Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome.

CONTEXT: Fatal arrhythmias from occult long QT syndrome may be responsible for some cases of sudden infant death syndrome (SIDS). Because patients who have long QT syndrome with sodium channel gene (SCN5A) defects have an increased frequency of cardiac events during sleep, and a recent case is reported of a sporadic SCN5A mutation in an infant with near SIDS, SCN5A has emerged as the leading candidate ion channel gene for SIDS. OBJECTIVE: To determine the prevalence and functional properties of SCN5A mutations in SIDS. DESIGN, SETTING, AND SUBJECTS: Postmortem molecular analysis of 93 cases of SIDS or undetermined infant death identified by the Medical Examiner's Office of the Arkansas State Crime Laboratory between September 1997 and August 1999. Genomic DNA was extracted from frozen myocardium and subjected to SCN5A mutational analyses. Missense mutations were incorporated into the human heart sodium channel alpha subunit by mutagenesis, transiently transfected into human embryonic kidney cells, and characterized electrophysiologically. MAIN OUTCOME MEASURES: Molecular and functional characterization of SCN5A defects. RESULTS: Two of the 93 cases of SIDS possessed SCN5A mutations: a 6-week-old white male with an A997S missense mutation in exon 17 and a 1-month old white male with an R1826H mutation in exon 28. These 2 distinct mutations occurred in highly conserved regions of the sodium channel and were absent in 400 control patients (800 alleles). Functionally, the A997S and R1826H mutant channels expressed a sodium current characterized by slower decay and a 2- to 3-fold increase in late sodium current. CONCLUSION: Approximately 2% of this prospective, population-based cohort of SIDS cases had an identifiable SCN5A channel defect, suggesting that mutations in cardiac ion channels may provide a lethal arrhythmogenic substrate in some infants at risk for SIDS.     

Updates on bacterial resistance and empirical antibiotics treatment of complicated acute appendicitis in children

Objective: Through historical comparison with our previous study published 10 years ago, this paper aims to provide latest analysis of local bacteriology of acute complicated appendicitis and evaluate the effects of early escalation of potent antibiotics on course of postoperative recovery.Methods: A 5-year retrospective review of all children receiving emergency laparoscopic appendicectomies for acute appendicitis from December 2014 to November 2019 was conducted.Results: 257 cases of acute appendicitis were included, 126 were complicated appendicitis (38 gangrenous, 88 ruptured). 96 had positive peritoneal swab culture, 53 (42.1%) grew resistant bacterial strains, including extended spectrum beta-lactamase producing E. coli (ESBL E. coli), Pseudomonas aeruginosa, against traditional empirical triple antibiotics. The prevalence had significantly increased over the past decade (p = 0.008). In our patients, piperacillin/tazobactam, ertapenem, gentamicin provided coverage of 69.8%, 45.3% and 45.3% respectively. For patients with early escalation of postoperative antibiotics, no statistical significance was identified in terms of postoperative complications (p = 0.883), or duration of antibiotics (p = 0.0615).Conclusion: Growing prevalence of resistant strains were observed over the decade. Piperacillin/tazobactam provided the best coverage (69.8%) against resistant bacterial strains in our patients. Early escalation of antibiotics failed to reduce postoperative complications and antibiotics duration.Type of Study: Clinical Research, Retrospective Historical Comparative StudyLevel of Evidence: Level III     

Emergency surgery comparison of right versus left acute colonic diverticulitis: A 10-year outcome analysis

IntroductionThe difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery.MethodWe conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated.ResultsIn total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6).ConclusionRight colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease.     

A Multilevel Intervention to Increase HPV Vaccination among Asian American Adolescents

