Consensus guidelines on analgesia and sedation in dying intensive care unit patients

Background

Intensivists must provide enough analgesia and sedation to ensure dying patients receive good palliative care. However, if it is perceived that too much is given, they risk prosecution for committing euthanasia. The goal of this study is to develop consensus guidelines on analgesia and sedation in dying intensive care unit patients that help distinguish palliative care from euthanasia.

Methods

Using the Delphi technique, panelists rated levels of agreement with statements describing how analgesics and sedatives should be given to dying ICU patients and how palliative care should be distinguished from euthanasia. Participants were drawn from 3 panels: 1) Canadian Academic Adult Intensive Care Fellowship program directors and Intensive Care division chiefs (N = 9); 2) Deputy chief provincial coroners (N = 5); 3) Validation panel of Intensivists attending the Canadian Critical Care Trials Group meeting (N = 12).

Results

After three Delphi rounds, consensus was achieved on 16 statements encompassing the role of palliative care in the intensive care unit, the management of pain and suffering, current areas of controversy, and ways of improving palliative care in the ICU.

Conclusion

Consensus guidelines were developed to guide the administration of analgesics and sedatives to dying ICU patients and to help distinguish palliative care from euthanasia.     

Body weight and abdominal fat gene expression profile in response to a novel hydroxycitric acid-based dietary supplement

Obesity is a global public health problem, with about 315 million people worldwide estimated to fall into the WHO-defined obesity categories. Traditional herbal medicines may have some potential in managing obesity. Botanical dietary supplements often contain complex mixtures of phytochemicals that have additive or synergistic interactions. The dried fruit rind of Garcinia cambogia, also known as Malabar tamarind, is a unique source of (-)-hydroxycitric acid (HCA), which exhibits a distinct sour taste and has been safely used for centuries in Southeastern Asia to make meals more filling. Recently it has been demonstrated that HCA-SX or Super Citrimax, a novel derivative of HCA, is safe when taken orally and that HCA-SX is bioavailable in the human plasma as studied by GC-MS. Although HCA-SX has been observed to be conditionally effective in weight management in experimental animals as well as in humans, its mechanism of action remains to be understood. We sought to determine the effects of low-dose oral HCA-SX on the body weight and abdominal fat gene expression profile of Sprague-Dawley rats. We observed that at doses relevant for human consumption dietary HCA-SX significantly contained body weight growth. This response was associated with lowered abdominal fat leptin expression while plasma leptin levels remained unaffected. Repeated high-density microarray analysis of 9960 genes and ESTs present in the fat tissue identified a small set (approximately 1% of all genes screened) of specific genes sensitive to dietary HCA-SX. Other genes, including vital genes transcribing for mitochondrial/nuclear proteins and which are necessary for fundamental support of the tissue, were not affected by HCA-SX. Under the current experimental conditions, HCA-SX proved to be effective in restricting body weight gain in adult rats. Functional characterization of HCA-SX-sensitive genes revealed that upregulation of genes encoding serotonin receptors represent a distinct effect of dietary HCA-SX supplementation.     

A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome)

Rump P, Niessen RC, Verbruggen KT, Brouwer OF, de Raad M, Hordijk R. A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome). Opitz–Kaveggia syndrome is a rare X‐linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty‐three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz–Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.     

Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome

Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation.     

The influence of naturally occurring heterophilic anti-immunoglobulin antibodies on direct measurement of serum proteins using sandwich ELISAs

