Adaptation and evaluation of a child-friendly patient reported outcome measure for use in Australia

BackgroundUse of Patient Reported Outcomes (PROs) to assess symptoms in children are not routinely used in clinical practice, yet children with complex conditions experience a significant number of symptoms.AimTo adapt and evaluate the Symptom Screening in Pediatrics Tool (SSPedi), a PRO measure developed in Canada for use with Australian children.MethodsSSPedi wording was adapted and item relevance assessed by an expert clinical group (N = 7) resulting in the Australian version (SSPedi-Aus). Cognitive interviewing with children with cancer (N = 10, 8–18 years) established understanding and difficulty with completing. A second group of child-parent dyads (N = 30) were recruited to evaluate psychometric properties (content validity, test-retest reliability, and parent-proxy) measured with Intraclass Correlation Coefficients (ICC) with 95% Confidence Intervals (CI). Acceptability and usefulness of SSPedi-Aus were also assessed.FindingsConstruct validity was confirmed across all items by 30 children. Child test-retest achieved excellent concordance (ICC 0.98, 95% CI 0.91 to 0.99). Symptoms causing the most distress as reported by children were different to those identified by parents. Although children and parents returned a similar mean total score (13.43 vs. 13.80), there was weak overall interrater reliability (ICC 0.37, 95% CI ?0.26 to 0.70, p = 0.12).ConclusionChildren are distressed by symptoms that may not be identified by parents or reported to clinicians, yet these symptoms are amendable to intervention. The SSPedi-Aus is useful to assess the level of distress caused by symptoms in children.     

Solid lipid microparticles containing loratadine prepared using a Micromixer

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol® ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.     

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis

ABSTRACT: BACKGROUND: The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). METHODS: A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. RESULTS: The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. CONCLUSIONS: A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.     

Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

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Effects of Cling Film Draping Material on Body Temperature of Mice During Surgery

General anesthesia induces many systemic effects, including thermoregulatory impairment and subsequent perioperative hypothermia. Due to the animals’ small size, monitoring and maintaining body temperatures in laboratory rodents during anesthesia is important for successful surgical outcomes and prompt anesthetic recovery. Draping materials have the potential to aid in thermal support during surgical anesthesia. In this study, rectal and surface (infrared) temperatures were measured in C57BL/6 mice under isoflurane anesthesia every 5 min for the duration of a 35-min sham surgery. In addition to placement on a circulating water bath, mice (n = 6/group) were draped with commercial cling film (CF; Press''n Seal, Glad, Oakland, CA), a conventional paper drape (PD), or no drape (ND) during surgery. Results demonstrated that CF-draped animals had significantly higher rectal temperatures than nondraped animals. Furthermore, surface temperatures of CF-draped mice were considerably higher than those of both paper-draped and undraped animals. The data indicate that cling film is an effective material to help minimize hypothermia in mice and potentially in other laboratory rodents requiring general anesthesia.

Surgery and anesthesia introduce many challenges, especially in veterinary medicine, due to the diversity of species. One major challenge during general anesthesia involves changes in an animal''s thermoregulatory ability.^1,14 Body temperatures in mice and rats fall significantly during anesthesia if no thermal support is provided.^29,30 Hypothermia occurs due to drug-induced alterations to the thermoregulatory center, inadequate circulation, and a loss of body heat to the environment from evaporation, radiation, conduction, and convection.⁷ Mice are particularly susceptible to hypothermia, due to their large surface area per gram of body weight, which permits significant physiologic changes in response to fluctuations in the ambient temperature.³¹ Covering the animal''s body with towels, drapes, or blankets to reduce the area exposed to the environment can minimize heat loss.^6,7,13 Placing the animal on an insulated surface can limit conductive heat loss. In larger animals, warmed fluids can be given perioperatively, heated anesthetic gasses can be administered, and heated blankets and heat packs can be applied to body surfaces to provide exogenous heat.^1,7 Safer and more practical methods for rodents are circulating water heating blankets, thermal gel packs, and warming lamps, which are commonly used for thermal support during anesthesia.^5,14 Addressing all of these factors can contribute to maintaining normothermia during anesthesia.Risk of mortality is elevated during anesthesia and in the postoperative period, including in rodents.^1,13 Hypothermia induced by anesthesia can negatively affect rodents by altering vital parameters such as heart rate and blood pressure and delaying anesthetic recovery.^3,5,12,19 These risks require careful selection of an appropriate anesthetic protocol and careful monitoring of the patient throughout anesthesia until full recovery occurs. Strict anesthetic monitoring and the use of supplemental heat devices have been shown to reduce the likelihood of complications, improve overall postoperative recovery, and reduce mortality associated with surgical procedures.^1,7,15,16 However, due to these species’ small size, monitoring equipment must be specialized and is often costly. Cost-effective and practical alternative equipment and materials would facilitate monitoring and care of rodents.Various draping options are available for rodent surgery, and their use is vital for both sterile technique and heat retention. Traditionally, paper draping material has been a popular option, because it is relatively inexpensive and can be autoclaved together with surgical instruments.^15,16 Some institutions have adopted varying methods and types of draping, including no drape and paper draping. Commercial cling film (CF) has been used as draping due to its low cost, ease of use, and sterility straight out of the box.⁹ Our study team sought to evaluate the effects of draping material on intraoperative thermoregulation in mice by measuring rectal temperature (modified rectal probe) and surface temperature (infrared device) during a 35-min laparotomy procedure, with both temperature devices chosen for affordability and availability. We hypothesized that mice draped with CF would maintain a higher intraoperative body temperature under general anesthesia than would mice with traditional paper drapes or no drape.     

Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.

Anesthesia is frequently required for mice used in biomedical research, but anecdotal communications suggest that mice receive significantly less anesthetic monitoring and supportive care than do other research species. Monitoring of anesthetized mice is often minimal due to lack of specialized monitoring equipment, and the fact that many rodent surgeries are performed by a single person who acts as both surgeon and anesthetist. Supportive care during anesthesia is limited by a lack of supporting experimental evidence. The lack of monitoring and supportive care may increase the mortality rate in anesthetized mice.Previous studies have shown that mice anesthetized with both inhalant and injectable anesthetics without supplemental oxygen become profoundly hypoxic.^{1,6,8,9,19,26,39,41} While mice in these studies appear to recover normally from anesthesia, little is known about the effects of hypoxia on physiologic parameters, anesthetic depth, and perioperative mortality. Respiratory complications, including hypoxia and hypoventilation, are second only to cardiovascular complications as a cause of perioperative mortality in veterinary species, and in humans, hypoxemia accounts for over 50% of deaths under anesthesia.⁴ To mitigate the risk of hypoxia under anesthesia, oxygen supplementation is commonly provided to anesthetized humans and animals, but is rarely provided to mice in research settings.^6,19All anesthetics affect respiratory function; ketamine and isoflurane are particularly known to cause respiratory depression in mice and rats by impairing the normal physiologic responses to hypoxemia and hypercapnia.^{9,12,20,23,28} The peripheral chemoreceptors, primarily in the carotid body, normally sense dropping arterial partial pressure of oxygen (PaO₂) while central chemoreceptors located in the medulla sense changes in pH and rising partial pressure of carbon dioxide (PaCO₂).^22,23,29,40 Both sets of chemoreceptors compensate by initiating increases in respiratory rate and tidal volume.^{23,28,31,34,40} Injectable and inhalant anesthetic agents depress the function of these chemoreceptors, preventing the increases in respiration that compensate for hypoxia and hypoventilation.^22,29Pulse oximetry is commonly used to monitor peripheral oxygen saturation and detect the presence of hypoxia. Pulse oximeters use the difference in light absorption of oxygenated hemoglobin and deoxygenated hemoglobin in arterial blood to provide an estimate of arterial oxygen content, abbreviated as SpO₂.¹⁷ An SpO₂ of less than 90% to 95% generally corresponds to a PaO₂ of less than 60 to 80 mm Hg, which is considered hypoxic in most species of mammals.^7,17 Because of the small size of mice, species-specific pulse oximetry equipment is necessary to obtain this measurement. Therefore, measurement of SpO₂ in anesthetized mice is not routinely performed, meaning that hypoxia under anesthesia generally goes unrecognized, and is likely more common than is appreciated by our field.The purpose of this study was to confirm that mice become hypoxic after receiving a ketamine/xylazine based anesthetic admixture or isoflurane, which are commonly used anesthetics in mice and to investigate the effects of oxygen supplementation on anesthetic depth, physiologic values, and anesthetic requirements in these mice.^9,35 We hypothesized that mice not receiving supplemental oxygen would be hypoxic, as indicated by lower SpO₂ while anesthetized, and that supplemental oxygen would correct this hypoxia. We also hypothesized that oxygen supplementation would increase the doses of injectable and inhalant anesthesia necessary to maintain mice at a surgical plane of anesthesia.