Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol

Background

There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum.

Methods/Design

The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged ≤ 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs.

Discussion

The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice.

Trial Registration

Current Controlled Trials ISRCTN61735247     

Characterization of mycobacterial virulence genes through genetic interaction mapping

We have previously shown that approximately 5% of the genes encoded by the genome of Mycobacterium tuberculosis are specifically required for the growth or survival of this bacterium during infection. This corresponds to hundreds of genes, most of which have no identifiable function. As a unique approach to characterize these genes, we developed a method to rapidly delineate functional pathways by identifying mutations that modify each other's phenotype, i.e., "genetic interactions". Using this method, we have defined a complex set of interactions between virulence genes in this pathogen, and find that the products of unlinked genes associate to form multisubunit transporters that are required for bacterial survival in the host. These findings implicate a previously undescribed family of transport systems in the pathogenesis of tuberculosis, and identify genes that are likely to function in the metabolism of their substrates. This method can be readily applied to other organisms at either the single pathway level, as described here, or at the system level to define quantitative genetic interaction networks.     

A simple and sensitive high-performance liquid chromatographic method for the determination of vinflunine and 4-O-deacetylvinflunine from human blood

Vinflunine (VFL) is the first bifluorinated tubulin-targeted agent obtained through a semi synthetic process using superacidic chemistry. Pharmacologic models evidenced a high degree of activity from several cancer lines. The intravenous formulation of VFL (Javlor, Pierre Fabre Medicament, Boulogne, France) is registered for bladder cancer and is undergoing Phase III trials for nonsmall cell lung and breast cancer. To support most of the pharmacokinetic studies in humans, a sensitive high-performance liquid chromatography bioanalytical method coupled with ultraviolet detection was developed and validated for the simultaneous quantification of VFL and its active metabolite 4-O-deacetylvinflunine. The two compounds, together with 17-bromovinorelbine, used as an internal standard, were extracted from blood (1 mL) by a liquid-liquid process under basic conditions using diethyl ether. The organic phase was then back-extracted with HCl 0.1 mol/L. Analysis was performed through a cyano column and detection was set at 268 nm. Total analysis run time was less than 15 minutes. The assay was sensitive for the two compounds to at least 2 ng/mL and calibration curves were linear up to 200 ng/mL. The between-run imprecision and the mean inaccuracy were lower than 7% and 8.3%, respectively. Blood samples were stable when stored at -70°C over 24 months. The long-term reproducibility and the suitability of this analytical method were demonstrated through the analysis of about 6000 biologic samples during the clinical development of intravenous VFL. This method is adequately sensitive to monitor the blood concentrations observed at the recommended dose defined in a clinical setting.     

A comparison of propofol and amobarbital for use in the Wada test

129 Wada procedures were reviewed to examine the suitability of propofol (n=54) as a replacement to amobarbital (n=75) for use as an anaesthetic in the Wada test. Suitability was considered with respect to length of hemiplegia induced, the frequency of side effects and patient memory scores. Data was retrospectively collected from records of patients who had undergone the Wada procedure between 2004 and 2009 in Beaumont Hospital, Dublin. No significant differences were found between the two drugs on any of the measures. The results suggest that propofol represents a suitable alternative to amobarbital for use in the Wada procedure.     

Association of the joint effect of menopause and hormone replacement therapy and cancer in African American women: the Jackson Heart Study

