Validation of a Portuguese version of a generic health quality-of-life questionnaire for children with neurological and neuropsychiatric disorders, including epilepsy

PURPOSE: To validate a Portuguese version of a generic HRQL instrument already used for children with epilepsy. To analyze differences of scores among children with epilepsy and co-morbidities in contrast to other neurological and neuropsychiatric diagnosis, especially Attention Deficit and Hyperactivity Disorder (ADHD). METHODS: A total of 194 children (64 with epilepsy, 94 with ADHD and 38 with other neurological or neuropsychiatric diagnosis) were consecutively seen in a neuropaediatric ambulatory unit. Parents or caregivers responded to a Portuguese version of ICIS (Impact of Childhood Illness Scale). The questionnaire was analyzed for internal consistency and face validity. Clinical and socio-demographic variables were also analyzed. RESULTS: Internal consistency, analyzed by Cronbach's alpha showed good results for total and combined scores and all sections of ICIS, except for the section "impact of illness and its treatment". The diagnostic categories differed in several ICIS sections, with the worst scores for children with epilepsy and co-morbidities. Children who only had epilepsy had a worse score on the section about treatment impact compared with children with ADHD, but better scores in relation to disease impact in development and parents/family. In the epilepsy group, HRQL scores were worst for symptomatic epilepsy, whilst seizure control and socioeconomic factors affected each section of the instrument in different ways. CONCLUSIONS: ICIS Portuguese version has good psychometric properties. It is a useful tool for analyzing HRQL in children with epilepsy and other neurodevelopmental and psychiatric disorders. Epilepsy and psychiatric co-morbidity seems to have an additive impact on a child's HRQL. This result is clinically important since epilepsy management must include not only seizure control but also mental health support.     

Systematic review and meta-analyses of randomized controlled trials examining tinnitus management

Objectives/Hypothesis:

To evaluate the existing level of evidence for tinnitus management strategies identified in the UK Department of Health's Good Practice Guideline.

Study Design:

Systematic review of peer‐reviewed literature and meta‐analyses.

Methods:

Searches were conducted in PubMed, Cambridge Scientific Abstracts, Web of Science, and EMBASE (earliest to August 2010), supplemented by hand searches in October 2010. Only randomized controlled trials that used validated questionnaire measures of symptoms (i.e., measures of tinnitus distress, anxiety, depression) were included.

Results:

Twenty‐eight randomized controlled trials met our inclusion criteria, most of which provide moderate levels of evidence for the effects they reported. Levels of evidence were generally limited by the lack of blinding, lack of power calculations, and incomplete data reporting in these studies. Only studies examining cognitive behavioral therapy were numerous and similar enough to perform meta‐analysis, from which the efficacy of cognitive behavioral therapy (moderate effect size) appears to be reasonably established. Antidepressants were the only drug class to show any evidence of potential benefit.

Conclusions:

The efficacy of most interventions for tinnitus benefit remains to be demonstrated conclusively. In particular, high‐level assessment of the benefit derived from those interventions most commonly used in practice, namely hearing aids, maskers, and tinnitus retraining therapy needs to be performed.     

Molecular confirmation of the unique phenotype of epidermolysis bullosa simplex with mottled pigmentation

BACKGROUND: A distinctive subtype of epidermolysis bullosa simplex, with the additional feature of mottled pigmentation (EBS-MP), was initially characterized in a Swedish family in 1979, and seven further families have been reported. Features of EBS-MP that are observed in most affected patients include acral blistering early in childhood, mottled pigmentation distributed in a number of sites, focal punctate hyperkeratoses of the palms and soles, and dystrophic, thickened nails. The genetic basis of EBS-MP has been ascribed in five unrelated families to a heterozygous point mutation, P25L, in the non-helical V1 domain of K5. OBJECTIVES: We report a clinical, ultrastructural and molecular study of two of the earliest families to be clinically characterized as EBS-MP. METHODS: The P25L mutation was identified in all affected members of each of these families, bringing the total number of EBS-MP families with this mutation to seven. RESULTS: This unusual recurrent mutation may uniquely cause EBS-MP. CONCLUSIONS: While the exact molecular mechanisms by which this mutation causes epidermolysis, palmoplantar keratoderma and pigmentation remain elusive, we suggest possible molecular mechanisms through which the P25L substitution could cause this unusual phenotype.     

