Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

Background: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac events.
Methods and Results: The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage-gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0–0.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470–0.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P <0.001) and aborted cardiac arrest/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta-blocker therapy.
Conclusions: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta-blocker therapy.     

Laparoscopic Hernia Repair of an Incisional Hernia Secondary to Placement of an Implantable Cardioverter Defibrillator

We present the lapamscopic repair of a large incisional hernia secondary to placement of a subcostal ICD pulse generator. Laparoscopic repair of large incisional hernias provides a unique and technically feasible form of repair in the 2%–13% of patients who will develop an incisional hernia following an abdominal surgery. This form of hernia repair is associated with minimal morbidity and prompt resumption of patient activities and work.     

Unilateral groin surgery in children: will the addition of an ultrasound‐guided ilioinguinal nerve block enhance the duration of analgesia of a single‐shot caudal block?

Background: Inguinal hernia repair, hydrocelectomy, and orchidopexy are commonly performed surgical procedures in children. Postoperative pain control is usually provided with a single‐shot caudal block. Blockade of the ilioinguinal nerve may lead to additional analgesia. The aim of this double‐blind, randomized controlled trial was to evaluate the efficacy of an adjuvant blockade of the ilioinguinal nerve using ultrasound (US) guidance at the end of the procedure with local anesthetic vs normal saline and to explore the potential for prolongation of analgesia with decreased need for postoperative pain medication. Methods: Fifty children ages 1–6 years scheduled for unilateral inguinal hernia repair, hydrocelectomy, orchidopexy, or orchiectomy were prospectively randomized into one of two groups: Group S that received an US‐guided ilioinguinal nerve block with 0.1 ml·kg^?1 of preservative‐free normal saline and Group B that received an US‐guided nerve block with 0.1 ml·kg^?1 of 0.25% bupivacaine with 1 : 200 000 epinephrine at the conclusion of the surgery. After induction of anesthesia but prior to surgical incision, all patients received caudal anesthesia with 0.7 ml·kg^?1 of 0.125% bupivacaine with 1 : 200 000 epinephrine. Patients were observed by a blinded observer for (i) pain scores using the Children and Infants Postoperative Pain Scale, (ii) need for rescue medication in the PACU, (iii) need for oral pain medications given by the parents at home. Results: Forty‐eight patients, consisting of 46 males and two females, with a mean age of 3.98 (sd ± 1.88) were enrolled in the study. Two patients were excluded from the study because of study protocol violation and/or alteration in surgical procedure. The average pain scores reported for the entire duration spent in the recovery room for the caudal and caudal/ilioinguinal block groups were 1.92 (sd ± 1.59) and 1.18 (sd ± 1.31), respectively. The average pain score difference was 0.72 (sd ± 0.58) and was statistically significant (P < 0.05). In addition, when examined by procedure type, it was found that the difference in the average pain scores between the caudal and caudal/ilioinguinal block groups was statistically significant for the inguinal hernia repair patients (P < 0.05) but not for the other groin surgery patients (P = 0.13). For all groin surgery patients, six of the 23 patients in the caudal group and eight of the 25 patients in the caudal/ilioinguinal block group required pain rescue medications throughout their entire hospital stay or at home (P = 0.76). Overall, the caudal group received an average of 0.54 (sd ± 1.14) pain rescue medication doses, while the caudal/ilioinguinal block group received an average of 0.77 (sd ± 1.70) pain rescue medication doses; this was, however, not statistically significant (P = 0.58). Conclusions: The addition of an US‐guided ilioinguinal nerve block to a single‐shot caudal block decreases the severity of pain experienced by pediatric groin surgery patients. The decrease in pain scores were particularly pronounced in inguinal hernia repair patients.     

Innovative Legal Approaches to Address Obesity

Context: The law is a powerful public health tool with considerable potential to address the obesity issue. Scientific advances, gaps in the current regulatory environment, and new ways of conceptualizing rights and responsibilities offer a foundation for legal innovation.
Methods: This article connects developments in public health and nutrition with legal advances to define promising avenues for preventing obesity through the application of the law.
Findings: Two sets of approaches are defined: (1) direct application of the law to factors known to contribute to obesity and (2) original and innovative legal solutions that address the weak regulatory stance of government and the ineffectiveness of existing policies used to control obesity. Specific legal strategies are discussed for limiting children's food marketing, confronting the potential addictive properties of food, compelling industry speech, increasing government speech, regulating conduct, using tort litigation, applying nuisance law as a litigation strategy, and considering performance-based regulation as an alternative to typical regulatory actions. Finally, preemption is an overriding issue and can play both a facilitative and a hindering role in obesity policy.
Conclusions: Legal solutions are immediately available to the government to address obesity and should be considered at the federal, state, and local levels. New and innovative legal solutions represent opportunities to take the law in creative directions and to link legal, nutrition, and public health communities in constructive ways.     

