Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach.

Introduction: eHealth seems promising in addressing challenges in the provision of care for Huntington's disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients' home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations. Methods: This article describes the qualitative human-centered design process and first evaluations of the Huntington Support App prototype: a web-app aimed to support the quality of life (QoL) of HDGECs and their partners in Europe. Prospective end-users, i.e., HDGECs, their partners, and healthcare providers (HCPs), from different countries were involved throughout the development process. Through interviews, we captured people's experiences with the disease, quality of life (QoL), and eHealth. We translated their stories into design directions that were further co-designed and subsequently evaluated with the user groups. Results: The resulting prototype centralizes clear and reliable information on the disease, HD-related news and events, as well as direct contact possibilities with HCPs via an online walk-in hour or by scheduling an appointment. The app's prototype was positively received and rated as (very) appealing, pleasant, easy to use and helpful by both HDGECs and partners. Discussion: By involving end-users in every step, we developed a healthcare app that meets relevant needs of individuals affected by HD and therefore may lead to high adoption and retention rates. As a result, the app provides low-threshold access to reliable information and specialized care for HD in Europe. A description of the Huntington Support App as well as implications for further development of the app's prototype are provided.

Quality of life, health-related quality of life, and associated factors in Huntington's disease: a systematic review.

BACKGROUND: Huntington's disease (HD) is a genetic, neurodegenerative disease. Due to the progressive nature of HD and the absence of a cure, (health-related) quality of life ((HR)QoL) is an important topic. Several studies have investigated (HR)QoL in HD, yet a clear synthesis of the existing literature is lacking to date. We performed a systematic review on self-reported (HR)QoL, and factors and intervention effects associated with (HR)QoL in premanifest and manifest HD gene expansion carriers (pHDGECs and mHDGECs, respectively). METHODS: PubMed, EMBASE, Web of Science, and PsycINFO were searched systematically from September 17th, 2021, up to August 11th, 2022. Methodological and conceptual quality of the included studies was assessed with two appraisal tools. RESULTS: 30 out of 70 eligible articles were included. mHDGECs experienced lower (HR)QoL compared to pHDGECs and controls, whereas mixed findings were reported when compared to other neurological diseases. Several factors were associated with (HR)QoL that might contribute to lower (HR)QoL in mHDGECs, including depressive symptoms, physical and psychological symptoms, lower functional capacity, lower support, and unmet needs. Multidisciplinary rehabilitation programs and a respiratory muscle training were beneficial for (HR)QoL in mHDGECs. DISCUSSION: (HR)QoL is experienced differently across the course of the disease. Although (HR)QoL is key for understanding the impact of HD and the effect of symptomatic treatment, there is a need to improve the methodological and conceptual shortcomings that were found in most studies, especially regarding the conceptual clarity when reporting on QoL and HRQoL. Suggestions for strengthening these shortcomings are provided in this review.

The Department of Anatomy in the University of the Philippines College of Medicine: Dissecting the history

@#The history of the Department of Anatomy of the College of Medicine of the University of the Philippines can be chronicled from its humble beginnings in 1907 to its continued existence through the COVID-19 pandemic. This article briefly describes its historical development, current undertakings, and future directions in relation to its mission and vision.

Clinicodemographic and computed tomography scan findings associated with thyroid gland invasion among patients with laryngeal squamous cell carcinoma

