Deferred consent in a minimal-risk study involving critically ill subarachnoid hemorrhage patients

INTRODUCTION:

Alterations from first-party and surrogate decision-maker consent can enhance the feasibility of research involving critically ill patients.

OBJECTIVE:

To describe the use of a deferred-consent model to enable participation of critically ill patients in a minimal-risk biomarker study.

METHODS:

A prospective observational study was conducted in which serum biomarker samples were collected three times daily over the first 14 days following aneurysmal subarachnoid hemorrhage. Sample collection was initiated on intensive care unit admission and consent was obtained when research personnel could approach the patient or the patient’s surrogate decision maker.

RESULTS:

Twenty-seven patients were eligible for the study, of whom only five were capable of providing informed consent. Full consent was obtained for 21 (78%) patients through self- (n=4) and surrogate (n=17) consent. Partial consent or refusal (only permitting the collection of blood samples as a part of routine care or use of data) occurred in three patients. Among the 22 consents sought from surrogates, three (11%) refused participation. The refusals included the sickest patients in the cohort. Once consent was provided, no patient or surrogate withdrew consent before study completion.

DISCUSSION:

Use of a deferred consent model enabled participation of critically ill patients in a minimal-risk biomarker study with no withdrawals.

CONCLUSIONS:

Further research and enhanced awareness of the potential utility of hybrid models, including deferred consent in addition to patient or surrogate consent, in the conduct of low-risk and minimally interventional time-sensitive studies of critically ill patients are required.     

Behavioral parent training to address sleep disturbances in young children with autism spectrum disorder: a pilot trial

Objectives

A large percentage of children with autism spectrum disorders (ASD) have bedtime and sleep disturbances. However, the treatment of these disturbances has been understudied. The purpose of our study was to develop a manualized behavioral parent training (BPT) program for parents of young children with ASD and sleep disturbances and to test the feasibility, fidelity, and initial efficacy of the treatment in a small randomized controlled trial (RCT).

Participants and methods

Parents of a sample of 40 young children diagnosed with ASD with an average age of 3.5 years were enrolled in our study. Participants were randomized to either the BPT program group or a comparison group who were given nonsleep-related parent education. Each participant was individually administered a 5-session program delivered over the 8-week study. Outcome measures of feasibility, fidelity, and efficacy were collected at weeks 4 and 8 after the baseline time point. Children’s sleep was assessed by parent report and objectively by actigraphy.

Results

Of the 20 participants in each group, data were available for 15 participants randomized to BPT and 18 participants randomized to the comparison condition. Results supported the feasibility of the manualized parent training program and the comparison program. Treatment fidelity was high for both groups. The BPT program group significantly improved more than the comparison group based on the primary sleep outcome of parent report. There were no objective changes in sleep detected by actigraphy.

Conclusions

Our study is one of few RCTs of a BPT program to specifically target sleep disturbances in a well-characterized sample of young children with ASD and to demonstrate the feasibility of the approach. Initial efficacy favored the BPT program over the comparison group and suggested that this manualized parent training approach is worthy of further examination of the efficacy within a larger RCT.     

Systemic use of non‐biologic corticosteroids in orofacial diseases

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most especially the corticosteroids (corticosteroids). This study reviews the corticosteroids in systemic use in management of orofacial mucocutaneous diseases; subsequent studies discuss corticosteroid‐sparing agents used in the management of orofacial diseases, such as calcineurin inhibitors used to produce immunosuppression; purine synthetase inhibitors; and cytotoxic and other immunomodulatory agents.     

Increased urinary nitric oxide oxidation products in children with active coeliac disease

BACKGROUND: Nitric oxide (NO) production catalyzed by iNOS (inducible NO synthase) is thought to take place mainly in macrophages after activation by inflammatory mediators. NO is subsequently oxidized to nitrite and nitrate, which are excreted in urine. The concentration of inflammatory mediators in small bowel biopsy specimens from patients with coeliac disease is increased. The latter could induce increased NO production by stimulation of intestinal macrophage iNOS, resulting in high levels of urinary NO oxidation products, nitrite and nitrate (NOx). AIM: In the present study we evaluated the urinary NOx/creatinine ratios in children with active coeliac disease (n = 22), coeliac disease patients on a gluten-free diet (n = 9), healthy (n = 11) and sick control children (n = 18). METHODS: The Griess reagent method was used for measuring urinary NOx. RESULTS: Median NOx/creatinine ratios of active coeliac disease patients, coeliac disease patients on a gluten-free diet, healthy and sick control patients were 1.21, 0.19, 0.10 and 0.13 mmol/mmol, respectively. All active coeliac disease patients showed increased NOx/ creatinine ratios. Urinary NOx/creatinine ratios of the active coeliac disease patients were significantly higher than those of healthy controls (p < 0.0001), sick controls (p < 0.0001) and coeliac disease patients on a gluten-free diet (p < 0.0001). CONCLUSION: The urinary NOx/creatinine ratio is increased in patients with active coeliac disease and reverts to normal on a gluten-free diet.     

