Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA-protein interaction.

PURPOSE: Most classical aniridia is caused by PAX6 haploinsufficiency. PAX6 missense variants can be hypomorphic or mimic haploinsufficiency. We hypothesized that missense variants also cause previously undescribed disease by altering the affinity and/or specificity of PAX6 genomic interactions. METHODS: We screened PAX6 in 372 individuals with bilateral microphthalmia, anophthalmia, or coloboma (MAC) from the Medical Research Council Human Genetics Unit eye malformation cohort (HGUeye) and reviewed data from the Deciphering Developmental Disorders study. We performed cluster analysis on PAX6-associated ocular phenotypes by variant type and molecular modeling of the structural impact of 86 different PAX6 causative missense variants. RESULTS: Eight different PAX6 missense variants were identified in 17 individuals (15 families) with MAC, accounting for 4% (15/372) of our cohort. Seven altered the paired domain (p.[Arg26Gln]x1, p.[Gly36Val]x1, p.[Arg38Trp]x2, p.[Arg38Gln]x1, p.[Gly51Arg]x2, p.[Ser54Arg]x2, p.[Asn124Lys]x5) and one the homeodomain (p.[Asn260Tyr]x1). p.Ser54Arg and p.Asn124Lys were exclusively associated with severe bilateral microphthalmia. MAC-associated variants were predicted to alter but not ablate DNA interaction, consistent with the electrophoretic mobility shifts observed using mutant paired domains with well-characterized PAX6-binding sites. We found no strong evidence for novel PAX6-associated extraocular disease. CONCLUSION: Altering the affinity and specificity of PAX6-binding genome-wide provides a plausible mechanism for the worse-than-null effects of MAC-associated missense variants.

Dietitians' practice in giving carbohydrate advice in the management of type 2 diabetes: a mixed methods study.

BACKGROUND: Carbohydrate is accepted as the principal nutrient affecting blood glucose in diabetes; however, current guidelines are unable to specify the optimal quantity of carbohydrate for glycaemic control. No studies exist that describe current practice amongst healthcare professionals giving carbohydrate advice in type 2 diabetes. The present study aims to improve understanding of the degree of variation in the current practice of UK registered dietitians (RDs) by describing how RDs advise patients. METHODS: UK RDs were contacted through national networks and asked to complete an online survey, which was analysed using stata, version 12 (StataCorp, College Station, TX, USA). Three consultations between dietitians and patients with type 2 diabetes were observed, followed by semi-structured interviews with the dietitians. RESULTS: In total, 320 complete survey responses were received. Dietitians' advice varied according to expertise, training and confidence, and the complexity of the patient's blood glucose treatment. Some 48% (n = 154) of respondents advised patients to restrict carbohydrate intake either occasionally or frequently, with 35.6% (n = 114) considering 30-39% of total energy from carbohydrate to be a realistic expectation. The overall theme from the interviews was 'Conflicting Priorities', with three sub-themes: (i) how treatment decisions are made; (ii) the difference between empowerment and advice; and (iii) contradictory advice. A disparity existed between what was observed and interview data on how dietitians rationalise the type of carbohydrate advice provided. CONCLUSIONS: Dietitians' advice varies for a number of reasons. Consensus exists in some areas (e.g. carbohydrate awareness advice); however, clear definitions of such terms are lacking. Clarification of interventions may improve the consistency of approach and improve patient outcomes.

Simulation of dielectrophoretic assembly of carbon nanotubes using 3D finite element analysis.

One of the most important methods for selective and repeatable assembly of carbon nanotubes (CNTs) is alternating current dielectrophoresis (DEP). This method has been demonstrated experimentally as a viable technique for nano-scale manufacturing of novel CNT based devices. Previous numerical analyses have studied the motion of nanotubes, the volume from which they are assembled, and the rate of assembly, but have been restricted by various simplifying assumptions. In this paper we present a method for simulating the motion and behavior of CNTs subjected to dielectrophoresis using a three-dimensional electrostatic finite element analysis. By including the CNT in the finite element model, we can accurately predict the effect of the CNT on the electric field and the resulting force distribution across the CNT can be determined. We have used this information to calculate the motion of CNTs assembling onto the electrodes, and show how they tend to move towards the center of an electrode and come into contact at highly skewed angles. Our analysis suggests that the CNTs move to the electrode gap only after initially contacting the electrodes. We have also developed a model of the elastic deformation of CNTs as they approach the electrodes demonstrating how the induced forces can significantly alter the CNT shape during assembly. These results show that the CNT does not behave as a rigid body when in close proximity to the electrodes. In the future this method can be applied to a variety of real electrode geometries on a case-by-case basis and will provide more detailed insight into the specific motion and assembly parameters necessary for effective DEP assembly.

