Brucellosis in a Virginia Meat-Packing Plant

In a 13-month period, June 1966 through June 1967, 45 male workers in a meat-packing plant in Virginia had clinical brucellosis, confirmed by serological evidence or isolation of Brucella organisms. All cases were related to the kill areas of the plant.

A serologic survey of personnel revealed 13 persons with titers for brucellosis but with no history of a related illness. Airflow studies using smoke candles demonstrated that the flow of air within the kill areas tended to pool at the location where the largest concentration of cases occurred; however, this area did not have the highest incidence of infection. No evidence of crossconnections or back siphonage in the plant water system was found.

Sera from 2, 275 swine (butcher hogs and sows) were tested; 4.6% were positive, with sows showing 6.1%. Six isolates of Brucella svis were made by means of air samplers and settling plates; these isolates suggests the possibility of infection by the aerosol route.     

Glycemic variability is complex - is glucose complexity variable?

Observational studies show an independent association between increased glycemic variability and higher mortality in critically ill patients. Minimization of glycemic variability is therefore suggested as a new target of glycemic control, which may require very frequent or almost continuous monitoring of glucose levels. Brunner and colleagues show the use of real-time subcutaneous continuous glucose monitoring does not decrease glycemic variability. Continuous glucose monitoring, however, may reveal changes in glucose complexity, which may be of interest since both increased and decreased glucose complexity is associated with higher mortality in the critically ill.In the previous issue of Critical Care Brunner and colleagues report on the results of a post-hoc analysis [1] of two previously published randomized controlled trials evaluating real-time subcutaneous continuous glucose monitoring (CGM) in critically ill patients [2,3]. Their main findings are that glycemic control guided by real-time CGM does not significantly reduce glycemic variability (GV) and that both increased and decreased glucose complexity is significantly associated with ICU survival and with the presence of diabetes.There is an independent association between increased GV and higher mortality in ICU patients [4,5]. GV depends on endogenous factors (for example, severity of illness) but also on exogenous factors (for example, inappropriate glucose measurement intervals and improper insulin adjustments). Minimization of GV is suggested as a new target of glycemic control [6], which may require very frequent or almost continuous monitoring of glucose levels. However, a secondary analysis of the first two Leuven studies shows that strict glycemic control, which includes frequent monitoring of the blood glucose level, does not decrease GV [7]. The present study shows that strict glycemic control using almost continuous monitoring also does not decrease GV [1].Therefore it is very difficult, if not impossible, to decrease GV. Are the nurses in Brunner and colleagues'' ICU already performing strict glycemic control so well that GV simply cannot be further decreased? Notably, the standard deviation - one of the measures of GV used by the present analysis - is already very low in the control group compared with values reported in previous studies. Nurses could also poorly or only sporadically respond to the real- time CGM results with alterations in insulin infusion, thereby losing any potential for real-time CGM to further decrease GV. We should also not forget that the present study uses subcutaneous glucose levels and not blood glucose levels for calculation of indicators of GV. Subcutaneous GV may simply not be the same as blood GV. Finally, we must keep in mind that the sample frequency per se may affect the calculation of indicators of GV. Indeed, indicators of GV may not only truly reflect GV, but may also depend on the number of measurements per time unit used for its calculation [8]. Brunner and colleagues actually confirm this dependency in their analysis of the impact of the method of glucose determination on indicators of GV [1].Less well known is that loss of glucose complexity is also associated with higher mortality of critically ill patients. Complex biological systems are characterized by a highly complex output, and one of the first symptoms of disease is decomplexification [9,10]. Well-known examples include decreased intrauterine heart rate complexity with fetal stress, and decreased heart rate and temperature complexity with severe infection. Complexity, in contrast to variability, depends on endogenous factors, and not on exogenous factors. Interestingly, progressive loss of glucose complexity is found from health through the metabolic syndrome to type II diabetes [11-14]. The results of the present study are in line with those findings, at least to some extent. They also echo the results from a previous investigation showing that loss of glucose complexity is associated with higher mortality [15]. The finding that increased glucose complexity is also associated with higher mortality, however, is new. Therefore, next to hyperglycemia, hypoglycemia and GV, glucose complexity should be seen as one new domain of glycemia (Figure ​(Figure1),1), although glucose complexity cannot be changed by titration of insulin.Open in a separate windowFigure 1Schematic view of the four domains of blood glucose control. [1] hyperglycemia, [2] hypoglycemia, [3] glycemic variability, and [4] glucose complexity. CGM, continuous glucose monitoring.As we speak, several CGM systems are being developed and clinically tested in critically ill patients. These systems all have the potential to improve performance and safety of insulin titration in the ICU. They may also improve our insights into insulin resistance and help us to better understand the impact of GV on outcome. The present study not only shows that GV does not improve with the use of CGM per se, but also suggests that we need to develop better measures of GV, independent of the sample frequency. Finally, CGM systems allow us to determine and follow changes in glucose complexity. This allows one to inspect whether glucose complexity increases (from decreased complexity) or decreases (from increased complexity) in individual patients, and to determine whether these changes follow changes in insulin resistance over time. If this indeed is the case, then CGM could even help us in decisions to start or stop strict glycemic control in individual patients, thereby preventing side effects of insulin infusion.     

