The prevention of childhood anxiety and promotion of resilience among preschool-aged children : a universal school based trial

This study is the first to examine the effectiveness of the Fun FRIENDS programme, a school-based, universal preventive intervention for early childhood anxiety and promotion of resilience delivered by classroom teachers. Participants (N = 488) included children aged 4–7 years attending 1 of 14 Catholic Education schools in Brisbane, Australia. The schools were randomly allocated to one of three groups, the intervention, active comparison and waitlist control group. Parents completed standardized measures of anxiety and behavioural inhibition (BI), resilience, social and emotional functioning and behaviour difficulties in addition to parental stress and anxiety, at pre- and post- and 12-month follow-up. Teachers also completed a parallel measure of social and emotional strength at the three time points. Comparable results were obtained for the intervention and comparison groups; however, the intervention group (IG) achieved greater reductions in BI, child behavioural difficulties and improvements in social and emotional competence. In addition, significant improvements in parenting distress and parent–child interactions were found for the IG, with gains maintained at 12-month follow-up. Teacher reports revealed more significant improvement in social and emotional competence for the IG. Clinical implications of the findings are discussed, along with limitations and directions for future research.

Crushed tablets : does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas : an exception to the norm

Cancer that arises from the ovarian surface epithelium (OSE) accounts for approximately 90% of human ovarian cancer, and is the fourth leading cause of cancer-related deaths among women in developed countries. The pathophysiology of epithelial ovarian cancer is still unclear because of the poor understanding of the complex nature of its development and the unusual mechanism(s) of disease progression. Recent studies have reported epithelial-mesenchymal transition (EMT) in cultured OSE and ovarian cancer cell lines in response to various stimuli, but our understanding of the importance of these observations for normal ovarian physiology and cancer progression is not well established. This review highlights the current literature on EMT-associated events in normal OSE and ovarian cancer cell lines, and discusses its implication for normal ovarian function as well as acquisition of neoplastic phenotypes. The pathological changes in OSE in response to EMT during neoplastic transformation and the contribution of hormones, growth factors, and cytokines that initiate and drive EMT to sustain normal ovarian function, as well as cancer development and progression are also discussed. Finally, emphasis is placed on the clinical implications of EMT and potential therapeutic opportunities that may arise from these observations have been proposed.

Validation of accelerometry for physical activity measurement in ambulant adolescents with cerebral palsy

Background Promoting participation physical activity (PA) is an important means of promoting healthy growth and development in children with cerebral palsy (CP). The ActiGraph is a uniaxial accelerometer that provides a realtime measure of PA intensity, duration and frequency. Its small, light weight design makes it a promising measure of activity in children with CP. To date no study has validated the use of accelerometry as a measure of PA in ambulant adolescents with CP. Objectives To evaluate the validity of the ActiGraph accelerometer for measuring PA intensity in adolescents with CP, using oxygen consumption (VO2), measured using portable indirect calorimetry (Cosmed K4b2), as the criterion measure. Design Validation Study Participants/Setting: Ambulant adolescents with CP aged 10–16 years, GMFCS rating of I-III. The recruitment target is 30 (10 in each GMFCS level). Materials/Methods Participants wore the ActiGraph (counts/min) and a Cosmed K4b2 indirect calorimeter (mL/kg/min) during six activity trials: quiet sitting (QS), comfortable paced walking (CPW), brisk paced walking (BPW), fast paced walking (FPW), a ball-kicking protocol (KP) and a ball-throwing protocol (TP). MET levels (multiples of resting metabolism) for each activity were predicted from ActiGraph counts using the Freedson age-specific equation (Freedson et al. 2005) and compared with actual MET levels measured by the Cosmed. Predicted and measured METs for each activity trial were classified as light (> 1.5 METs and <4.6 METs) or moderate to vigorous intensity (≥ 4.6 METs). Results To date 36 bouts of activity have been completed (6 participants x 6 activities). Mean VO2 increased linearly as the intensity of the walking activity increased (CPW=9.47±2.16, BPW=14.06±4.38, FPW=19.21±5.68 ml/kg/min) and ActiGraph counts reflected this pattern (CPW=1099±574, BPW=2233±797 FPW=4707±1013 counts/min). The throwing protocol recording the lowest VO2 (TP=7.50±3.86 ml/kg/min) and lowest overall counts/min (TP=31±27 counts/min). When each of the 36 bouts were classified as either light or moderate to vigorous intensity using measured VO2 as the criterion measure, the Freedson equation correctly classified 28 from 36 bouts (78%). Conclusion/Clinical Implications These preliminary findings suggest that there is a relationship between the intensity of PA and direct measure of oxygen consumption and that therefore the ActiGraph may be a promising tool for accurately measuring free living PA in the community. Further data collection of the complete sample will enable secondary analysis of the relationship between PA and severity of CP (GMFCS level).

Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer

Castration is the standard therapy for advanced prostate cancer (PC). Although this treatment is initially effective, tumors invariably relapse as incurable, castration-resistant PC (CRPC). Adaptation of androgen-dependent PC cells to an androgen-depleted environment or selection of pre-existing,CRPC cells have been proposed as mechanisms of CRPC development. Stem cell (SC)-like PC cells have been implicated not only as tumor initiating/maintaining in PC but also as tumor-reinitiating cells in CRPC. Recently, castration-resistant cells expressing the NK3 homeobox 1 (Nkx3-1) (CARNs), the other luminal markers cytokeratin 18 (CK18) and androgen receptor (AR), and possessing SC properties, have been found in castrated mouse prostate and proposed as the cell-of-origin of CRPC. However, the human counterpart of CARNs has not been identified yet. Here, we demonstrate that in the human PC xenograft BM18, preexisting SC-like and neuroendocrine (NE) PC cells are selected by castration and survive as totally quiescent. SClike BM18 cells, displaying the SC markers aldehyde dehydrogenase 1A1 or NANOG, coexpress the luminal markers NKX3-1, CK18, and a low level of AR (ARlow) but not basal or NE markers. These CR luminal SC-like cells, but not NE cells, reinitiate BM18 tumor growth after androgen replacement. The ARlow seems to mediate directly both castration survival and tumor reinitiation. This study identifies for the first time in human PC SC-/CARN-like cells that may represent the cell-of-origin of tumor reinitiation as CRPC. This finding will be fundamental for refining the hierarchy among human PC cancer cells and may have important clinical implications.

Delivering crushed paracetamol tablets using thickened fluids : does it alter the pharmacokinetics?

Dysphagia, often associated with conditions such as stroke, Parkinson’s disease, multiple sclerosis, and dementia, causes patients to have difficulty with swallowing food and/or liquids. These patients require their fluids to be thickened using gum-based thickening powders in order to facilitate safe swallowing. These thickened fluids are also used as a vehicle for delivery of crushed medicines. Our in vitro measurements suggest that thickened fluids can delay and reduce the dissolution of a number of medications. This study was conducted to assess the impact of the use of thickened fluids on the clinical pharmacokinetics of oral paracetamol. METHODS 20 Healthy volunteers were administered a single oral dose (1g) of paracetamol as either whole tablets, crushed with water, crushed with semi-solid jam, or crushed with thickened fluid according to a randomised, crossover design. Saliva samples were collected periodically over 8 hr and paracetamol concentration analysed by HPLC-UV. Non-compartmental pharmacokinetic analysis was conducted using Winnonlin®. RESULTS The mean peak concentration (Cmax) of paracetamol ranged between 5.62 – 8.00 μg/mL. Comparison between the crushed paracetamol with thickened water (Level 900) and other treatment options (whole, crushed with water, and crushed with jam) showed there was a significant difference in Cmax at 90% CI (p < 0.05). Also, whole tablet had a significant difference in Cmax between crushed with water and crushed with jam. There was no significant difference in AUC irrespective of the treatment. DISCUSSION The use of thickened water resulted in alteration in the absorption kinetics of paracetamol. Given this interaction, co-administration with thickened fluids may have important clinical implications for medications with a narrow therapeutic index.