Gingival crevicular fluid proteomes in health, gingivitis and chronic periodontitis.

OBJECTIVE: The aim of this study was to compare the proteome composition of gingival crevicular fluid obtained from healthy periodontium, gingivitis and chronic periodontitis affected sites. BACKGROUND: Owing to its site-specific nature, gingival crevicular fluid is ideal for studying biological processes that occur during periodontal health and disease progression. However, few studies have been conducted into the gingival crevicular fluid proteome due to the small volumes obtained. METHODS: Fifteen males were chosen for each of three different groups, healthy periodontium, gingivitis and chronic periodontitis. They were categorized based on clinical measurements including probing depth, bleeding on probing, plaque index, radiographic bone level, modified gingival index and smoking status. Gingival crevicular fluid was collected from each patient, pooled into healthy, gingivitis and chronic periodontitis groups and their proteome analyzed by gel electrophoresis and liquid chromatography electrospray ionization ion trap tandem mass spectrometry. RESULTS: One hundred and twenty-one proteins in total were identified, and two-thirds of these were identified in all three conditions. Forty-two proteins were considered to have changed in abundance. Of note, cystatin B and cystatin S decreased in abundance from health to gingivitis and further in chronic periodontitis. Complement proteins demonstrated an increase from health to gingivitis followed by a decrease in chronic periodontitis. Immunoglobulins, keratin proteins, fibronectin, lactotransferrin precursor, 14-3-3 protein zeta/delta, neutrophil defensin 3 and alpha-actinin exhibited fluctuations in levels. CONCLUSION: The gingival crevicular fluid proteome in each clinical condition was different and its analysis may assist us in understanding periodontal pathogenesis.

An in vitro comparison of detection methods for approximal carious lesions in primary molars.

BACKGROUND/AIMS: This study aimed to compare and contrast in vitro six methods to determine the most accurate method for detecting approximal carious lesions in primary molars. METHODS: Extracted primary molars (n = 140) were stored in 0.02% chlorhexidine solution and mounted in light-cured resin in pairs. The six carious lesion detection methods used by the three examiners to assess approximal carious lesions were visual inspection, digital radiography, two transillumination lights (SDI and NSK), and two laser fluorescence instruments (CDD and DDP). Five damaged teeth were discarded. The teeth (n = 135) were sectioned, serially ground, and examined under light microscopy using Downer's histological (HST) criteria as the gold standard. Intra- and inter-examiner reliability, agreement with HST, specificity, sensitivity, receiver operating characteristic (ROC) curves, and areas under the curve were calculated. RESULTS: This study found visual inspection to be the most accurate method when validated by histology. Transillumination with NSK light had the highest specificity, and digital radiography had the highest sensitivity for detecting enamel and/or dentinal carious lesions. Combining specificity and sensitivity into the area under ROC curves, enamel plus dentinal lesions were detected most accurately by visual inspection followed by digital radiography; dentinal lesions were detected most accurately by digital radiography followed by visual inspection. CONCLUSIONS: None of the four newly developed methods can be recommended as suitable replacements for visual inspection and digital radiography in detecting carious lesions on approximal surfaces of primary molars, and further developmental work is needed.

Remineralisation by chewing sugar-free gums in a randomised, controlled in situ trial including dietary intake and gauze to promote plaque formation.

Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not.

Periosteal muscle anchoring for large angle incomitant squint.

