Improving the safety of neuromuscular blocking agents: a statement from the USP Safe Medication Use Expert Committee.

PURPOSE: Recommendations of the interdisciplinary Safe Medication Use Expert Committee of the United States Pharmacopeia (USP) to assist health care professionals, manufacturers, and organizations in handling neuromuscular blocking agents (NMBAs) safely and effectively are discussed. SUMMARY: Review and analysis of the USP Medication Errors Reporting Program and MEDMARX program databases showed a continuing risk of patient harm or death due to errors with NMBAs. Medication errors involving wrong concentrations, wrong doses, wrong drugs, look-alike packaging, and sound-alike names, combined with lack of monitoring and communication, have been associated with the use of NMBAs in health care institutions. Serious adverse events occur when NMBAs are used without adequate safeguards. Recommendations for improving safety were developed through review and discussion of root causes and areas of concern with these medications. CONCLUSION: Medical errors with NMBAs continue to result in patient morbidity and mortality. Increased awareness and action on the part of all parties involved are needed to improve the safety of this class of medications.     

Serum 25-hydroxyvitamin D concentrations of New Zealanders aged 15 years and older

Introduction Vitamin D plays an important role in bone health. Our purpose was to measure serum 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=2,946) of New Zealanders aged 15 years and over.Findings Mean (99% CI) serum 25-hydroxyvitamin D concentrations were 47 (45–50) nmol/l in women and 52 (49–55) nmol/l in men. Mean concentrations in New Zealand European and Others (NZEO, n=2,440), Mori (n=370), and Pacific (n=136) were 51 (49–53), 42 (38–46) and 37 (33–42) nmol/l, respectively. Three percent of New Zealanders had serum 25-hydroxyvitamin D concentrations indicative of deficiency (≤17.5 nmol/l); 48% and 84% were insufficient based on cutoffs of ≤50 and ≤80 nmol/l. Determinants of serum 25-hydroxyvitamin D concentrations in women were age, ethnicity, obesity, latitude and season; determinants in men were ethnicity and season. Serum 25-hydroxyvitamin D in women declined with age; mean concentration was 13 (8–18) nmol/l lower in women 65 years or older and 9 (5–13) nmol/l lower in women 45–64 years compared with women 15–18 years. Spring to summer differences in serum 25-hydroxyvitamin D were 31 (28–34) and 28 (25–31) nmol/l in women and men, respectively. Obese women had lower vitamin status than normal-weight women by 6 (3–10). Women living in the South Island had a mean serum 25-hydroxyvitamin D that was 6 (3–9) nmol/l lower than women living in the North Island. Ethnicity and season are the major determinants of serum 25-hydroxyvitamin D in New Zealanders.Conclusion The high prevalence of vitamin D insufficiency in New Zealanders, particularly in older women, may warrant strategies to improve vitamin D status.     

WHO: reaching out to all

This article explains how the concept of health for all developed within the context of the history of the World Health Organization (WHO). By the early 1970s a new idea was taking shape in WHO. Medical services were failing to reach vast numbers. Health would have to emerge from the people themselves. In the heat of discussion the new strategy was clarified and given a name--primary health care (PHC). An ambitious target was set for it--no less than health for all by the year 2000. It was decided that the community itself had to be involved in planning and implementing its own health care. A new type of health worker was called for, chosen by the people from among themselves and responsible to the community but supported by the entire health system. In virtually all countries, the emphasis on curative care would have to be balanced by an equal emphasis on prevention. Almost 90% of WHO's Member States were prepared to share with one another detailed information about the problems facing their health systems. Industrial countries were beginning to realize that sophisticated medical technology was no guarantee of good health and that health for all through PHC offered an alternative. Millions of health workers have been trained, extending services to low-income groups that had no access to modern health care. Among health professionals, lack of understanding of the PHC concept and insufficient concern for social equity remain the principal constraints. Another problem is that expenditure on health care tends to be viewed as a drain on scarce resources rather than as an investment in the nation's future. The mommentum of health for all can be sustained only by governments implementing at home the policies they have collectively agreed on at The World Health Assembly in Geneva.     

The 2.0-Å resolution crystal structure of a trimeric antibody fragment with noncognate VH–VL domain pairs shows a rearrangement of VH CDR3

The 2.0-Å resolution x-ray crystal structure of a novel trimeric antibody fragment, a “triabody,” has been determined. The trimer is made up of polypeptides constructed in a manner identical to that previously described for some “diabodies”: a V_L domain directly fused to the C terminus of a V_H domain—i.e., without any linker sequence. The trimer has three Fv heads with the polypeptides arranged in a cyclic, head-to-tail fashion. For the particular structure reported here, the polypeptide was constructed with a V_H domain from one antibody fused to the V_L domain from an unrelated antibody giving rise to “combinatorial” Fvs upon formation of the trimer. The structure shows that the exchange of the V_L domain from antibody B1-8, a V_λ domain, with the V_L domain from antibody NQ11, a V_κ domain, leads to a dramatic conformational change in the V_H CDR3 loop of antibody B1-8. The magnitude of this change is similar to the largest of the conformational changes observed in antibody fragments in response to antigen binding. Combinatorial pairing of V_H and V_L domains constitutes a major component of antibody diversity. Conformationally flexible antigen-binding sites capable of adapting to the specific CDR3 loop context created upon V_H–V_L pairing may be employed by the immune system to maximize the structural diversity of the immune response.     

Anorectal function in the solitary rectal ulcer syndrome

The anorectal function of nine patients with solitary rectal ulcer syndrome (SRUS) (5 F: 4 M, median age, 27 (range, 19–41 years) and nine control subjects (5 F: 4 M, median age, 47 (35–66)P<0.01) has been investigated by a new technique that radiologically visualizes the anorectum during voiding of a semisolid contrast medium, while simultaneously measuring intrarectal pressure and anal sphincter EMG activity. A degree of rectal prolapse was demonstrated in eight of the SRUS patients; six of these lesions were clinically occult. Abnormal failure of the anal sphincter to relax on voiding was present in seven of the SRUS patients. These abnormalities resulted in the SRUS patients requiring a greater increase in intrarectal pressure (median, 100 cm water) to void than the control subjects (median, 65 cm water,P<0.01). This combination of high intrarectal pressure and rectal prolapse during straining seems to be the cause of SRUS This work was supported by a grant from the Medical Research Council.