A method for optimal fit of patient-specific fracture fixation plates

Anatomically pre-contoured fracture fixation plates are a treatment option for bone fractures. A well-fitting plate can be used as a tool for anatomical reduction of the fractured bone. However, recent studies showed that some plates fit poorly for many patients due to considerable shape variations between bones of the same anatomical site. Therefore, the plates have to be manually fitted and deformed by surgeons to fit each patient optimally. The process is time-intensive and labor-intensive, and could lead to adverse clinical implications such as wound infection or plate failure. This paper proposes a new iterative method to simulate the patient-specific deformation of an optimally fitting plate for pre-operative planning purposes. We further demonstrate the validation of the method through a case study. The proposed method involves the integration of four commercially available software tools, Matlab, Rapidform2006, SolidWorks, and ANSYS, each performing specific tasks to obtain a plate shape that fits optimally for an individual tibia and is mechanically safe. A typical challenge when crossing multiple platforms is to ensure correct data transfer. We present an example of the implementation of the proposed method to demonstrate successful data transfer between the four platforms and the feasibility of the method.

The lipophilic opioids: Fentanyl, alfentanil, sufentanil and remifentanil

discusses fentanyl, alfentanil, sufentanil, and remifentanil which are synthetic opioid analgesics with high affinity for the mu opioid receptor. They have been widely adopted in anaesthetic practice for various surgical procedures (e.g. in cardiac surgery) and for long-term analgesia and sedation. Important pharmacokinetic differences between these analgesics have been described, and this chapter addresses how the pharmacokinetic profile of each analgesic is affected by many factors, including patient age, plasma protein content, acid–base balance status, cardiopulmonary bypass, changes in hepatic blood flow, and the co-administration of other drugs which compete for plasma protein carriers and metabolic pathways, although their profile is not significantly affected by renal insufficiency or compensated hepatic dysfunction, which has major clinical implications.

Mothers' perception of the quality of childhood sibling relationships affected by disability

The quality of the sibling relationship has an important role in the development of psychosocial skills throughout childhood. While the literature suggests that the significance of sibling relationships is heightened when one sibling has a disability, empirical findings about the quality of these relationships are few and inconsistent. The present study aimed to address this gap, by investigating mothers’ perspectives about the impact of disability on the quality of the childhood sibling relationship. Forty-one mothers with a child with disability, and 48 with no children with disability completed an online questionnaire that assessed the amount of perceived warmth/closeness and conflict in their children’s sibling relationship. It was found that while there were no differences in reported conflict between the two groups, mothers with a child with disability reported significantly lower warmth/closeness in their children’s sibling relationship than mothers without a child with disability. Demographic variables such as number of children, gender grouping, target gender, target age and age order did not moderate this result. Mothers overall reported significantly more warmth/closeness for younger rather than older children, and more conflict when the sibling was younger than the target child as opposed to older than them. Clinical implications for intervention are discussed.

Comparative in vitro and in vivo studies of enteric-coated pancrelipase preparations for pancreatic insufficiency

We evaluated three acid-resistant pancreatic enzyme preparations by in vitro assays, and by comparing degree of steatorrhea, creatorrhea, fecal wet weight, and stool energy losses in a randomized crossover study of patients with pancreatic insufficient cystic fibrosis. Aims of the study were to assess (a) the most practicable and reliable indicator of malabsorption; (b) the variation in enzyme batch potency; (c) the decline in enzyme batch potency with prolonged shelf life; and (d) the relative bio-efficacy of the different preparations. In the in vivo study, absorption of energy, nitrogen, and fat did not differ when comparing the three preparations at roughly pharmaceu-tically equivalent doses, but when expressed per capsule of pancreatic supplement ingested, absorption reflected relative enzyme content, favoring the higher potency preparations. Although steatorrhea was reasonably controlled by these preparations, stool energy losses varied from 800 to 1,100 kJ per day, suggesting greater attention be paid to overall energy absorption rather than absorption of individual nutrients. In addition, fecal energy loss correlated more closely with fecal wet weight (r = 0.81; p < 0.05) than with steatorrhea (r = 0.40; ns), such that 1 g wet feces = 8.37 kJ (± 0.14). In vitro enzyme potency varied markedly between batches of the same brand, and also a decline of up to 20% in amylase, lipase, and trypsin activity was noted over an 8-month period for each batch. Both observations have clinical implications at times of represcription. Finally, the higher potency preparations were more effective per capsule and reduced capsule dosage is therefore attainable. © 1993 Raven Press, Ltd., New York.