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US. HPV vaccine is a viable source of prevention against high-risk strains that are likely to cause cancer. However, particularly among racial and ethnic minorities such as Chinese Americans, HPV vaccination rates are suboptimal. The goal of this study was to evaluate the effect of a culturally tailored intervention on HPV vaccine uptake in Chinese Americans. We designed and implemented a multilevel longitudinal pilot study to examine the efficacy of the HPV intervention among Chinese American parents/guardians. We recruited 180 participants from federally qualified health center and community-based clinics that serve predominantly low-income Chinese Americans in Philadelphia. Participants were randomized into an intervention group (n?=?110) or a control group (n?=?70). The intervention group received an HPV specific intervention, while the control group received a general health intervention. The primary outcome was medical record-confirmed receipt of first shot and completion of HPV vaccine within six months of receiving the interventions. Repeated measure ANOVA was utilized to examine the intervention effect on knowledge between intervention and control groups. Knowledge differed significantly, with participants in the intervention group demonstrating the greatest improvement following the intervention. A multivariable logistic regression was used to examine the association between HPV vaccine initiation and study group assignment. There was a significant effect of provider recommendation, parent’s gender, and health insurance status on HPV vaccine uptake. This study demonstrated positive impact of a culturally tailored intervention on HPV vaccination uptake among Chinese Americans.

     

Liver transplantation: would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion?

BackgroundHepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain.MethodsA propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed.ResultsA consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively).ConclusionsLT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered.     

Meta-analytic methods for health services research--an example from geriatrics

The authors recently published a meta-analysis of controlled trials of comprehensive geriatric assessment (CGA). The results supported the view that efficacy of CGA is strongly related to the patients, objectives, and basic design of CGA programs, and that particular program models and design features are associated with important health outcome improvements (e.g., survival, living at home, and functional improvement at follow-up). Present objectives include the outline of methods and how they were developed given the condition of the trial database and scientific context. Aspects of the approach, such as (a) survey of primary trialists to recover unpublished information and standardize data, (b) development of a program typology to guide the principal analysis, and (c) incorporation of program design features as covariates where statistical heterogeneity was detected, proved extremely useful, and have implications for other systematic reviews of similarly complex primary trials of new health care technologies, health services, and organizational interventions.     

Prior topical anesthesia reduces time to full cycloplegia in Chinese

PURPOSE: To investigate the effect of prior anesthesia on the time to full cycloplegia in young Chinese subjects. METHODS: The amplitude of accommodation was monitored over a 50-minute interval after the application of 1% cyclopentolate hydrochloride with a pretreatment of 0.4% benoxinate (oxybuprocaine) or 0.9% saline solution (control). Using a nonlinear mathematical model, the rate of accommodative loss (k) and the time required for 95% of total cycloplegia (T95%) were determined. RESULTS: Statistical analysis revealed a significantly faster rate of accommodative loss (P < .0001) after prior anesthesia (0.129 +/- 0.05) compared with the controls (0.103 +/- 0.04). T95% was noted at 26.43 +/- 10.22 minutes after prior anesthesia, which was significantly shorter (P < .0001) than that after the saline treatment (35.28 +/- 16.51 minutes). CONCLUSIONS: Prior application of topical anesthetic can shorten the time to full cycloplegia for people, such as the Chinese, with dark irides.     

Laparoscopic-assisted colorectal surgery

PURPOSE: To audit the development and outcomes of laparoscopic colorectal surgery at the Royal Brisbane Hospital. METHODS: Since July 1991, laparoscopic-assisted colectomy for benign and malignant colorectal disease has been performed on more than 300 patients at the Royal Brisbane Hospital. This paper summarizes the outcome for the first 240 patients who underwent a laparoscopic colorectal procedure. All laparoscopic data were collected prospectively, and for selected studies, data were compared with open surgical controls. RESULTS: Nineteen patients required open conversion (7.9 percent). There was a significant decrease in wound infection rates in patients having a laparoscopic-assisted colectomy (3.6 percent) compared with historical controls (7.9 percent) (P<0.05; chisquared). There were five anastomotic leaks, five laparotomies for postoperative adhesive obstruction, and four perioperative deaths. A total of 103 patients had a procedure for colorectal cancer. Of the 79 potentially curative procedures, there have been 5 (6.3 percent) recurrences to date. CONCLUSION: The overall morbidity and mortality in this series seem to be acceptable compared with that of open procedures.     

Academic quality improvement: new medicine in old bottles

Academic medical centers and clinicians have been slow to embrace continuous quality improvement. The Mount Sinai Medical Center in New York has created a new Department of Health Policy that combines an academic research mission with an administrative mission to demonstrate improving quality of care. This article discusses the conceptual framework that undergirds this new effort, its organizational structure and initial agenda of activities, and why we believe it will succeed in engaging academic physicians in quality improvement.