Challenges to pharmacy and pharmacy practice in Pakistan

The Islamic Republic of Pakistan is the sixth most populous country in the world. While exploring the history of the development of the pharmacy profession, the author discovered that the late Sheikh Nabi Buksh was the first to start a general store with a pharmacy in 1863. After the independence of Pakistan (14 August 1947), the University of Punjab became the first institution to develop a three-year bachelor programme in 1948 which was extended to four years in 1978-1979. In 2003, a step towards further change was seen when the Higher Education Commission (HEC) upgraded its BPharm programme to a five-year Doctor of Pharmacy (PharmD) programme. At the moment the Pakistani PharmD programme is facing a number of problems which are acting as a hurdle to Pakistani pharmacists and the establishment of pharmacy practice as a profession in Pakistan. This perspective will highlight these challenges so that the HEC and the Pakistan Pharmacy Council (PPC) can intervene to modify the Pakistani healthcare system in order to establish a good foundation for practicing pharmacists and to develop strategies to cope with the challenges accordingly.     

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia

Objective

To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia.

Methods

We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence.

Findings

There were 526 pneumonia events among 10 600 children – an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses.

Conclusion

There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.     

The costs of traumatic brain injury due to motorcycle accidents in Hanoi, Vietnam

Background

Road traffic accidents are the leading cause of fatal and non-fatal injuries in Vietnam. The purpose of this study is to estimate the costs, in the first year post-injury, of non-fatal traumatic brain injury (TBI) in motorcycle users not wearing helmets in Hanoi, Vietnam. The costs are calculated from the perspective of the injured patients and their families, and include quantification of direct, indirect and intangible costs, using years lost due to disability as a proxy.

Methods

The study was a retrospective cross-sectional study. Data on treatment and rehabilitation costs, employment and support were obtained from patients and their families using a structured questionnaire and The European Quality of Life instrument (EQ6D).

Results

Thirty-five patients and their families were interviewed. On average, patients with severe, moderate and minor TBI incurred direct costs at USD 2,365, USD 1,390 and USD 849, with time lost for normal activities averaging 54 weeks, 26 weeks and 17 weeks and years lived with disability (YLD) of 0.46, 0.25 and 0.15 year, respectively.

Conclusion

All three component costs of TBI were high; the direct cost accounted for the largest proportion, with costs rising with the severity of TBI. The results suggest that the burden of TBI can be catastrophic for families because of high direct costs, significant time off work for patients and caregivers, and impact on health-related quality of life. Further research is warranted to explore the actual social and economic benefits of mandatory helmet use.     

Survival after out-of-hospital cardiac arrest,Viet Nam: multicentre prospective cohort study

ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.     

大鼠肝脏缺血再灌注损伤后5′核苷酸酶和乳酸脱氢酶活化变化的研究

目的 探讨大鼠肝脏经过UW、Celsior和HTK三种不同类型保存液低浊保存和常温再灌注后5′核苷酸酶和乳酸脱氢酶活性的变化。方法 将大鼠肝脏在UW、Celsior和HTK液中低温4℃保存0、8、16、和24h后,采用离体连续灌注模型,用Krebs-Henseleit液37℃连续循环灌注90min,灌注结束后取肝脏组织标本测定5′核苷酸酶和乳酸脱氢酶活性,并测定胆汁分泌量的变化。结果 经过16和24h的UW和Celsior低温保存后的肝组织5′核式酸酶和乳酸脱氢酶的活性出现降低;HTK组8h就出现降低,UW和Celsior组经过24h的低温保存后,胆汁分泌量开始明显;在HTK组16h后,胆汁分泌量就显著降低。结论 5′核苷酸酶和乳酸脱氢酶的活性随着低温缺血时间的延长逐渐降低;UW和Celsior液以肝窦内皮细胞和肝实质细胞的保护作用均强于HTK。     

大鼠肝脏缺血再灌注损伤后5′核苷酸酶和乳酸脱氢酶活性变化的研究

目的探讨大鼠肝脏经过UW、Celsior和HTK三种不同类型保存液低温保存和常温再灌注后5′核苷酸酶和乳酸脱氢酶活性的变化.方法将大鼠肝脏在UW、Celsior和HTK液中低温4℃保存0、8、16和24 h后,采用离体连续灌注模型,用Krebs-Henseleit液37℃连续循环灌注90 min,灌注结束后取肝脏组织标本测定5′核苷酸酶和乳酸脱氢酶活性,并测定胆汁分泌量的变化.结果经过16和24 h的UW和Celsior低温保存后的肝组织5′核苷酸酶和乳酸脱氢酶的活性出现降低;HTK组8 h就出现降低.UW和Celsior组经过24 h的低温保存后,胆汁分泌量开始明显降低;在HTK组16 h后,胆汁分泌量就显著降低.结论 5′核苷酸酶和乳酸脱氢酶的活性随着低温缺血时间的延长逐渐降低;UW和Celsior液对肝窦内皮细胞和肝实质细胞的保护作用均强于HTK.     

Cloning, chromosomal mapping and expression pattern of the mouse Brca2 gene

A proportion of human breast cancers result from an inherited predisposition to the disease. Mutations in the BRCA2 gene confer a high risk of breast cancer and are responsible for almost half of these cases. The recent cloning of the human BRCA2 gene has revealed that it encodes a large protein having little significant homology to known proteins. Here we describe the mouse Brca2 gene. The gene maps to mouse chromosome 5, consistent with its location on human chromosome 13q12. We have sequenced cDNA for the entire 3329 amino acid Brca2 protein and this has revealed that, like Brca1, Brca2 is relatively poorly conserved between humans and mice. Brca2 is transcribed in a diverse range of mouse tissues, and the pattern of expression is strikingly similar to that of Brca1. Taken together, our data highlight some intriguing similarities between two genes involved in inherited breast cancer susceptibility.