Improved Pharmacy Department Workflow with New Method of Order Entry for Single-Agent,High-Dose Methotrexate

Purpose:

To determine whether a process change impacted the proportion of orders for single-agent, high-dose methotrexate entered by chemotherapy pharmacists instead of general pharmacy staff. Coordination of antiemetic premedication and leucovorin rescue with the new method of order entry was evaluated.

Methods:

Adults treated with single-agent, high-dose methotrexate were identified retrospectively. Order entry of methotrexate and ancillary medications was examined to determine whether the old or new method was used and whether it was performed by a chemotherapy pharmacist. The fundamental difference between the old and new methods for order entry is use of the “unscheduled” frequency of medication administration to replace the administration frequency of “once” with a specified date and time. Timing of antiemetic premedication and leucovorin rescue relative to methotrexate administration were tallied for the new method. Chi-square analysis was performed for the primary objective. Observational statistics were performed otherwise.

Results:

The number of evaluable encounters identified was 158. A chemotherapy pharmacist entered a greater proportion of orders when the new method was utilized (P < .0001). The proportion of orders entered by a chemotherapy pharmacist increased during the hours of 0700 and 2259 with the new method. Appropriate coordination of antiemetic and leucovorin administration was documented for 96% and 100% of cases with the new method of order entry.

Conclusion:

The proportion of orders for single-agent, high-dose methotrexate entered by a chemotherapy pharmacist was significantly greater with the use of the new method. Administration of antiemetic premedication and leucovorin rescue were appropriately coordinated with the use of the new method for order entry of single-agent, high-dose methotrexate.     

Electricians’ chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer

Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians’ exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen.     

Risk factors for tuberculosis in older children and adolescents: a matched case–control study in Recife,Brazil

Background

Tuberculosis is a major disease worldwide and most research focus on risk factors for adults, although there is a marked adolescent peak in incidence. The objective of this study was to identify risk factors for tuberculosis in children aged 7 to 19.

Methods

A case control study matched by age with 169 cases and 477 controls. The study population consisted of adolescents and older children from Recife, Brazil. Cases were individuals diagnosed with tuberculosis in the control programme and controls were selected in the neighborhood of cases. Conditional logistic regression was used to identify risk factors.

Results

Cigarette smoking increased by 50% the risk of tuberculosis but that this was not statistically significant (OR?=?1.6). Other risk factors were sleeping in the same house as a case of tuberculosis (OR?=?31.6), living in a house with no piped water (OR?=?7.7) (probably as a proxy for bad living conditions), illiteracy (OR?=?3.7) and male sex (OR?=?1.8). The increase in risk with living in houses with no piped water was much more marked in males. The proportion of cases of tuberculosis attributed to contact with someone with TB was 38% and to illiteracy, lack of piped water and smoking, 20%.

Conclusion

Household contact with tuberculosis, social factors and male sex play the biggest role in determining risk of TB disease among children and adolescents in the study. We recommend further research on the relationship of cigarette smoking on tuberculosis in adolescents, and on whether the sex differentials are more marked in bad living conditions. Separate studies should be conducted in older children and in adolescents.

     

Psychische Gesundheit von übergewichtigen und adipösen Jugendlichen unter Berücksichtigung von Sozialstatus und Schulbildung

Background

International studies showed that overweight and obese adolescents are more likely to have mental health problems compared to normal weight peers.

Objectives

This study analyses the relation between overweight/obesity and mental health problems among adolescents in Germany as well as potential modifying factors of this relation.

Materials and Methods

Data base was a subsample of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS, n?=?6,813, 11–17 years) which was conducted by the Robert Koch Institute from May 2003 to May 2006. Body height and weight were measured in a standardised manner and body mass index (BMI) was calculated. Indications of mental health problems and strengths were collected with the Strengths and Difficulties Questionnaire (SDQ) in the following areas: emotional symptoms, conduct problems, hyperactivity, peer relationship problems and prosocial behaviour. Socio-economic status (SES) and education are analysed as modifying variables. Prevalence and odds ratios with 95?% confidence intervals were calculated by binary logistic regression.

Results

Obese boys and overweight and obese girls showed more indications of mental health problems compared to normal weight peers. The most common problem areas were conduct problems and peer relationship problems. Obese girls were also more likely to show indications of emotional symptoms compared to normal weight girls. The age stratified analysis showed that the differences in the occourrence of mental health problems between normal weight and obese boys as well as between normal weight and overweight/obese girls are more pronounced aged 11 to 13 years than aged 14 to 17 years. The results on the impact of SES and education showed that in girls, SES had a modyfying impact on the relation between overweight/obesity and mental health problems in favour of the high SES group. In boys, SES only had a modifying impact on the relation between overweight and mental health problems, but here in favour of the low SES group. Only in girls education had a modifying impact on the relation between obesity and mental health problems in favour of the low education group.

Conclusion

In adolescence, overweight and especially obesity go along with a higher risk for mental health problems. In the context of prevention measures and care services for overweight and obesity at a young age, psychosocial aspects should be considered.     

