Why are US military personnel prescribed transdermal fentanyl patches?

INTRODUCTION: Transdermal fentanyl is a continuous release opioid delivery system intended for use in opioid-tolerant patients requiring around-the-clock opioid therapy. The purpose of this study is to identify the most common indications for transdermal fentanyl prescriptions in active duty US military personnel, and determine whether these prescriptions meet US Food and Drug Administration (FDA) labelling. METHODS: Active duty US military personnel initiating transdermal fentanyl therapy with prescriptions filled at Military Health System pharmacies between 2015 and 2019 were identified in the Military Data Repository. Electronic health records were searched for patient demographic information, clinical information and prescription data. A total of 225 patients with complete data were identified. RESULTS: The most common reason for transdermal fentanyl initiation was chronic non-cancer musculoskeletal pain. Among patients with non-cancer pain, 36% received their initial prescription from an internal medicine/primary care provider, and 35% did not meet published US FDA criteria for opioid tolerance prior to treatment initiation. There was an 81% decrease in patients initiating therapy between 2015 and 2019. CONCLUSIONS: While a substantial minority of transdermal fentanyl prescriptions to US military personnel did not meet FDA guidelines on appropriate use, the overall number of prescriptions fell dramatically over the study period. This suggests that automated profile review or additional targeted policies to limit transdermal fentanyl prescribing are unnecessary at this time.

How Children Learn to Navigate the Symbolic World of Pictures: The Importance of the Artist's Mind and Differentiating Picture Modalities.

Pictures offer a unique and essential contribution to our lives, both in terms of aesthetic pleasure and links to symbolic thought. As such, psychologists have devoted significant time to investigating how children acquire an understanding of pictures. This chapter focuses on two particular facets of this development: the role of the artist and the importance of picture modality. First, we review work that has focused on tracking children's ability to (a) map the relationship between the mental state of the artist and their pictures, and (b) incorporate such considerations into their evaluations of pictures. Drawing these literatures together provides an up-to-date account of how children acquire a mentalistic understanding of pictures. Second, we argue that a mature theory of pictures must enable children to distinguish between different picture types (e.g., photographs vs drawings), and therefore that picture modality should be incorporated into existing theoretical accounts of pictorial development.

Safety of sedation for gastrointestinal endoscopy in a group of university-affiliated hospitals: a prospective cohort study.

BACKGROUND: Service models for gastrointestinal endoscopy sedation must be safe, as endoscopy is the most common procedure performed under sedation in many countries. The aim of this prospective cohort study was to determine the patient risk profile, and incidence of and risk factors for significant unplanned events, in adult patients presenting for gastrointestinal endoscopy in a group of university-affiliated hospitals where most sedation is managed by anaesthetists. METHODS: Patients aged ≥18 yr presenting for elective and emergency gastrointestinal endoscopy under anaesthetist-managed sedation at nine hospitals affiliated with the University of Melbourne, Australia, were included. Outcomes included significant airway obstruction, hypoxia, hypotension and bradycardia; unplanned tracheal intubation; abandoned procedure; advanced life support; prolonged post-procedure stay; unplanned over-night admission and 30-day mortality. RESULTS: 2,132 patients were included. Fifty percent of patients were aged >60 yr, 50% had a BMI >27 kg m -2, 42% were ASA physical status III-V and 17% were emergency patients. The incidence of significant unplanned events was 23.0% (including significant hypotension 11.8%). Significant unplanned intraoperative events were associated with increasing age, BMI <18.5 kg m -2, ASA physical status III-V, colonoscopy and planned tracheal intubation. Thirty-day mortality was 1.2% (0.2% in electives and 6.0% in emergencies) and was associated with ASA physical status IV-V and emergency status. CONCLUSIONS: Patients presenting for gastrointestinal endoscopy at a group of public university-affiliated hospitals where most sedation is managed by anaesthetists, had a high risk profile and a substantial incidence of significant unplanned intraoperative events and 30-day mortality.

Survey of anaesthetists' practice of sedation for gastrointestinal endoscopy.

We conducted a survey of Australian specialist anaesthetists about their practice of sedation for elective and emergency gastroscopy, endoscopic retrograde cholangiopancreatography (ERCP), and colonoscopy. A 24-item survey was emailed to 1,000 anaesthetists in August 2015. Responses were received from 409 anaesthetists (response rate=41%) with responses from 395 anaesthetists analysed. Pulse oximetry and oxygen administration were routine for all procedures for all respondents. Blood pressure was routinely measured by most respondents during gastroscopy (elective=88%; emergency=97%), ERCP (elective=99%; emergency=99%) and colonoscopy (elective=91%; emergency=98%). The airway was routinely managed with jaw lift or oral or nasal airway by 99%, 76% and 97% of respondents during gastroscopy, ERCP and colonoscopy, whereas in emergency procedures endotracheal intubation was routine in 49%, 64% and 17% of procedures. Propofol was routinely administered by 99% of respondents for gastroscopy and 100% of respondents for ERCP and colonoscopy. A maximum depth of sedation in which patients were unresponsive to painful stimulation was targeted by the majority of respondents for all procedures except for elective gastroscopy. These results may be used to facilitate comparison of practice in Australia and overseas, and give an indication of compliance by Australian anaesthetists with the relevant Australian and New Zealand College of Anaesthetists guideline.