Actigraphic and parent reports of sleep patterns and sleep disorders in children with subtypes of attention-deficit hyperactivity disorder

STUDY OBJECTIVE: To describe parent-reported and actigraphically assessed sleep patterns and sleep disorders in stimulant-medication-free children with attention-deficit/hyperactivity disorder (ADHD), divided according to ADHD subtype. PARTICIPANTS: Seventy-one stimulant-medication-free children with a clinical diagnosis of ADHD (8 girls; mean 8.8 years (SD 2.6), range 3-15 years) recruited from child psychiatry clinics. MEASUREMENTS: ADHD: ADHD Rating Scale DSM IV- Home Version to subdivide children into those with predominantly attention deficit, mainly hyperactivity, and those with both aspects equally. Sleep: Parent-completed sleep diary, clinical history, and 5 nights of actigraphy. RESULTS: Parents reported a wide range of frequently occurring sleep disturbances in their children. However, the objective sleep patterns were not abnormal and did not differ between the ADHD subtypes, and objective sleep patterns did not predict ADHD severity. There was poor correspondence between parent report and actigraphy. Careful clinical consideration of each case suggested that sleep disorders may be widespread in this group of children; only 8 of the 71 children had no discernable likely sleep disorder. Symptoms of sleep-disordered breathing, sleeplessness and reports of restless legs featured prominently. CONCLUSIONS: Parents of children with ADHD may not be accurate reporters of their children's sleep pattern and/or the sleep disturbances that come to parents' attention are not best detected by actigraphy. Results highlight the prominence of parent-reported sleep disturbance in children with ADHD and the need for clinicians to routinely screen for the presence of sleep disorders and assess detailed sleep physiology where indicated.     

Intergenerational instability of the CAG repeat of the gene for Machado- Joseph disease (MJD1) is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects intergenerational instability of the CAG repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were found to result in significantly greater instability of the CAG repeat compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded (CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic regression analysis revealed that the relative risk for a large intergenerational change in the number of CAG repeat units (< -2 or > 2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal transmission than in that of maternal transmission and 7.4-fold (95% CI: 2.4-23.3) higher in the case of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of transmission from a parent with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase in the relative risk compared with that of maternal transmission and the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The results suggest that an inter- allelic interaction is involved in the intergenerational instability of the expanded CAG repeat.      

Hydrocelectomy under local anaesthesia in a Nigerian adult population

Background

Hydrocele is abnormal collection of serous fluid in the tunica vaginalis or a patent processus vaginalis. It is commonly encountered in our practice and often requires surgical treatment. However in our setting and in many underdeveloped countries, availability of general anaesthetic service is poor due to lack of trained personnel and equipment.

Objectives

To ascertain the practicability and acceptability of hydrocelectomy under sedation and local anaesthesia in Nigerian adults with hydrocele

Patients and Methods

A prospective study was carried out over a two year period on patients that had hydrocelectomy at the surgery unit of the Obafemi Awolowo University Teaching Hospitals Complex, Wesley Guild Hospital, Ilesa. Consecutive patients with diagnosis of hydrocele who consented had hydrocelectomy using intramuscular diazepam sedation and spermatic-cord block with 0.5% plane xylocaine and the scrotum infiltrated with same along the line of incision.

Results

Fifty adult patients were studied: age range 15–94 years. Eighty percent of the patients had unilateral hydrocele and the commonest type was vaginal hydrocele (94%). All patients had hydrocelectomy, 96% were under local anaesthesia while 4% were converted to general anaesthesia. All patients except one prefer to have future surgery under such local anaesthesia and sedation.

Conclusion

Hydrocelectomy under local anaesthesia and sedation is practicable and was tolerated and accepted by the adults patients studied.