Objective@#We aim to determine the association between preoperative CT scan findings of thyroid cartilage invasion, cricoid cartilage invasion, and paraglottic space involvement with tumor extension to the thyroid gland on final histopathology among patients with laryngeal squamous cell carcinoma (SCC) in a tertiary hospital in the Philippines.@*Methods@#Patients with histopathologically-confirmed laryngeal SCC who underwent total laryngectomy with thyroidectomy while admitted at the public ward of the Department of Otorhinolaryngology, Philippine General Hospital, from January 2013 to December 2019 were included. CT scans were reviewed by 2 blinded independent radiologists. CT scan data including subsite/s involved, thyroid cartilage/cricoid cartilage erosion, paraglottic space involvement, thyroid gland involvement, and thyroid gland involvement on final histopathology were gathered. Clinicopathologic data such as age, T Stage, early tracheostomy, and time between CT scan and surgery were also collected and analyzed. Fisher’s exact test was computed for both clinicopathologic and CT scan data with a significant value having p<0.05. Cramer’s V and phi coefficient were computed for nondichotomous and dichotomous variables, respectively. Odds ratio was also computed for dichotomous variables with p<0.05 on Fisher’s exact test.@*Results@#Fifty-nine (59) men and 4 women were included, aged 43 to 81 years old. Most patients were classified as T3 (n=18) and T4 (n=41) (total=93.7%), with most having transglottic primary tumors (n=29, 46%), and only 8 (12.7%) patients having subglottic tumor involvement on final histopathology. Thyroid cartilage erosion or invasion were noted in 63.4% (n=40) of patients’ CT scans and 58.7% (n=37) of patients’ final histopathology reports. Cricoid cartilage and paraglottic space involvement were often not reported on final histopathology results. Thyroid gland involvement was only noted in the final histopathology reports of 5 patients (7.9%). Significant association between cricoid cartilage findings (p=0.032, Cramer’s V=0.318) or thyroid gland involvement on CT scan (p=0.018, Phi=0.384; OR 13 95% CI 1.797, 94.035) with thyroid gland involvement on final histopathology was noted. The rest of the variables had no significant association with thyroid gland involvement on final histopathology.@*Conclusion@#Cricoid cartilage involvement (erosion or invasion) and thyroid gland involvement on CT scan are associated with thyroid gland involvement on final histopathology in patients with laryngeal SCC. Patients with these CT scan findings may stand to benefit more from thyroidectomy to ensure good margins of resection.

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home. Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts. Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD.

Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFß signalling.

AIMS: Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFß) signalling pathway where inhibiting TGFß signalling maintains telomere length. The relationship between Pim1 and TGFß has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFß signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes. METHODS AND RESULTS: Telomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGFß signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGFß signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGFß pathway genes. CONCLUSION: Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGFß pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.

Clinicodemographic and computed tomography scan findings associated with thyroid gland invasion among patients with Laryngeal Squamous Cell Carcinoma

Objective@#We aim to determine the association between preoperative CT scan findings of thyroid cartilage invasion, cricoid cartilage invasion, and paraglottic space involvement with tumor extension to the thyroid gland on final histopathology among patients with laryngeal squamous cell carcinoma (SCC) in a tertiary hospital in the Philippines. @*Methods@#Patients with histopathologically-confirmed laryngeal SCC who underwent total laryngectomy with thyroidectomy while admitted at the public ward of the Department of Otorhinolaryngology, Philippine General Hospital, from January 2013 to December 2019 were included. CT scans were reviewed by 2 blinded independent radiologists. CT scan data including subsite/s involved, thyroid cartilage/cricoid cartilage erosion, paraglottic space involvement, thyroid gland involvement, and thyroid gland involvement on final histopathology were gathered. Clinicopathologic data such as age, T Stage, early tracheostomy, and time between CT scan and surgery were also collected and analyzed. Fisher’s exact test was computed for both clinicopathologic and CT scan data with a significant value having p<0.05. Cramer’s V and phi coefficient were computed for nondichotomous and dichotomous variables, respectively. Odds ratio was also computed for dichotomous variables with p<0.05 on Fisher’s exact test. @*Results@#Fifty-nine (59) men and 4 women were included, aged 43 to 81 years old. Most patients were classified as T3 (n=18) and T4 (n=41) (total=93.7%), with most having transglottic primary tumors (n=29, 46%), and only 8 (12.7%) patients having subglottic tumor involvement on final histopathology. Thyroid cartilage erosion or invasion were noted in 63.4% (n=40) of patients’ CT scans and 58.7% (n=37) of patients’ final histopathology reports. Cricoid cartilage and paraglottic space involvement were often not reported on final histopathology results. Thyroid gland involvement was only noted in the final histopathology reports of 5 patients (7.9%). Significant association between cricoid cartilage findings (p=0.032, Cramer’s V=0.318) or thyroid gland involvement on CT scan (p=0.018, Phi=0.384; OR 13 95% CI 1.797, 94.035) with thyroid gland involvement on final histopathology was noted. The rest of the variables had no significant association with thyroid gland involvement on final histopathology. @*Conclusion@#Cricoid cartilage involvement (erosion or invasion) and thyroid gland involvement on CT scan are associated with thyroid gland involvement on final histopathology in patients with laryngeal SCC. Patients with these CT scan findings may stand to benefit more from thyroidectomy to ensure good margins of resection.