Validation of the postoperative nausea and vomiting intensity score in gynaecological patients.

The Postoperative Nausea and Vomiting (PONV) Intensity Scale was developed to distinguish trivial from clinically important PONV perioperatively and has been validated in a general surgical population. This study aimed to assess the scale in gynaecological surgery patients. Seventy-three patients undergoing gynaecological surgery were included. Interviews occurred at four and 24 hours postoperatively. Measurements included the PONV Intensity Scale, nausea and pain visual analogue scale, antiemetic use and complications related to PONT. Ten patients (14%) had a clinically significant PONV Intensity Scale score, 42 (58%) reported nausea and 15 (21%) reported vomiting during the study. At 24 hours, 80% of patients with a clinically significant score at four hours had received antiemetics vs 18% of those without a clinically significant score (P = 0.001). Of patients with a clinically significant score at 24 hours, 71% had suffered a complication vs 11% of those without a clinically significant score (P < 0.0001). The median nausea visual analogue scale scores at four hours were 69 mm (interquartile range 69 to 76 mm) in patients with a clinically significant score vs 0 mm (0 to 9 mm) in patients without a clinically significant score (mean difference 56 mm, 95% confidence interval 41 to 72 mm, P < 0.0001). The PONV Intensity Scale is a valid, responsive and practically useful instrument in distinguishing trivial from clinically significant PON. The rate of clinically important PONV is considerably lower than the rate of any PONV symptoms perioperatively.

Development and utilization of transgenic New World screwworm, Cochliomyia hominivorax.

The New World screwworm (NWS), Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), was the first insect to be effectively controlled using the sterile insect technique (SIT). Recent efforts to improve SIT control of this species have centred on the development of genetically transformed strains using the piggyBac transposon vector system. Eight transgenic strains were produced incorporating an enhanced green fluorescent protein (EGFP) marker gene under polyubiquitin regulation that has the potential for use as a genetic marking system for released males. The transgenic strains were genetically and phenotypically characterized, including for life fitness parameters and mating competitiveness. These characteristics were unique for each strain and thus some strains were deemed suitable for incorporation into SIT eradication programmes. The strain with the best attributes is designated 'CLAY'. Four of the strains, including CLAY, have been successfully cryopreserved so that their original characteristics should be unchanged when further evaluation is required. With the demonstration of efficient germ-line transformation in NWS, allowing production of fit and competitive transformants, it is now possible to consider further transgenic strain development to improve SIT that are currently being tested in other dipteran species. This includes strains that allow genetic marking with fluorescent proteins, genetic sexing by female lethality, male-specific fluorescent sorting and male sterility by testis-specific lethality. The SIT may also be improved upon by new strategies resulting in lethality of offspring of released insects using conditional lethal systems based upon temperature-dependent or dietary tetracycline regulation of lethal gene expression. Both the creation of new NWS transgenic strains and the ecological safety of their release will be enhanced by new vector systems that allow specific genomic targeting of vector constructs and their subsequent immobilization, ensuring transgene and strain stability.

Repellency of callicarpenal and intermedeol against workers of imported fire ants (Hymenoptera: Formicidae).

Callicarpenal and intermedeol are two insect-repellent terpenoids isolated from leaves of American beautyberry (Callicarpa americana L.; Verbenaceae) and Japanese beautyberry (Callicarpa japonica Thunb.). The repellency of these two terpenoids against workers of red imported fire ants, Solenopsis invicta Buren, black imported fire ants, Solenopsis richteri Forel, and a hybrid of these two species was evaluated using digging bioassays. In a multiple choice digging bioassay using two colonies from each species and their hybrid, callicarpenal showed significant repellency at concentration as low as 50 ppm against both red imported fire ant colonies and 6.25 ppm against all black imported fire ant and hybrid colonies. Intermedeol showed significant repellency at concentration as low as 1.50 ppm against both red imported fire ant colonies and 6.25 ppm against all black imported fire ant and hybrid colonies. In total, 15 colonies, five colonies from each species and the hybrid, were tested on callicarpenal and intermedeol at 50 ppm in a two-choice digging bioassay. Both callicarpenal and intermedeol showed repellency against all colonies, and intermedeol showed significantly greater repellency than callicarpenal against both species and their hybrid.