Ambient temperature affects thrombotic potential at rest and following exercise

Introduction

During exercise, ischemic risk increases, possibly due to changes in coagulation and fibrinolytic activity. Previous research suggests ambient temperature affects resting thrombotic potential, but the effect of heat and cold on hemostasis during exercise is unknown. The purpose of this study was to assess changes in coagulation and fibrinolysis during maximal exercise in hot and cold temperatures, and to compare those responses to exercise under temperate conditions.

Materials & Methods

Fifteen healthy men completed maximal exercise tests in hot (30 °C), temperate (20 °C) and cold (5° - 8 °C) temperatures. Blood samples were obtained before and immediately after exercise and analyzed for concentrations of thrombin-antithrombin III (TAT), active tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Results were analyzed by ANOVA.

Results

A main effect of time was observed for TAT (temperate = 1.71 ± 0.82 - 2.61 ± 0.43 ng/ml, hot = 1.81 ± 0.73 - 2.62 ± 0.67 ng/ml, cold = 2.33 ± 0.65 - 2.89 ± 0.81 ng/ml, PRE to POST, respectively) and tPA activity (temperate = 0.72 ± 0.44 - 2.71 ± 0.55 IU/ml, hot = 0.72 ± 0.38 - 2.64 ± 0.61 IU/ml, cold = 0.86 ± 0.45 - 2.65 ± 0.77 IU/ml, PRE to POST, respectively). A trend was observed for the PAI-1 response to exercise (temperate = 14.5 ± 23.7 - 12.3 ± 20.2 IU/ml, hot = 15.1 ± 26.5 - 10.0 ± 15.1 IU/ml, cold = 10.5 ± 10.4 - 7.9 ± 9.7 IU/ml, PRE to POST, respectively, p = 0.08). TAT concentrations were significantly higher in cold compared to temperate and hot conditions.

Conclusion

Coagulation potential is elevated during exposure to cold temperatures. These data suggest that risk of an ischemic event may be elevated in the cold.     

Pregnancy after Fontan repair of complex congenital heart disease

We describe four successful pregnancies in three women who had previously had a Fontan repair for congenital heart disease. Each pregnancy resulted in a live birth and there was no maternal mortality The infants were premature, being delivered at 26, 30 and 35 weeks, and weighing 1,020, 1,333 and 1,930 g respectively The fourth infant was born at 32 weeks and no birthweight is available. Maternal complications occurred and were those anticipated after a Fontan repair. Two mothers required treatment for supraventricular arrhythmias (atrial flutter and fibrillation). Ventricular failure was present in two mothers and required ongoing drug treatment. Raised systemic venous pressures caused peripheral oedema in two mothers and hepatomegaly and ascites in one mother. The physiology, potential complications, anaesthetic concerns and drug treatment in pregnancy after Fontan repair are discussed.     

Tnk1/Kos1 knockout mice develop spontaneous tumors

Tnk1/Kos1 is a non-receptor protein tyrosine kinase implicated in negatively regulating cell growth in a mechanism requiring its intrinsic catalytic activity. Tnk1/Kos1 null mice were created by homologous recombination by deleting the catalytic domain. Both Tnk1(+/-) and Tnk1(-/-) mice develop spontaneous tumors, including lymphomas and carcinomas, at high rates [27% (14 of 52) and 43% (12 of 28), respectively]. Tnk1/Kos1 expression is silenced in tumors that develop in Tnk1(+/-) mice but not in adjacent uninvolved tissue, and silencing occurs in association with Tnk1 promoter hypermethylation. Tissues and murine embryonic fibroblasts derived from Tnk1/Kos1-null mice exhibit proportionally higher levels of basal and epidermal growth factor-stimulated Ras activation that results from increased Ras-guanine exchange factor (GEF) activity. Mechanistically, Tnk1/Kos1 can directly tyrosine phosphorylate growth factor receptor binding protein 2 (Grb2), which promotes disruption of the Grb2-Sos1 complex that mediates growth factor-induced Ras activation, providing dynamic regulation of Ras GEF activity with suppression of Ras. Thus, Tnk1/Kos1 is a tumor suppressor that functions to down-regulate Ras activity.     