Pharmacological Stimulation of the Brain Serotonin Receptor 7 as a Novel Therapeutic Approach for Rett Syndrome

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG-binding protein 2 gene (MECP2) cause >95% of classic cases, and currently there is no cure for this devastating disorder. The serotonin receptor 7 (5-HT7R) is linked to neuro-physiological regulation of circadian rhythm, mood, cognition, and synaptic plasticity. We presently report that 5-HT7R density is consistently reduced in cortical and hippocampal brain areas of symptomatic MeCP2–308 male mice, a RTT model. Systemic repeated treatment with LP-211 (0.25 mg/kg once/day for 7 days), a brain-penetrant selective 5-HT7R agonist, was able to rescue RTT-related defective performance: anxiety-related profiles in a Light/Dark test, motor abilities in a Dowel test, the exploratory behavior in the Marble Burying test, as well as memory in the Novelty Preference task. In the brain of RTT mice, LP-211 also reversed the abnormal activation of PAK and cofilin (key regulators of actin cytoskeleton dynamics) and of the ribosomal protein (rp) S6, whose reduced activation in MECP2 mutant neurons by mTOR is responsible for the altered protein translational control. Present findings indicate that pharmacological targeting of 5-HT7R improves specific behavioral and molecular manifestations of RTT, thus representing a first step toward the validation of an innovative systemic treatment. Beyond RTT, the latter might be extended to other disorders associated with intellectual disability.     

The equal right to drink

The starting place for this essay is Knupfer and Room's insight that more restrictive norms around drinking and intoxication tend to be selectively applied to the economically dependent segments of society, such as women. However, since these authors wrote in 1964, women in the US and many other societies around the globe have experienced rising economic independence. The essay considers how the moral categories of acceptable drinking and drunkenness may have shifted alongside women's rising economic independence, and looks at evidence on the potential consequences for women's health and wellbeing. I argue that, as women have gained economic independence, changes in drinking norms have produced two different kinds of negative unintended consequences for women at high and low extremes of economic spectrum. As liberated women of the middle and upper classes have become more economically equal to men, they have enjoyed the right to drink with less restraint. For them, alongside the equal right to drink has come greater equality in exposure to alcohol‐attributable harms, abuse and dependence. I further suggest that, as societies become more liberated, the economic dependency of low‐income women is brought into greater question. Under such conditions, women in poverty—particularly those economically dependent on the state, such as welfare mothers—have become subject to more restrictive norms around drinking and intoxication, and more punitive social controls. [Schmidt LA. The equal right to drink. Drug Alcohol Rev 2014;33:581–7]     

High Magnesium and Sirolimus on Rabbit Vascular Cells—An In Vitro Proof of Concept

Drug-eluting bioresorbable scaffolds represent the last frontier in the field of angioplasty and stenting to treat coronary artery disease, one of the leading causes of morbidity and mortality worldwide. In particular, sirolimus-eluting magnesium-based scaffolds were recently introduced in clinical practice. Magnesium alloys are biocompatible and dissolve in body fluids, thus determining high concentrations of magnesium in the local microenvironment. Since magnesium regulates cell growth, we asked whether high levels of magnesium might interfere with the antiproliferative action of sirolimus. We performed in vitro experiments on rabbit coronary artery endothelial and smooth muscle cells (rCAEC and rSMC, respectively). The cells were treated with sirolimus in the presence of different concentrations of extracellular magnesium. Sirolimus inhibits rCAEC proliferation only in physiological concentrations of magnesium, while high concentrations prevent this effect. On the contrary, high extracellular magnesium does not rescue rSMC growth arrest by sirolimus and accentuates the inhibitory effect of the drug on cell migration. Importantly, sirolimus and magnesium do not impair rSMC response to nitric oxide. If translated into a clinical setting, these results suggest that, in the presence of sirolimus, local increases of magnesium concentration maintain normal endothelial proliferative capacity and function without affecting rSMC growth inhibition and response to vasodilators.     

N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection

Seneca Valley virus (SVV) is a picornavirus with potency in selectively infecting and lysing cancerous cells. The cellular receptor for SVV mediating the selective tropism for tumors is anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein expressed in tumors. Similar to other mammalian receptors, ANTXR1 has been shown to harbor N-linked glycosylation sites in its extracellular vWA domain. However, the exact role of ANTXR1 glycosylation on SVV attachment and cellular entry was unknown. Here we show that N-linked glycosylation in the ANTXR1 vWA domain is necessary for SVV attachment and entry. In our study, tandem mass spectrometry analysis of recombinant ANTXR1-Fc revealed the presence of complex glycans at N166, N184 in the vWA domain, and N81 in the Fc domain. Symmetry-expanded cryo-EM reconstruction of SVV-ANTXR1-Fc further validated the presence of N166 and N184 in the vWA domain. Cell blocking, co-immunoprecipitation, and plaque formation assays confirmed that deglycosylation of ANTXR1 prevents SVV attachment and subsequent entry. Overall, our results identified N-glycosylation in ANTXR1 as a necessary post-translational modification for establishing stable interactions with SVV. We anticipate our findings will aid in selecting patients for future cancer therapeutics, where screening for both ANTXR1 and its glycosylation could lead to an improved outcome from SVV therapy.