Expressed sequenced tags from Lygus lineolaris (Hemiptera: Miridae), the tarnished plant bug.

Expressed sequenced tags (ESTs) were prepared to establish a baseline for molecular genetic studies of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois). The largest class of identifiable ESTs (15.2%) was from genes involved in cellular metabolic functions, including physiological processes. Twenty-seven ESTs (9.8%) were from genes associated with transcription and translation, including ribosomal genes. One hundred and forty-two of the 276 unique ESTs were from genes not previously identified from any organism. Twelve sequences appear to be associated with feeding and digestion and may be targets for pest control studies.

Expressed sequenced tags from Lygus lineolaris (Hemiptera: Miridae), the tarnished plant bug

Expressed sequenced tags (ESTs) were prepared to establish a baseline for molecular genetic studies of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois). The largest class of identifiable ESTs (15.2%) was from genes involved in cellular metabolic functions, including physiological processes. Twenty-seven ESTs (9.8%) were from genes associated with transcription and translation, including ribosomal genes. One hundred and forty-two of the 276 unique ESTs were from genes not previously identified from any organism. Twelve sequences appear to be associated with feeding and digestion and may be targets for pest control studies

Significance of digging behavior to mortality of red imported fire ant workers, Solenopsis invicta, in fipronil-treated sand.

The effect of fipronil-treated sand on digging behavior and mortality of red imported fire ant, Solenopsis invicta Buren, workers was examined in the laboratory. No-choice digging bioassays where fipronil-treated sand was the only available digging substrate were conducted on two colonies at fipronil concentrations of 0.00, 0.05, 0.10, 0.50, 1.00, 1.50, and 2.00 ppm. Workers dug into the fipronil-treated sand in all cases, even at 2.0 ppm level, which caused 100% mortality in acute toxicity tests for both colonies. At 1.5 and 2.0 ppm, workers from the less sensitive colony had significantly higher mortality than those from the more sensitive colony, which might be explained by the significantly higher digging activity of the less sensitive colony. In two-choice digging bioassays where untreated sand was also available, workers dug into the fipronil-treated sand in 29 of 30 cases, even at 10.0 ppm level. At 1.0 and 10.0 ppm, mortality was positively correlated to digging effort in treated sand; however, such correlation was significant only at 1.0 ppm level. This indicates that digging did affect mortality; however, such effect is concentration dependent.

piggyBac transformation of the New World screwworm, Cochliomyia hominivorax, produces multiple distinct mutant strains.

Sterile insect technique (SIT) programs are designed to eradicate pest species by releasing mass-reared, sterile insects into an infested area. The first major implementation of SIT was the New World Screwworm Eradication Program, which successfully eliminated the New World screwworm (NWS), Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), from the Continental US, Mexico and much of Central America. Ionizing radiation is currently used for sterilization, but transgenic insect techniques could replace this method, providing a safer, more cost-effective alternative. Genetic transformation methods have been demonstrated in NWS, and verified by Southern blot hybridization, PCR and sequencing of element insertion junctions. A lethal insertional mutation and enhancer detection-like phenotypic expression variations are presented and discussed. In addition to supporting the eradication efforts, transformation methods offer potential means to identify genes and examine gene function in NWS.

Growth hormone enhances proinflammatory cytokine production by monocytes in whole blood.

Growth hormone (GH) has been used as anabolic therapy to treat catabolic patients. In a recent study, however, administration of high doses of GH to critically ill adults was associated with an increase in morbidity and mortality. Preponderance of septic shock and uncontrolled infections as causes of death in these patients suggests an immuno-modulatory effect of GH. Our hypothesis was that GH treatment may modulate the production of proinflammatory cytokines, which are implicated in sepsis. In our study, human monocytes in whole blood were activated with lipopolysaccaharide (LPS) (1-100 ng/ml) purified from a clinical isolate of group B Neisseria meningitidis in the presence of a high dose of GH (100 ng/ml). The subsequent proinflammatory cytokine response was analysed by intracellular cytokine staining and flow cytometry. Our results show that GH enhances IL1-alpha, IL-6 and TNF-alpha production by LPS activated monocytes in whole blood. The modulation of cytokines by GH may be responsible for the adverse consequences of GH in critically ill patients.

Stable, germ-line transformation of Culex quinquefasciatus (Diptera: Culicidae).