Subjective cognitive functioning in patients with a meningioma: Its course and association with objective cognitive functioning and psychological symptoms.

OBJECTIVE: Although meningioma patients show deficits in objective cognitive functioning (OCF) measured with neuropsychological tests, subjective cognitive functioning (SCF) has received little attention. We investigate SCF from pre- to postsurgery and its associations with OCF, psychological, sociodemographic, and clinical characteristics. METHODS: SCF was measured using the Cognitive Failures Questionnaire (CFQ) 1 day before (T0) and 3 (T3) and 12 months (T12) after surgery. Patients' scores were compared with normative data and changes over time were assessed. The neuropsychological battery CNS Vital Signs and the Hospital Anxiety and Depression Scale were administered. Correlations of SCF with OCF, psychological, sociodemographic, and clinical characteristics were explored. RESULTS: Patients reported significantly better SCF as compared with controls at T0 (N = 54) and T3 (N = 242), but not at T12 (N = 50). A significant decrease in group level SCF was observed from T0 to T12 (n = 24, P < .001). SCF was associated with anxiety at all time points (rs = -0.543 to -0.352) and with depression at T3 and T12 (r = -0.338 and -0.574), but not with OCF, sociodemographic, or clinical characteristics (rs = -0.202 to 0.288). CONCLUSIONS: Meningioma patients experienced better SCF as compared with controls before and 3 months after surgery, which might be the result of phenomena related to disease and recovery. As the findings suggest that cognitive symptoms might increase later on, future studies should further investigate the course of SCF in meningioma patients. In clinical practice, measurements of SCF should be combined with those of OCF and psychological distress in order to determine whether and which interventions are needed.

Interventions for cognitive problems in adults with brain cancer: A narrative review.

INTRODUCTION: Many patients with brain cancer experience cognitive problems. In this narrative review, we comprehensively evaluated empirical studies on various intervention approaches for cognitive problems in these patients. METHODS: Intervention studies that reported effects on cognitive functioning (either objectively tested or subjectively reported) in adult patients with primary and/or secondary brain tumours were identified through online searches in PubMed (MEDLINE) and Web of Science up to 13 March 2019. RESULTS: Of the 364 identified records, 10 pharmacological (including five randomised placebo-controlled trials), 10 cognitive rehabilitation (including five [pilot] RCTs) and two multiple-group exercise studies matched the inclusion criteria. Seventeen of 22 studies had final sample sizes smaller than 40. Several cognitive rehabilitation studies and some pharmacological approaches (donepezil and memantine) showed (at least partial) benefits for cognitive problems in adults with brain cancer. The effects of other pharmacological and exercise interventions were inconclusive and/or preliminary. CONCLUSION: Overall, drawing firm conclusions is complicated due to various methodological shortcomings, including the absence of a (placebo) control group and small sample sizes. Promising effects have been reported for cognitive rehabilitation and some pharmacological approaches. Suggestions for more thorough research with respect to the various approaches are provided.

Cardiomyocyte cell cycle dynamics and proliferation revealed through cardiac-specific transgenesis of fluorescent ubiquitinated cell cycle indicator (FUCCI).

