Copy number variations in three children with sudden infant death

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 × 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an ∼3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death.     

Changes in General Nurses' Knowledge of Alcohol and Substance Use and Misuse After Education

PURPOSE.  This study aims to assess the impact of an education program on Australian general nurses' knowledge and competence in identifying and managing patients with alcohol and substance use and misuse, and compare findings with existing literature on mental health nurses.
DESIGN AND METHODS.  Pre- and posttest design without a control group.
FINDINGS.  The nurses' knowledge of safe drinking limits and alcohol withdrawal management improved following the education. Nevertheless, overall the nurses reported a lack of adequate knowledge and competence. Compared to mental health nurses, the nurses in this study had lower levels of knowledge and competence.
PRACTICE IMPLICATIONS.  We suggest several opportunities for general nurses to strengthen their knowledge and skills and the need for a comprehensive and regular education program.     

Weaning critically ill adults from invasive mechanical ventilation: a national survey

Purpose

To determine the stated practices of clinicians in weaning critically ill adults from invasive ventilation.

Methods

We conducted a cross-sectional, self-administered postal survey of Critical Care physicians and respiratory therapists (RTs) in leadership roles at Canadian teaching hospitals. We identified respondents using electronic mail and telephone correspondence. We used rigorous survey methodology to develop, test, and administer the questionnaire.

Results

One hundred ten of 162 (67.9%) clinicians returned the survey with 99 respondents (55 physicians and 44 RTs) completing it either in-part or in-full. Approximately 95% of respondents acknowledged ever performing spontaneous breathing trials (SBTs) in clinical practice. Of these, 95.6% and 32% of respondents reported conducting daily and twice-daily screening to identify SBT candidates, at least sometimes. The three most common techniques to conduct SBTs included; pressure support (PS) with positive end-expiratory pressure (70.8%), continuous positive airway pressure (35.7%), and use of a T-piece (25.0%). PS ventilation was the weaning strategy used most frequently before SBTs. Most respondents (57.1%) considered continuous infusion of sedative-hypnotics to be a relative contraindication to tracheal extubation. However, concurrent administration of low dose vasopressors, inotropes, and analgesic boluses, or continuous analgesic infusions were considered acceptable amongst 60.8%, 73.2%, 78.4% and 58.8% of respondents, respectively. We did not observe regional variation in whether clinicians ever perform SBTs, the ventilatory modes used prior to an SBT nor in the use of PS and SBTs during the weaning process.

Conclusions

Pressure support and SBTs are common features of weaning in Canadian teaching hospitals. Compared to the published literature, our survey suggests that weaning practices have evolved over time and that practice variation may be greater on an international level compared to a national level.     

Preparation of the Dräger Fabius GS™ workstation for malignant hyperthermia-susceptible patients

Purpose

In order to establish guidelines for the preparation of the Dräger Fabius GS? premium anesthetic workstation for malignant hyperthermia-susceptible patients, the authors evaluated the effect of the workstation’s exchangeable and autoclavable components on the washout of isoflurane.

Methods

A Dräger Fabius GS? workstation was primed with 1.5% isoflurane, and exchangeable components were replaced as follows: Group 1: no replacement (control); Group 2: autoclaved ventilator diaphragm and ventilator hose; Group 3: flushed ventilator diaphragm and ventilator hose; Group 4: autoclaved compact breathing system. The fresh gas flow (FGF) was set at 10 L · min^?1, and the concentration of isoflurane in the inspiratory limb of the circle breathing circuit was recorded every minute until an endpoint of 5.0 parts per million (ppm) was achieved, at which time the FGF was reduced to 3 L · min^?1. Six experiments were conducted in each of the four groups.

Results

The time to achieve an isoflurane concentration of 5.0 ppm decreased in the following order: Group 1 (151 ± 17 min) > Group 3 (137 ± 7 min) > Group 4 (122 ± 11 min) > Group 2 (42 ± 6 min) (P < 0.01 vs control). Isoflurane concentration increased approximately fivefold when the FGF was reduced to 3 L · min^?1.

Conclusion

Anesthetic washout from the Dräger Fabius GS? is relatively slow. Although washout was accelerated when the Dräger Fabius GS? was equipped with autoclaved components, the reduction in washout time may be less than that required for this technique to be accepted into clinical practice. A dedicated vapor-free workstation may be preferable for rapid turnover between cases.     