A Hermes-based transposable element transformation system incorporating an enhanced green fluorescent protein (EGFP) marker was used to produce two transgenic lines of Culex quinquefasciatus (Say). The transformation frequency was approximately 12% and transformation of Culex was shown to be dependent on the presence of Hermes transposase. Injected Culex embryos were treated with four different heat shock regimes, two of which produced transformed individuals. These individuals were mated with wild-type mosquitoes and produced offspring which expressed the dominant EGFP gene in Mendelian ratios predicted for the stable integration of a gene at a single locus. The two transformed lines displayed distinct patterns of phenotypic expression, the expression of which has remained stable after fifteen generations. In these transgenic lines both the Hermes element and flanking plasmid DNA integrated into the Culex genome, as has been previously seen in Hermes-mediated transgenic strains of Aedes aegypti (L.). The high frequency of Culex transformation together with the dependence on the presence of Hermes transposase suggests that, as for Ae. aegypti, this mode of transposition into the germ-line genome occurs by an alternate mechanisms to the cut and paste type of transposition seen for this element in other insect species and in the somatic nuclei of mosquitoes. This is the first report of the genetic transformation of a species in the genus Culex and demonstrates that this medically important mosquito species can now, along with several other Culicine and Anopheline mosquito species, be genetically manipulated.

The comparison of midazolam and topical lidocaine spray versus the combination of midazolam, meperidine, and topical lidocaine spray to sedate patients for upper endoscopy.

BACKGROUND: Whether an opiate-benzodiazepine combination is superior to benzodiazepine alone for sedation in upper endoscopy is controversial. The purpose of this study was to compare the effectiveness of intravenous midazolam alone versus the combination of intravenous midazolam and intravenous meperidine for the sedation of patients undergoing upper endoscopy. METHODS: One hundred seven patients scheduled for outpatient diagnostic esophagogastroduodenoscopy were randomly assigned to receive 50 mg intravenous meperidine (53 of 107) or placebo (54 of 107). All patients received topical lidocaine spray and as much midazolam as the endoscopist thought the patient needed. Patients and endoscopists were blinded as to assignment. Data collected included intubation time (seconds), procedure time (minutes), pulse, blood pressure, complications, and the need for reversal agents. The endoscopist evaluated the quality of sedation immediately after the procedure (1 = excellent, 2 = good, 3 = fair, and 4 = poor). The patient evaluated the procedure the next day by phone (1 = no discomfort or did not remember, 2 = slightly uncomfortable, 3 = extremely uncomfortable, and 4 = unacceptable). Patients were also asked whether they would agree to another esophagogastroduodenoscopy if their doctor thought it was medically necessary. RESULTS: The intubation time, procedure time and blood pressure were not significantly different between the 2 groups. In comparing the meperidine group versus placebo group, the highest pulse (82.3 vs. 93.7, p = 0.0010), lowest pulse (67.2 vs. 72.3, p = 0.0194) and amount of midazolam used (4.0 vs. 4.8 mg, p = 0.0185 or 0.53 vs. 0.67 mg/kg, p = 0.0083) were significantly different by using a t test analysis. Patient evaluations comparing meperidine versus placebo showed responses of 1 (52 vs. 49), 2 (1 vs. 3), 3 (0 vs. 2) and 4 (0 vs. 0), which were not significantly different. The endoscopists'evaluation comparing meperidine versus placebo gave responses of excellent (44 vs. 27), good (6 vs. 22), fair (3 vs. 5) and poor (0 vs. 0), which were highly significantly different (p < 0.001) by using chi-square statistical techniques. CONCLUSION: The addition of meperidine to midazolam in sedating patients undergoing upper endoscopy adds no benefit from the patient viewpoint, whereas endoscopists favored the use of both medications.

End expiration is more accurate than mid respiration in measuring lower esophageal sphincter pressure.

BACKGROUND/AIMS: Two ways popularly used to measure lower esophageal sphincter pressure are the mid-respiratory and end-expiratory methods. The aim of this study was to compare the suitability of these methods in the manometric assessment of patients with endoscopically documented esophagitis. METHODS: Manometry was performed on 22 consecutive patients to determine whether medical therapy or surgery was the more appropriate treatment strategy. Lower esophageal sphincter pressure was measured during a slow station pull-through. End-expiratory lower esophageal sphincter pressure was assessed by measuring the highest trough which coincided with end expiration. Mid-respiratory lower esophageal sphincter pressure was assessed by bracketing the highest pressure over >/=3 respiratory cycles and measuring the mid point. RESULTS: Mid-respiratory lower esophageal sphincter pressure (25.6 mm Hg) was higher (p < 0.0001) than end-expiratory lower esophageal sphincter pressure (15.7 mm Hg). Nine (41%) end-expiratory lower esophageal sphincter pressures were abnormally low (i.e., <10 mm Hg), whereas three (14%) mid-respiratory lower esophageal sphincter pressures were abnormally low (i.e., <14 mm Hg; p = 0.042). CONCLUSIONS Mid-respiratory lower esophageal sphincter pressure measurement includes respiratory artifact and does not accurately measure lower esophageal sphincter pressure. End-expiratory sphincter pressure better identifies potential surgical candidates.