RATIONALE: Understanding and manipulating the cardiomyocyte cell cycle has been the focus of decades of research, however the ultimate goal of activating mitotic activity in adult mammalian cardiomyocytes remains elusive and controversial. The relentless pursuit of controlling cardiomyocyte mitosis has been complicated and obfuscated by a multitude of indices used as evidence of cardiomyocyte cell cycle activity that lack clear identification of cardiomyocyte "proliferation" versus cell cycle progression, endoreplication, endomitosis, and even DNA damage. Unambiguous appreciation of the complexity of cardiomyocyte replication that avoids oversimplification and misinterpretation is desperately needed. OBJECTIVE: Track cardiomyocyte cell cycle activity and authenticate fidelity of proliferation markers as indicators of de novo cardiomyogenesis in post-mitotic cardiomyocytes. METHODS AND RESULTS: Cardiomyocytes expressing the FUCCI construct driven by the α-myosin heavy chain promoter were readily and uniformly detected through the myocardium of transgenic mice. Cardiomyocyte cell cycle activity peaks at postnatal day 2 and rapidly declines thereafter with almost all cardiomyocytes arrested at the G1/S cell cycle transition. Myocardial infarction injury in adult hearts prompts transient small increases in myocytes progressing through cell cycle without concurrent mitotic activity, indicating lack of cardiomyogenesis. In comparison, cardiomyogenic activity during early postnatal development correlated with coincidence of FUCCI and cKit+ cells that were undetectable in the adult myocardium. CONCLUSIONS: Cardiomyocyte-specific expression of Fluorescence Ubiquitination-based Cell Cycle Indicators (FUCCI) reveals previously unappreciated aspects of cardiomyocyte cell cycle arrest and biological activity in postnatal development and in response to pathologic damage. Compared to many other methods and model systems, the FUCCI transgenic (FUCCI-Tg) mouse represents a valuable tool to unambiguously track cell cycle and proliferation of the entire cardiomyocyte population in the adult murine heart. FUCCI-Tg provides a desperately needed novel approach in the armamentarium of tools to validate cardiomyocyte proliferative activity that will reveal cell cycle progression, discriminate between cycle progression, DNA replication, and proliferation, and provide important insight for enhancing cardiomyocyte proliferation in the context of adult myocardial tissue.

Composite infrared spectrometer (CIRS) on Cassini.

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

Composite infrared spectrometer (CIRS) on Cassini: publisher's note.

This publisher's note renumbers the reference list in Appl. Opt.56, 5274 (2017)APOPAI0003-693510.1364/AO.56.005274.

Observation and coherent control of interface-induced electronic resonances in a field-effect transistor.

Electronic defect states at material interfaces provide highly deleterious sources of noise in solid-state nanostructures, and even a single trapped charge can qualitatively alter the properties of short one-dimensional nanowire field-effect transistors (FET) and quantum bit (qubit) devices. Understanding the dynamics of trapped charge is thus essential for future nanotechnologies, but their direct detection and manipulation is rather challenging. Here, a transistor-based set-up is used to create and probe individual electronic defect states that can be coherently driven with microwave (MW) pulses. Strikingly, we resolve a large number of very high quality (Q ∼ 1 × 105) resonances in the transistor current as a function of MW frequency and demonstrate both long decoherence times (∼1 µs-40 µs) and coherent control of the defect-induced dynamics. Efficiently characterizing over 800 individually addressable resonances across two separate defect-hosting materials, we propose that their properties are consistent with weakly driven two-level systems.

Simulated Colonoscopy Objective Performance Evaluation (SCOPE): a non-computer-based tool for assessment of endoscopic skills.