Sandwich ELISAs have become a widely used method for the quantitative detection of serum proteins. However, they can be biased by a variety of interfering substances. As reported recently, we observed false-positive levels of interferon (IFN)-alpha and -beta in up to 27% of sera from healthy blood donors using commercial ELISAs. We now demonstrate that two different groups of naturally occurring heterophilic antibodies (IgG-type) are responsible for these titers. Group I (representing 85% of positive samples) binds to the Fab region of IgG from goat, mouse, rat, horse, and bovidae (but not rabbit). Group II (15%) recognizes an epitope in the Fc region of mouse, horse, bovine, and rabbit (but not goat or rat) immunoglobulins. The antibodies did not crossreact with human IgG subclasses but contributed to false-positive IgG rheumatoid factor levels obtained using a commercially available ELISA. To investigate the susceptibility of assays to these artifacts, various combinations of capture and detection antibodies have been tested. On this basis, we defined the relative risks that standard ELISAs might be influenced by heterophilic anti-immunoglobulin antibodies. In general, assays that use monoclonal antibodies for both capture and detection are less susceptible than others which include at least one polyclonal antiserum. However, only systems utilizing rabbit F(ab')(2) fragments have been found to be immune to this interference.     

Long-term followup and outcome of continent catheterizable vesicocstomy using the Rink modification

PURPOSE: Multiple techniques have been described to create a Mitrofanoff channel in the pediatric population. A small subset of patients only requires creation of a catheterizable channel without bladder augmentation. These patients are ideal candidates for a procedure that avoids the use of intestine, especially in the absence of a suitable appendix. We used a modification of the Casale vesicostomy, as described by Rink, to create a continent vesicostomy in these children. We report our long-term experience with this technique. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients who underwent continent vesicostomy at our institution between 1992 and 2000. Patient diagnosis, stomal site, associated bladder procedures, stomal continence, followup and complications associated with continent vesicostomy were documented. RESULTS: Of the 31 patients who underwent continent vesicostomy, as described by Rink, 14 were female and 17 were male. Average age was 9 years (range 2.5 to 22). Primary diagnosis included neuropathic bladder in 15 cases, the prune-belly syndrome in 6, cloacal exstrophy/anomaly in 5 and other in 5. The stoma was placed in the lower abdomen in 17 patients, in the umbilicus in 7 and in a neoumbilicus in 7. Simultaneous procedures included ureteral reimplantation in 8 cases, bladder augmentation in 5, bladder neck surgery in 4 and reduction cystoplasty in 2. Mean followup was 41 months. All patients achieved excellent stomal continence. Complications included stomal stenosis requiring revision in 14 cases (45%). Stenosis developed in 60% of the patients with neuropathic bladder and in 86% with an umbilical stoma. Eventually 6 patients underwent conversion to an alternative catheterizable channel. CONCLUSIONS: Continent vesicostomy can be performed successfully when there is any underlying bladder pathology with 100% stomal continence. Despite the higher rate of stomal problems with this type of Mitrofanoff channel we think that continent vesicostomy is a reasonable alternative in patients with a large bladder requiring only catheterizable channel creation. Because of the excellent results reported with the Monti-Yang technique, we would currently recommend this procedure over continent vesicostomy when bowel is used for bladder reconstruction.     

Mammography uptake predictors in older women

BACKGROUND: In women aged under 65 years, socio-economic factors and general health behaviours are important predictors of mammography uptake. Little is known about whether these factors are important in older women. OBJECTIVE: To examine a broad range of mammography uptake predictors in women aged 65 and older registered with a London (UK) practice. METHODS: A survey of all female patients aged 65 and over (n = 613) in a south London practice included questions on mammography and cervical screening, general health and functional ability, socio-economic factors, mental health, health behaviours, and attitudes to health. Associations between mammography uptake and other factors were examined using logistic regression. RESULTS: The response rate was 70% (432/613). Increased age was strongly associated with decreased mammography uptake. Additionally, socio-economic factors and general health behaviours (previous cervical smear, drinking alcohol and being a non-smoker) were independently predictive of mammography uptake. Measures of physical and mental health and health attitudes were not independent predictors. Restricting analyses to the oldest women, outside the national screening programme, gave very similar results. CONCLUSIONS: In this sample of older women, socio-economic factors and general health behaviours were more predictive of mammography uptake than measures of physical and mental health or attitudes to health. Knowledge of these predictors is of increasing importance as the screening programme in the UK is extended up to age 70.