Inpatient experience of anorexia nervosa

Anorexia nervosa (AN) is an extremely serious mental illness, with a high mortality rate and many debilitating physical and psychological symptoms. While hospitalisation is sometimes required for patients with AN there remains no evidence base for “best practice’ inpatient treatment. With patients’ views recognised as critical to improving efficiency and outcomes, calls have been made for more qualitative research into inpatients’ experiences. In light of this the current paper utilised thematic analysis to examine 16 semi-structured interviews with inpatients diagnosed with AN, at a specialised eating disorders hospital unit. The study found an overarching theme of relationship ambivalence in connection with sub-themes of patients’ eating disorders, eating disorder co-patients, staff and treatment. Participants’ goals in relationship to their eating disorder and engagement in treatment shaped and were shaped by interactions with other inpatients with AN and staff. Clinical implications for this study and future research directions are discussed.

Implications of comorbidity for clinical practice

In the past, people with comorbidity have often received inadequate care. The ethical principle of equal access to quality services has important implications for agencies, when combined with knowledge about comorbidity and its management, and about diffusion of innovations across organizations. Comorbidity is common, and often has profound impacts on individuals and families. Tobacco smoking in particular is endemic and affects morbidity, mortality, and functioning. This implies that screening for co-occurring problems should be routine, and that a boutique comorbidity service is impractical. Large numbers mean that universal screening and intervention must be capable of large-scale implementation. Since multiple, closely linked problems are often present, treatments should address these multiple issues, and closely interrelated problems will require well-integrated treatment. Involvement of a single health agency is typically needed. Numbers and severity of problems can blind practitioners and patients to strengths and unaffected areas; these should be assessed and fostered. Better policies and practices for co-occurring disorders will require organizational change. Co-occurring disorders must become core business for organizations and practitioners, so that effective comorbidity practice is rewarded, required skills are present or taught, cues to use the practices are provided, and a culture supporting their application is established.

Pan-Plasmodium band sensitivity for Plasmodium falciparum detection in combination malaria rapid diagnostic tests and implications for clinical management

Background: Malaria rapid diagnostic tests (RDTs) are appropriate for case management, but persistent antigenaemia is a concern for HRP2-detecting RDTs in endemic areas. It has been suggested that pan-pLDH test bands on combination RDTs could be used to distinguish persistent antigenaemia from active Plasmodium falciparum infection, however this assumes all active infections produce positive results on both bands of RDTs, an assertion that has not been demonstrated. Methods: In this study, data generated during the WHO-FIND product testing programme for malaria RDTs was reviewed to investigate the reactivity of individual test bands against P. falciparum in 18 combination RDTs. Each product was tested against multiple wild-type P. falciparum only samples. Antigen levels were measured by quantitative ELISA for HRP2, pLDH and aldolase. Results: When tested against P. falciparum samples at 200 parasites/μL, 92% of RDTs were positive; 57% of these on both the P. falciparum and pan bands, while 43% were positive on the P. falciparum band only. There was a relationship between antigen concentration and band positivity; ≥4 ng/mL of HRP2 produced positive results in more than 95% of P. falciparum bands, while ≥45 ng/mL of pLDH was required for at least 90% of pan bands to be positive. Conclusions: In active P. falciparum infections it is common for combination RDTs to return a positive HRP2 band combined with a negative pan-pLDH band, and when both bands are positive, often the pan band is faint. Thus active infections could be missed if the presence of a HRP2 band in the absence of a pan band is interpreted as being caused solely by persistent antigenaemia.