BACKGROUND: The Simulated Colonoscopy Objective Performance Evaluation (SCOPE) was developed to fill the need for a lower-cost, non-virtual-reality (VR)-based assessment tool. This study aimed to evaluate the ability of SCOPE to assess endoscopic skills objectively. METHODS: Four tasks were created using the Kyoto Kagaku colonoscopy model (Kyoto Kagaku Co., Ltd., Kyoto, Japan). The SCOPE tasks included Scope Manipulation (SM) requiring torque and tip deflection to align a shape in the colon with a matching shape on the monitor; Tool Targeting (TT) requiring coordination with biopsy forceps to contact a metal target; Loop Management (LM) requiring prevention, recognition, and reduction of a redundant sigmoid colon with navigation to the cecum; and Mucosal Inspection (MI) requiring identification of simulated polyps during withdrawal and retroflexion. Key performance metrics were identified, and a normalized scoring system was developed. For the study, 35 subjects were stratified into three cohorts based on colonoscopy experience: novice (0-50 colonoscopies; n = 11), intermediate (51-139 colonoscopies; n = 13), and experienced (>140 colonoscopies; n = 11). The subjects performed two trials of all four tasks. RESULTS: Across all four tasks, the experienced endoscopists (E) consistently outperformed the intermediates (I), who in turn outperformed the novices (N). The mean normalized scores with 95 % confidence intervals (CI) are as follows: SM: N (54; range, 26-82), I (92; range, 79-106), E (106; range, 93-118) (p = 0.0006). TT: N (40; range, 24-55), I (77; range, 63-91), E (88; range, 72-105) (p < 0.0001). LM: N (51; range, 24-79), I (80; range, 59-101), E (101; range, 98-105) (p = 0.003). MI: N (73; range, 53-92), I (85; range, 76-95), E (100; range, 91-108) (p = 0.013). Total score: N (218; range, 155-280), I (335; range, 299-371), E (395; range, 371-419) (p < 0.0001). The test-retest reliability (0.6) for the expert total score was respectable. CONCLUSIONS: The validity evidence from this study shows that scores on SCOPE tasks can differentiate between groups expected to have different levels of technical skill. This model shows promise as a low-technology tool for objective assessment or training of endoscopic skills.

Evaluation of online consumer medication information.

BACKGROUND: Millions of Americans search the Internet for health-related information; however, the readability and comprehensiveness of consumer medication information (CMI) on the Internet has not been widely studied. OBJECTIVE: The purpose of this study was to evaluate the readability and comprehensiveness of online CMI. METHODS: The readability and comprehensiveness of consumer drug information found on 3 well-known Web sites (Medline Plus, Yahoo Health, and WebMD) was evaluated; in particular, information related to 10 commonly prescribed medications. Readability was assessed using the Simple Measure of Gobbledygook (SMOG) and Fry Readability Graph (FRG) tools; comprehensiveness of information was evaluated using the Keystone action plan criteria. RESULTS: Using SMOG, the mean reading level of each Web site was 13th grade level or higher. Using the FRG, the mean reading level was 10th grade or higher. Out of the 24 points in the Keystone action plan criteria, information found on each of the Web sites was deemed accurate with mean score of 21, 21, and 19 for Medline Plus, Yahoo Health, and WebMD, respectively. CONCLUSIONS: For the medications reviewed, CMI found on Web sites was accurate when assessed using the Keystone action plan criteria. The readability levels were higher than the recommended sixth grade level.

Laparoscopic repair of a large interstitially incarcerated inguinal hernia.

A 68 year old female presented for elective repair of an abdominal wall hernia. Preoperative CT imaging revealed a right inguinal hernia defect with hernia contents coursing cephalad between the external and internal abdominal oblique muscles. This was consistent with an interstitial inguinal hernia, a rare entity outside of post- traumatic hernias. At operation the hernia contents were reduced laparoscopically. The hernia was then repaired by transitioning to the totally extraperitoneal (TEP) approach using a 15cm X 15cm piece of polyester mesh. The patient had an uneventful recovery. Interstitial hernias are rare, difficult to diagnose and potentially dangerous if left untreated. There is no consensus on the ideal repair of these unique hernias. This represents a minimally invasive repair of an unusual hernia, with a novel approach to diagnose and manage the hernia and its redundant sac.

Rives-Stoppa incisional hernia repair combined with laparoscopic separation of abdominal wall components: a novel approach to complex abdominal wall closure.