The evolution of urethral stricture and urethroplasty practice over 15 years: A single-center,single-surgeon, 1319 urethroplasty analysis

IntroductionThe management of urethral stricture has evolved over the last several decades. We sought to analyze urethral stricture and urethroplasty trends at a tertiary referral center over a 15-year period.MethodsPatients undergoing urethroplasty by a single surgeon from August 2003 to July 2018 were analyzed. Patient demographics, urethroplasty techniques, and outcomes were collected in a prospectively maintained database and were categorized into three five-year tertiles based on date of surgery. These tertiles were subsequently retrospectively analyzed for trends and changes in practice.ResultsA total of 1319 urethroplasties were completed over the study period. During the first five years (T1), 299 urethroplasties were performed, with 431 and 589 performed in T2 and T3, respectively. Mean overall patient age was 46.8 years, which increased significantly over time (p<0.001). Idiopathic strictures were most common (n=516, 39.1%) and unchanged over time, while proportionately radiation-induced strictures increased (n=9, 3.0% [T1], n=22, 5.1% [T2], n=51, 8.7% [T3]; p=0.001) as did iatrogenic and lichen sclerosus strictures. Mean stricture length (4.7 cm [T1], 4.8 cm [T2], 4.0 cm [T3]; p<0.001) and the mean number of prior endoscopic procedures (3.4 [T1], 3.9 [T2], and 2.5 [T3]; p<0.001] decreased over time. Single-stage urethroplasty with buccal mucosa was the most common technique performed (n=656, 49.7%) that increased in prevalence (p=0.009), while both flap and staged techniques decreased (p=0.008, p=0.004, respectively). Overall success rate was 90.1% (n=1106), which improved significantly with time (n=248, 86.7% [T1], n=359, 90.0% [T2], n=499, 93.4% [T3]; p=0.001).ConclusionsWe observed that patients and treatment of urethral stricture evolved over 15 years in practice, with an increase in patient age, radiation, and iatrogenic and lichen sclerosus strictures, while demonstrating a decrease in stricture length and the number of prior endoscopic procedures performed. Increased use of single-stage urethroplasty using buccal mucosa was observed, which may have contributed to an increase in urethroplasty success over time.

KEY MESSAGES

• Urethroplasty practice has evolved over the last 15 years likely in response to urological society guidelines, innovations in surgical technique, and locoregional referral patterns.
• With time, urethroplasty volume increased, along with changes in patient demographics, stricture etiology, and complexity.
• In the last five years, stricture length decreased, along with a reduction in the number of endoscopic procedures performed prior to referral, with a concurrent increase in urethroplasty success.
• There has been a significant trend toward wide-spread adoption of single-stage urethroplasty with buccal mucosa at the expense of staged and penile fasciocutaneous flap reconstruction.

     

What proportions of focal liver lesions detected by unenhanced ultrasound are inconclusive?

In August 2012, the National Institute for Health and Care Excellence produced positive diagnostics guidance on the ultrasound contrast agent SonoVue®, but recommended further research involving an estimation of the proportion of unenhanced ultrasound scans reporting, but not characterising, focal liver lesions, particularly in cirrhotic livers. Patient records from the Radiology Information System of an acute hospital trust were progressively filtered based on categorical fields and keywords in the free text reports, to obtain ultrasound records including the liver that were appropriate for manual analysis. In total, 21,731 records referred from general practice or out-patient clinics were analysed. Patients described as having cirrhosis were analysed as a subgroup. After automatic exclusion of records considered likely to be negative, 5812 records were manually read and categorised as focal liver lesion inconclusive, benign or malignant. In the general practice cohort of 9175 records, 746 reported the presence of one or more focal liver lesions, with 18.4% (95% CI 15.7% to 21.3%) of these records mentioning an inconclusive focal liver lesion. In the out-patient cohort of 12,556 records, 1437 reported one or more focal liver lesions, and 29.4% (95% CI 26.9% to 32.0%) of these were inconclusive. Cirrhosis was reported in 10.8% of the out-patient scans that also reported a focal liver lesion, and 47.4% (95% CI 39.3% to 55.6%) of these scans had an inconclusive focal liver lesion, compared with 27.3% (95% CI 24.9% to 29.8%) that were inconclusive in non-cirrhotic livers (odds ratio 2.4; 95% CI 1.7 to 3.4). This retrospective study indicates that unenhanced ultrasound scans, in which a focal liver lesion is detected, are frequently inconclusive, with the probability of an inconclusive scan being greater in out-patient than general practice referrals. Inconclusive focal liver lesions were also reported in greater proportions of cirrhotic than non-cirrhotic livers. The results of this research will inform future updates of National Institute for Health and Care Excellence diagnostics guidance.