A case of unprovoked venous thromboembolism in a marathon athlete presenting atypical sequelae: What are the chances?

Marathon runners are exposed to multiple thrombogenic risk factors including dehydration and hemoconcentration, injury and inflammation, long-distance travel between events, and contraceptive usage. However, despite awareness about thromboembolism and several case reports detailing life-threatening hypercoagulopathies in athletes, the prevalence of venous thromboembolism in marathon runners remains uncharted. There is a lack of data and evidence-based guidelines for these athletes and for healthcare providers, including general medical practitioners and sports physicians. We present an episode of unprovoked deep vein thrombosis (DVT) and pulmonary embolism (PE) in a female marathon athlete who presented with atypical sequelae over the course of 8 months, and identify some "easy-to-miss" warning signs and symptoms. Through dialogue with the patient regarding their personal questions and anxieties surrounding idiopathic DVT-PE, we identify a clear need for more accessible information and comprehensive research concerning the detection, prevalence, and long-term management of venous thromboembolism in athletes. We discuss the possibility that being an athlete might constitute a more significant risk factor for venous thromboembolism than is currently estimated by commonly used diagnostic protocols and conclude that there is quite possibly a need for more specific clinical guidelines for athletes in this area.

A pilot improvement project in hospital-based oral healthcare: improving caries risk assessment documentation.

OBJECTIVE: To evaluate the impact of a continuous improvement project to improve completion of a caries risk assessment (CRA) and to assess its impact on delivery of dental caries prevention. DESIGN: Single centre clinical improvement project. SETTING: A paediatric dental department within a UK dental hospital over the course of 2008-2009.Subjects (materials) and methods Continuous monitoring of documentation of a CRA was instigated and results fed back to clinicians. Tools were developed to structure the process of CRA. After six months of intervention, a comparison of preventive care to a pre-intervention sample was undertaken. MAIN OUTCOME MEASURES: The main outcome measure was completion of a CRA. Comparison was also made with pre-intervention data on levels of preventive care received. RESULTS: Over the 12 month project the mean rate of CRA completion improved from 30% over the first 6 months to 73% in the second 6 months. Compared to the pre-intervention sample, all items of the caries prevention package had improved, with delivery of toothpaste strength advice (16% vs 60%, p = 0.001) and diet advice (32% vs 70%, p = 0.004) improving significantly. CONCLUSION: By targeting and improving CRA completion the quality of preventive care delivered has also significantly improved.

Pediatric electrocardiograph abnormalities following Centruroides limpidus tecomanus scorpion envenomation.

Scorpionism is an endemic public health problem in Mexico [Hoffmann, C.C., 1936. La distribucion geografica de los alacranes peligrosos en la Republica Mexicana. Bol. Inst. Hygiene Mex. 2, 321; Hoffmann, C.C., Nieto, D.R., 1939. Segunda contribucion al conocimiento de los alacranes mexicanos. Anal. Inst. Biol. 10, 83-92; Mazzoti, L., Bravo-Becherelle, M.A., 1963. Scorpionism in the Mexican Republic. In: Keegan, H.L., McFarlane, W.V. (Eds.), Venomous and Poissonous Animals and Noxious Plants of the Pacific Area. Pergamon Press, London, pp. 119-131; Monroy-Velasco, J., 1961. Alacranes venenosos de Mexico. Rev. Mex. Cien. Med. Biol., Mex. 1, 1-23; Diaz-Najera, A., 1975. Listas y datos de distribucion geografica de los alacranes de Mexico. Rev. Inv. Salud. Publica. (Mex.) 35, 1; Velasco-Castrejon, O., Lara-Aguilera, R., Alatorre, H., 1976. Aspectos epidemiologicos y clinicos de la picadura de alacran en una area hiperendemica. Rev. Inv. Salud Publica. (Mex.) 36, 93-103; Dehesa-Davila, M., Possani, L.D., 1994. Scorpionism and serotherapy in Mexico. Toxicon 32 (9), 1015-1018]. In this prospective study, we assess cardiovascular disorders in children via electrocardiographic (ECG) recordings following envenomation by scorpion species Centruroides limpidus tecomanus found in the state of Colima, Mexico. We analyzed 113 cases between the ages of 5 and 14 years. Among the most frequent symptoms presented included local pain (99.1%) and paresthesia (75.2%), pruritus (36.3%), sialorrhoea (35.4%), and nystagmus (24.8%). Cardiovascular disorders were observed in 39.8% of cases, 71% of which were rhythm abnormalities. We find a significant association between the frequency of ECG alterations and age, whereby 8-9-year-old children are more likely to experience ECG alterations when compared with other tested age groups.

Statistical process control as a tool for research and healthcare improvement.

