaired cardiac repolarization is a prerequisite for arrhythmia induction. Impaired cardiac repolarization can be congenital in the young or acquired in adults. The most important risk factors are a prolonged baseline QTc interval or a combination with class III antiarrhythmic drugs. Modifiable risk factors, including hypokalemia, hypomagnesemia, drug interactions, and bradycardia, should be corrected. In the absence of a major risk factor, the incidence of TdP is very low. The use of these drugs in the appropriate settings of infection should not be altered because of the rare risk of TdP, except among cases with high‐risk factors.     

Accurate de novo structure prediction of large transmembrane protein domains using fragment-assembly and correlated mutation analysis

A new de novo protein structure prediction method for transmembrane proteins (FILM3) is described that is able to accurately predict the structures of large membrane proteins domains using an ensemble of two secondary structure prediction methods to guide fragment selection in combination with a scoring function based solely on correlated mutations detected in multiple sequence alignments. This approach has been validated by generating models for 28 membrane proteins with a diverse range of complex topologies and an average length of over 300 residues with results showing that TM-scores > 0.5 can be achieved in almost every case following refinement using MODELLER. In one of the most impressive results, a model of mitochondrial cytochrome c oxidase polypeptide I was obtained with a TM-score > 0.75 and an rmsd of only 5.7 Å over all 514 residues. These results suggest that FILM3 could be applicable to a wide range of transmembrane proteins of as-yet-unknown 3D structure given sufficient homologous sequences.     

Renal infarction as a presentation of austrian syndrome: thromboembolic phenomenon of pneumococcal endocarditis

ABSTRACT:: A 52-year-old unvaccinated and splenectomized man presented with fever, altered sensorium, bilateral flank pain and chest discomfort accompanied with paroxysmal atrial fibrillation with a rapid ventricular response. An abdominal computed tomography scan was performed, which revealed a right renal infarct and splenosis. Transthoracic echocardiography was performed, which demonstrated an echodense structure on the mitral valve with mitral regurgitation and a vegetation on the aortic valve with aortic regurgitation. Subsequently, he was found to have pneumococcal infective endocarditis, pneumococcal pneumonia and bacterial meningitis, namely Austrian syndrome. He underwent an early aortic valve and mitral valve repair but still had a poor clinical outcome. Renal infarction has a mortality of approximately 13.2%, which is strongly influenced by the underlying diseases and infectious complications. Medical and surgical treatment initiated in a timely manner is often inadequate. The authors report the first case of Austrian syndrome presenting with renal infarction as a clue to an embolic event associated with infective endocarditis in this study.     

Development and evaluation of a simulator-based laparoscopic training program for surgical novices

Background

The use of simulation to train novice surgeons in laparoscopic skills is becoming increasingly popular. To maximize benefit from simulation, training needs to be delivered and assessed in a structured manner. This study aimed to define performance goals, demonstrate construct validity of the training program, and evaluate whether novice surgeons could reach the preset performance goals.

Methods

Nine expert laparoscopic surgeons established performance goals for three basic modules of an augmented-reality laparoscopic simulator. The three laparoscopic modules were used by 40 novice surgeons and 40 surgical trainees (postgraduate years [PGYs] 1–4). The performance outcomes were analyzed across the different groups (novice, PGYs 1 and 2, PGYs 3 and 4, expert) to determine construct validity. Then 26 recruited novices trained on the three modules with the aim of reaching the performance goals.

Results

The results demonstrated a significant difference in performance between all levels of experience for time (p < 0.001), motion analysis (p < 0.001), and error score (p < 0.001), thus demonstrating construct validity. All 26 novice surgeons significantly improved in performance with repetition for the metrics of time (p < 0.001) and motion analysis (p < 0.001). For two of the modules, the proficiency goals were reached in fewer than 10 trials by 80 % of the study participants.

Conclusion

Basic skills in laparoscopic surgery can be learned and improved using proficiency-based simulation training. It is possible for novice surgeons to achieve predefined performance goals in a reasonable time frame.     

Parental posttraumatic stress symptoms as a moderator of child's acute biological response and subsequent posttraumatic stress symptoms in pediatric injury patients

OBJECTIVE: To examine how parental responses following pediatric injury may influence their child's posttraumatic stress symptoms (PTSS). METHODS: Heart rate (HR) from 82 pediatric injury patients was measured during emergency medical services (EMSs) transport and following hospital admission. Twelve-hour urinary cortisol levels were assessed upon admission. Child PTSS and parental PTSS and general distress were assessed 6 weeks and 6 months after trauma. RESULTS: Six-week parental PTSS predicted 6-month child PTSS even after controlling for demographics and general parent distress (DeltaR(2) = .08, p = .03). Parental PTSS moderated the relationship between (a) child cortisol levels and 6-month child PTSS (DeltaR2 = .08, p = .03) and between (b) hospital HR and 6-month child PTSS (DeltaR2 = .09, p = .03). CONCLUSION: The present findings suggest that parental response to trauma may interact with child acute physiological responses to predict persistent child PTSS.     

Development and psychometric evaluation of the patient knowledge of,and attitudes and behaviours towards pressure ulcer prevention instrument (KPUP)

The Patient Knowledge of, and Attitude and Behaviour towards Pressure Ulcer Prevention Instrument (KPUP) was developed and validated using a two‐stage prospective psychometric instrument validation study design. In Stage 1, the instrument was designed, and it is psychometrically evaluated in Stage 2. To establish content validity, two expert panels independently reviewed each item for appropriateness and relevance. Psychometric evaluation included construct validity and stability testing of the instrument. The questionnaire was administered to a convenience sample of 200 people aged more than 65 years, living independently in the community; reliability and stability were assessed by test/retest procedures, with a 1‐week interval. Mean knowledge scores at ‘test’ were 11.54/20 (95% CI = 11.10‐11.99, SD: 3.07), and ‘retest’ was 12.24 (95% CI = 11.81‐12.66, SD: 2.93). For knowledge, correlation between the test/retest score was positive (r=. 60), attitude section‐inter‐item correlations ranged from r = −.31 to r = .57 (mean intraclass correlation coefficient of r = .42), and internal consistency for the retest was the same as the test (α = .41 for the eight items). For health behaviours, individual inter‐item correlations for test items ranged from r = −.21 to r = .41 for the 13 standardised items. Psychometric testing of the KPUP in a sample of older persons in the community provided moderate internal consistency and general high test‐retest stability.     

Meta-Analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder

The hypothalamic-pituitary-adrenal (HPA) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (PTSD). Although numerous HPA-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. To address these inconsistencies in the PTSD candidate gene literature, we conducted meta-analyses of HPA-related genes from both a traditional single nucleotide polymorphism (SNP)–level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. Database searches (PubMed and PsycINFO) identified 24 unique articles examining six HPA-axis genes in PTSD; analyses were conducted on four genes (ADCYAP1R1, CRHR1, FKBP5, NR3C1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, PTSD as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. Findings from SNP-level analyses indicated that two variants (rs9296158 in FKBP5 and rs258747 in NR3C1) were nominally associated with PTSD, ps = .001 and .001, respectively, following multiple testing correction. At the gene level, significant relations between PTSD and both NR3C1 and FKBP5 were detected and robust to sensitivity analyses. Although study limitations exist (e.g., varied outcomes, inability to test moderators), taken together, these results provide support for FKBP5 and NR3C1 in risk for PTSD. Overall, this work highlights the utility of meta-analyses in resolving discrepancies in the literature and the value of adopting gene-level approaches to investigate the etiology of PTSD.