Is The Australian National Heart Foundation programme effective in reducing cholesterol levels among general practice patients?

Despite the contribution of elevated cholesterol to the developmentof cardiovascular disease, many individuals continue to havecholesterol levels greater than the 5.5 mmol/l recommended bythe Australian National Heart foundation (NHF). Although generalpractitioners appear to be well placed to offer dietary adviceto help patients to reduce their cholesterol levels, there havebeen few if any randomised trials evaluating the effectivenessof general practitioners in this area. A randomised trial ofthe relative effectiveness of two general practitioner programmesin reducing cholesterol levels among patients with cholesterollevels between 5.5 and 7.9 mmol/l was undertaken. The dietaryadvice programme developed by the NHF for use by general practitionerswas compared with minimal advice (feedback on cholesterol level,pamphlet and warning of follow-up). Serum cholesterol was measuredusing a portable Reflotron. At 4-month follow-up, the patientsin the NHF group (n=76) had significantly greater reductionsin cholesterol levels than those in the minimal group (n=70),and a greater proportion of NHF patients had reduced their cholesterolbelow risk levels. On average, the patients in the NHF groupreduced their cholesterol by 0.84 mmol/l or 13.5% of baselinelevels. There were no differences between the NHF and minimalgroup on changes in pre-to post-test body mass index, attitudesor self-reported dietary change and only minimal differencesin satisfaction with advice received.     

An Esophageal and Gastric Approach to Ventricular Pacing

Using a unipolar esothoracic pacing system (where current passes from a point source positioned in the distal esophagus to a chest wall pad) and pulse duration of 50 msec, satisfactory 1:1 ventricular capture was obtained in57 (86%) of 66 patients, with a mean threshold current of 27.7 mA at an optimal depth of 40.3 cm from the lower lip. When the unipolar esothoracic and bipolar transesophageal ventricular pacing systems were compared, the bipolar system was associated with a lower success rate and higher threshold current. When unipolar esothoracic pacing and gastrothoracic pacing (where current passes from a point source positioned in the stomach to a chest wall pad) were compared in 23 patients with bradyarrhythmia, ventricular capture was achieved using gastrothoracic pacing in 22 patients (96%) and esothoracic pacing in 21 (91%): gastrothoracic pacing required less current (16.0 mA ± SD 7.2 vs25.8 mA± SD 8.6). Optimal ventricular capture occurred using a unipolar gastrothoracic pacing electrode inserted to an average depth of 44.3 cm together with a high impedance chest pad (250 Ω) placed in the fourth interspace at the left sternal edge, with 50-msec current pulses and a mean threshold of 16.0 mA. Thus, using a gastroesophageal electrode system, ventricular pacing can be achieved successfully, and the availability of such a system could play a major role in resuscitation of patients from severe bradyarrhythmias.     

A Gastroesophageal Electrode for Atrial and Ventricular Pacing

Temporary transvenous cardiac pacing requires technical expertise and access to fluoroscopy. We have developed a gastroesophageal electrode capable of atrial and ventricular pacing. The flexible polythene gastroesophageal electrode is passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus, are used for atrial pacing. A point source (cathode) on the distal tip of the electrode, now positioned in the gastric fundus. is used for ventricular pacing. Two configurations of atrial and ventricular pacing were compared: unipolar and bipolar. During unipolar ventricular pacing the indifferent electrode (anode) was a high impedance chest pad. For bipolar ventricular pacing the indifferent electrode was a ring electrode placed 2 cm proximal to the tip. Unipolar atrial pacing was performed with 1 of 5 proximal ring electrodes acting as cathode ("cathodic") or as anode ("anodic") in conjunction with a chest pad. Bipolar atrial pacing was performed using combinations of 2 of 5 ring electrodes. Atrial capture was obtained in all 55 subjects attempted. When all electrode combinations were compared, atrial capture was significantly more frequent using the bipolar approach (153/210 bipolar, 65/210 unipolar; t = 7.37, P < 0.001). For unipolar atrial pacing, cathodic stimulation (from esophagus) was more successful than anodic stimulation (cathodic 62/105, anodic 20/105; t = 5.81, P < 0.001). In 43 subjects attempted unipolar ventricular pacing resulted in a higher frequency of capture than the bipolar approach (unipolar 41/43 (95.3%), bipolar 19/43 (44.2%); P < 0.001). In conclusion, atrial pacing was optimal using pairs of ring electrodes ("bipolar") while ventricular pacing was optimal using the distal electrode tip (cathode) in conjunction with a chest pad electrode ("unipolar"). This gastroesophageal electrode may be useful in the emergency management of acute bradyarrhythmias and for elective electrophysiological studies.