Cancer is the second leading cause of death in the US and in Mississippi. Breast cancer (BC) is the most common cancer among women, and the underlying pathophysiology remains unknown, especially among African American (AA) women. The study purpose was to examine the joint effect of menopause status (MS) and hormone replacement therapy (HRT) on the association with cancers, particularly BC using data from the Jackson Heart Study. The analytic sample consisted of 3202 women between 35 and 84 years of which 73.7% and 22.6% were postmenopausal and on HRT, respectively. There were a total of 190 prevalent cancer cases (5.9%) in the sample with 22.6% breast cancer cases. Menopause (p<0.0001), but not HRT (p=0.6402), was independently associated with cancer. Similar results were obtained for BC. BC, cancer, hypertension, type 2 diabetes, prevalent cardiovascular disease, physical activity and certain dietary practices were all significantly associated with the joint effect of menopause and HRT in the unadjusted analyses. The family history of cancer was the only covariate that was significantly associated with cancer in the age-adjusted models. In examining the association of cancer and the joint effect of menopause and HRT, AA women who were menopausal and were not on HRT had a 1.97 (95% CI: 1.15, 3.38) times odds of having cancer compared to pre-menopausal women after adjusting for age; which was attenuated after further adjusting for family history of cancer. Given that the cancer and BC cases were small and key significant associations were attenuated after adjusting for the above mentioned covariates, these findings warrant further investigation in studies with larger sample sizes of cancer (and BC) cases.     

Defining sensory modulation: A review of the concept and a contemporary definition for application by occupational therapists

Background: Sensory interventions are prevalent amongst adult mental health practitioners and are supported by major stakeholders and policy makers across the world. The term commonly used by occupational therapists applying sensory practices is sensory modulation, however this term has evolved.

Aims: This paper aims to investigate and clarify the definition of ‘sensory modulation’ for application by occupational therapists.

Method: A framework guided this concept analysis on sensory modulation. A summative content analysis approach was employed to code results.

Results: Six conceptual themes for sensory modulation were identified. 81% of authors defined sensory modulation as consisting of more than one of these themes. 18% of authors defined sensory modulation as both a neurophysiological process and means to regulate behaviour.

Conclusion: The concept of sensory modulation has evolved in occupational therapy practice. The authors summarise with the following proposed definition of sensory modulation for contemporary occupational therapy practice: ‘Sensory modulation is considered a twofold process. It originates in the central nervous system as the neurological ability to regulate and process sensory stimuli; this subsequently offers the individual an opportunity to respond behaviourally to the stimulus’.

Significance: A contemporary definition of ‘sensory modulation’ has been identified for occupational therapy practice.     

Remote telephone clinics in oral medicine: reflections on the place of virtual clinics in a specialty that relies so heavily on visual assessment. A note of caution

During the COVID-19 pandemic, NHS services had to convert face-to-face consultations to remote consultations to facilitate the ongoing provision of healthcare. Many specialties including Oral and Maxillofacial Surgery and Rheumatology have found such virtual clinics effective and appreciated by both patients and clinicians. In Oral Medicine, whilst responses to virtual clinics have been positive, we have recognised that they are not sufficient. In this reflective piece, we describe our experiences and our approach to their use in the management of Oral Medicine and Behçet’s disease patients, which has developed iteratively during the lockdown period. We also consider the role of virtual clinics in Oral Medicine in the post-COVID-19 era.     

Small atypical leiomyomas: report of two cases

We describe two small atypical leiomyomas. The first was a 6-mm de novo lesion in a 53-year-old woman. The second was a 3-mm focus in a 12-mm leiomyoma in a 45-year-old woman. Both lesions showed moderate atypia and a mitotic rate of six per 10 high-power fields. Coagulative necrosis was not seen. Neither patient had received exogenous oestrogen or progestogen. There was no evidence of recurrence or metastasis in either patient after 60 months of follow-up. Our report provides evidence that atypical uterine leiomyomas may arise either de novo or within a leiomyoma.     

Clinical Review: Familial Mediterranean Fever—An Overview of Pathogenesis,Symptoms, Ocular Manifestations,and Treatment

Familial Mediterranean fever is an autoinflammatory multisystem disease, which most commonly affects patients from the Mediterranean basin. This review discusses the common polymorphisms in the MEFV gene as well as the role of pyrin in disease pathogenesis. Patients with familial Mediterranean fever typically develop peritonitis, pleuritis, arthritis, and fever. In addition, a number of authors have reported ophthalmic features. These case reports and series are further explored in this review. Colchicine has transformed the prognosis for patients with familial Mediterranean fever. The rationale for the use of colchicine, as well as the evidence for newer biologic agents is also covered.