BACKGROUND: The Rives-Stoppa incisional hernia repair is the gold standard for mesh repair of complex incisional hernias. The risk of infection can be reduced if fascia is closed over the prosthetic mesh. Fascial closure in large defects may require extensive dissection and can result in devascularization of the overlying skin and denervation of the abdominal wall musculature. Laparoscopic components separation minimizes these risks while facilitating anterior fascial closure. The combined technique of Rives-Stoppa repair augmented by laparoscopic separation of abdominal wall components has not previously been reported. METHODS: We retrospectively reviewed our initial experience with this combined technique for incisional hernia repair. A Rives-Stoppa incisional hernia repair is performed with mesh placed in the retromuscular position. If the anterior fascia cannot be closed, a laparoscopic separation of abdominal wall components is performed to facilitate fascial closure without creation of skin flaps. RESULTS: Six patients were identified. Three patients developed hernias following laparotomy from severe injuries sustained during combat. The other patients included hernia after esophagectomy, retroperitoneal liposarcoma resection, and complicated diverticulitis. Average defect size was 270 cm(2). Complete primary fascial closure anterior to the mesh was achieved in 66% of the patients. No mortalities occurred and at short term follow-up no incisional hernia recurrences have developed. Early post operative complications included a superficial skin infection not involving mesh and a recurrent enterocutaneous fistula. CONCLUSIONS: The authors conclude that Rives-Stoppa repair augmented by laparoscopic components separation is an innovative method for reconstruction of complex abdominal wall defects. Laparoscopic components separation allows fascial closure to be achieved anterior to the mesh in large incisional hernias, which may reduce wound infection rates.

Venous thromboembolism--prophylactic and therapeutic practice guideline.

BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed, which unfortunately results in unacceptable morbidity and mortality in a substantial number of patients. METHOD: The Southern African Society of Thrombosis and Haemostasis reviewed the available literature as well as guidelines from other societies. Specialties represented on the committees included anaesthetics, cardiology, clinical haematology, critical care, gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery, pulmonology and vascular surgery. A draft document was produced, which was revised by consensus agreement. To avoid local bias, the guidelines were adjudicated by recognised independent international external experts. RESULTS AND CONCLUSION. A concise, practical guideline for thrombo-prophylaxis and treatment in medical and surgical patients has been produced for South African conditions. These guidelines will hopefully lead to improved anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder.

Two recent reports have highlighted ANK3 as a susceptibility gene for bipolar disorder (BD). We first reported association between BD and the ANK3 marker rs9804190 in a genome-wide association study (GWAS) of two independent samples (Baum et al., 2008). Subsequently, a meta-analysis of GWAS data based on samples from the US and the UK reported association with a different ANK3 marker, rs10994336 (Ferreira et al., 2008). The markers lie about 340 kb apart in the gene. Here, we test both markers in additional samples and characterize the contribution of each marker to BD risk. Our previously reported findings at rs9804190, which had been based on DNA pooling, were confirmed by individual genotyping in the National Institute of Mental Health (NIMH) waves 1-4 (P=0.05; odds ratio (OR)=1.24) and German (P=0.0006; OR=1.34) samples. This association was replicated in an independent US sample known as NIMH wave 5 (466 cases, 212 controls; P=0.017; OR=1.38). A random-effects meta-analysis of all three samples was significant (P=3 x 10(-6); OR=1.32), with no heterogeneity. Individual genotyping of rs10994336 revealed a significant association in the German sample (P=0.0001; OR=1.70), and similar ORs in the NIMH 1-4 and NIMH 5 samples that were not significant at the P<0.05 level. Meta-analysis of all three samples supported an association with rs10994336 (P=1.7 x 10(-5); OR=1.54), again with no heterogeneity. There was little linkage disequilibrium between the two markers. Further analysis suggested that each marker contributed independently to BD, with no significant marker x marker interaction. Our findings strongly support ANK3 as a BD susceptibility gene and suggest true allelic heterogeneity.