Improvement of health care requires making changes in processes of care and service delivery. Although process performance is measured to determine if these changes are having the desired beneficial effects, this analysis is complicated by the existence of natural variation-that is, repeated measurements naturally yield different values and, even if nothing was done, a subsequent measurement might seem to indicate a better or worse performance. Traditional statistical analysis methods account for natural variation but require aggregation of measurements over time, which can delay decision making. Statistical process control (SPC) is a branch of statistics that combines rigorous time series analysis methods with graphical presentation of data, often yielding insights into the data more quickly and in a way more understandable to lay decision makers. SPC and its primary tool-the control chart-provide researchers and practitioners with a method of better understanding and communicating data from healthcare improvement efforts. This paper provides an overview of SPC and several practical examples of the healthcare applications of control charts.

Controlled site-selective protein glycosylation for precise glycan structure-catalytic activity relationships.

Glycoproteins occur naturally as complex mixtures of differently glycosylated forms which are difficult to separate. To explore their individual properties, there is a need for homogeneous sources of carbohydrate-protein conjugates and this has recently prompted us to develop a novel method for the site-selective glycosylation of proteins. The potential of the method was illustrated by site-selective glycosylations of subtilisin Bacillus lentus (SBL) as a model protein. A representative library of mono- and disaccharide MTS reagents were synthesized from their parent carbohydrates and used to modify cysteine mutants of SBL at positions 62 in the S2 site, 156 and 166 in the S1 site and 217 in the S1' site. These were the first examples of preparations of homogeneous neoglycoproteins in which both the site of glycosylation and structure of the introduced glycan were predetermined. The scope of this versatile method was expanded further through the combined use of peracetylated MTS reagents and careful pH adjustment to introduce glycans containing different numbers of acetate groups. This method provides a highly controlled and versatile route that is virtually unlimited in the scope of the sites and glycans that may be conjugated, and opens up hitherto inaccessible opportunities for the systematic determination of the properties of glycosylated proteins. This potential has been clearly demonstrated by the determination of detailed glycan structure-hydrolytic activity relationships for SBL. The 48 glycosylated CMMs formed display kcat/KM values that range from 1.1-fold higher than WT to 7-fold lower than WT. The anomeric stereochemistry of the glycans introduced modulates changes in kcat/KM upon acetylation. At positions 62 and 217 acetylation enhances the activity of alpha-glycosylated CMMs but decreases that of beta-glycosylated. This trend is reversed at position 166 where, in contrast, acetylation enhances the kcat/KMs of beta-glycosylated CMMs but decreases those of alpha-glycosylated. Consistent with its surface exposed nature changes at position 156 are more modest, but still allow control of activity, particularly through glycosylation with disaccharide lactose.

Site-selective glycosylation of subtilisin Bacillus lentus causes dramatic increases in esterase activity.

Using site directed mutagenesis combined with chemical modification, we have developed a general and versatile method for the glycosylation of proteins which is virtually unlimited in the scope of proteins and glycans that may be conjugated and in which the site of glycosylation and the nature of the introduced glycan can be carefully controlled. We have demonstrated the applicability of this method through the synthesis of a library of 48 glycosylated forms of the serine protease subtilisin Bacillus lentus (SBL) as single, pure species. As part of our ongoing program to tailor the activity of SBL for use in peptide synthesis, we have screened these enzymes for activity against the esterase substrate succinyl-Ala-Ala-Pro-Phe-S-benzyl. Gratifyingly, 22 enzymes displayed greater than wild type (WT) activity. Glycosylation at positions 62, in the S2 pocket, resulted in five glycosylated forms of SBL that were 1.3- to 1.9-fold more active than WT. At position 217, in the S1' pocket, all glycosylations increased kcat/KM up to a remarkable 8.4-fold greater than WT for the glucosylated enzyme L217C-S-beta-Glc(Ac)3. Furthermore, the ratio of amidase to esterase activity, (kcat/KM)esterase/(kcat/KM)amidase (E/A), is increased relative to wild type for all 48 glycosylated forms of SBL. Again, the most dramatic changes are observed at positions 62 and 217 and L217C-S-beta-Glc(Ac)3 has an E/A that is 17.2-fold greater than WT. The tailored specificity and high activity of this glycoform can be rationalized by molecular modeling analysis, which suggests that the carbohydrate moiety occupies the S1' leaving group pocket and enhances the rate of deacylation of the acyl-enzyme intermediate. These glycosylated enzymes are ideal candidates for use as catalysts in peptide synthesis as they have greatly increased (kcat,KM)esterase and severely reduced (kcat/KM)amidase and will favor the formation of the amide bond over hydrolysis.

Marking progress through data tracking.

In July 1997, Provider ran an overview of the foundation for continuous quality improvement (CQI). The following CQI principles were discussed: listening to customers; focusing on the processes that produce outcomes for customers; and using data to make decisions. The July article covered the first two aspects of CQI. In this article, the third principle, using data to make decisions, will be explored in further detail.