A four phase development model for integrated care services in the Netherlands

Background  

Multidisciplinary and interorganizational arrangements for the delivery of coherent integrated care are being developed in a large number of countries. Although there are many integrated care programs worldwide, the process of developing these programs and interorganizational collaboration is described in the literature only to a limited extent. The purpose of this study is to explore how local integrated care services are developed in the Netherlands, and to conceptualize and operationalize a development model of integrated care.     

Individual, interpersonal, and structural correlates of effective HAART use among urban active injection drug users

Among individuals receiving highly active antiretroviral therapy (HAART), injection drug users (IDUs) are less likely to achieve HIV suppression. The present study examined individual-level, interpersonal, and structural factors associated with achieving undetectable plasma viral load (UVL) among US IDUs receiving recommended HAART. Data were from baseline assessments of the INSPIRE (Interventions for Seropositive Injectors-Research and Evaluation) study, a 4-site, secondary HIV prevention intervention for heterosexually active IDUs. Of 1113 study participants at baseline, 42% (n = 466) were currently taking recommended HAART (34% were female, 69% non-Hispanic black, 26% recently homeless; median age was 43 years), of whom 132 (28%) had a UVL. Logistic regression revealed that among those on recommended HAART, adjusted odds of UVL were at least 3 times higher among those with high social support, stable housing, and CD4 > 200; UVL was approximately 60% higher among those reporting better patient-provider communication. Outpatient drug treatment and non-Hispanic black race and an interaction between current drug use and social support were marginally negatively significant. Among those with high perceived support, noncurrent drug users compared with current drug users had a greater likelihood of UVL; current drug use was not associated with UVL among those with low support. Depressive symptoms (Brief Symptom Inventory) were not significant. Results suggest the major role of social support in facilitating effective HAART use in this population and suggest that active drug use may interfere with HAART use by adversely affecting social support. Interventions promoting social support functioning, patient-provider communication, stable housing, and drug abuse treatment may facilitate effective HAART use in this vulnerable population.     

Somatic augmentation strategies in clozapine resistance--what facts?

BACKGROUND: Polypharmacy without evidence-based support is sometimes needed for patients treated with 40% to 70% clozapine who are clozapine nonresponders. Several somatic augmentation strategies are proposed in the scientific literature, with different levels of evidence for safety and efficacy. OBJECTIVES: The purpose of the present study is to review the available literature on the efficacy and safety of clozapine augmentation with somatic agents other than antipsychotics. The following classes of agents are considered: (1) mood stabilizers, (2) antidepressants, (3) electroconvulsive therapy and repetitive transcranial magnetic stimulation, (4) glutamatergic agents, (5)fatty acids supplements, and (6) benzodiazepines. RESULTS: Case controls and small-size clinical trials largely dominate the literature, limiting the power to draw conclusions concerning safety issues and the meaning of negative studies. Moreover, variable definitions of clozapine resistance, heterogeneous outcome measures, and short duration of treatment trials are additional limitations. CONCLUSION: Generally, adjunctive strategies for clozapine-resistant patients remain based on scarce evidence of efficacy and significant safety concerns. Low-frequency repetitive transcranial magnetic stimulation, fatty acids supplements, and mirtazapine showed good tolerability and some efficacy, but the results need replication.     

Effects of desipramine on irritable bowel syndrome compared with atropine and placebo

Antidepressant treatment trials of irritable bowel syndrome (IBS) have suggested beneficial effects. Twenty-eight patients with the disorder (9 constipation-predominant, 19 diarrhea-predominant_ completed a double-blind crossover study using desipramine, atropine, and placebo in random sequence. A four-week observation period preceded three six-week test periods. Bowel habits, abdominal distress, and affect were reported daily and in biweekly evaluations. Psychological assessments and rectosigmoid contractile studies were done in each period. Stool frequency, diarrhea, abdominal pain, depression, and slow contractions decreased significantly more in diarrhea-predominant patients during desipramine compared with placebo and atropine treatments. Diarrheaprone patients' depression scores fell more in all periods than constipation-prone patients. Fifteen patients (13 diarrhea-predominant) improved globally during desipramine, five during placebo and six during atropine treatments. Desipramine may be helpful in treating IBS, perhaps through antidepressant and antimuscarinic effects.Supported in part by a grant from the National Institute of Mental Health (MH-34115).