PURPOSE: To describe a surgical technique for correcting very large angle exodeviations and determine long term outcomes leading to the evolution of surgical technique. METHODS: A consecutive series of seven patients with large angle, incomitant squint were operated on at Moorfields Eye Hospital over a five-year period using periosteal anchoring by a joint Strabismus/Adnexal team. All patients underwent anchoring of the insertion of the medial rectus (MR) muscle to the periosteum of the medial orbital wall via a retrocaruncular approach, with or without lateral rectus (LR) disinsertion and suturing to the lateral orbital rim connective tissue. Retrospective analysis of notes assessed previous procedures, prism dioptre (PD) deviations and complications. RESULTS: Included were seven eyes (five right, two left) of seven patients (two female, five male). Median age at first anchoring procedure was 25 years (range 4-57). Mean follow up was 34 months (range 8-66). Six patients had long-standing third nerve palsy, one patient had Moebius syndrome. Pre-operative exotropia ranged from 45 to 115 PDs (mean 76, median 75). At the final follow up, all patients had reduced horizontal deviations ranging from 0 to 80 PDs (mean 34, median 30). Further surgery was required in three patients all of whom did not undergo release of the LR muscle at the first procedure. CONCLUSION: Large angle incomitant divergent squints present a particularly difficult surgical challenge. We advocate a combined bi-rectus fixation approach to hold the globe in the primary position.

Microbiome profiles of non-responding and responding paired periodontitis sites within the same participants following non-surgical treatment.

Aim: Periodontitis is a site-specific, chronic disease treated by non-surgical debridement of subgingival plaque. We aimed to determine the microbiome of sites that did not respond to this treatment (NR) compared with paired good responding (GR) sites before and after treatment. Materials and methods: In a longitudinal cohort study, clinical parameters of disease and biological samples were taken prior to and 3 months after treatment. Twelve NR sites from six participants were paired with GR sites within the same participant. Subgingival plaque samples were subjected to bacterial community analysis using 16S rRNA gene sequencing. Results: There were no significant differences in clinical parameters and microbial communities at baseline between GR and NR sites. Bacterial communities in deep pockets were dominated by a small number of species, notably Porphyromonas gingivalis and Treponema denticola. In NR sites three months after treatment there was no significant change in bacterial composition whilst there was a collapse in the abundance of pathobionts in GR sites. Conclusion: NR sites were not identifiable prior to treatment by clinical or microbiological parameters. Treatment failed to disrupt pathogenic bacterial community in NR sites. Targeted suppression of particular species should be considered to initiate community collapse and aid disease resolution.

Casein phosphopeptide-amorphous calcium phosphate incorporated into sugar confections inhibits the progression of enamel subsurface lesions in situ.

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has been demonstrated to exhibit anticariogenic activity in randomized, controlled clinical trials of sugar-free gum and a tooth cream. Two randomized, double-blind, crossover studies were conducted to investigate the potential of CPP-ACP added to hard candy confections to slow the progression of enamel subsurface lesions in an in situ model. The confections studied were: (1) control sugar (65% sucrose + 33% glucose syrup); (2) control sugar-free; (3) sugar + 0.5% (w/w) CPP-ACP; (4) sugar + 1.0% (w/w) CPP-ACP; (5) sugar-free + 0.5% (w/w) CPP-ACP. Participants (10 and 14 in study 1 and 2) wore a removable palatal appliance containing enamel half-slabs with subsurface lesions, except for meals and oral hygiene procedures, and consumed 1 confection 6 times a day for 10 days. The enamel half-slabs were inset to allow the development of plaque on the enamel surface. Participants rested for 1 week before crossing over to another confection. The appliances were stored in a humid container at 37 degrees C when not in the mouth. After each treatment period, the enamel half-slabs were removed, paired with their demineralized control half-slabs, embedded, sectioned and then analysed using transverse microradiography. In both studies consumption of the control sugar confection resulted in significant demineralization (progression) of the enamel subsurface lesions. However, consumption of the sugar confections containing CPP-ACP did not result in lesion progression, but in fact in significant remineralization (regression) of the lesions. Remineralization by consumption of the sugar + 1.0% CPP-ACP confection was significantly greater than that obtained with the sugar-free confection.

Evolving trends in strabismus following retinal surgery: is there still a role for botulinum toxin?

Purpose Ocular motility disturbances following retinal detachment surgery are well documented, resulting in ocular misalignment and disabling diplopia. Interestingly, there has been a downward trend over the last decade across the United Kingdom with the evolution of refined vitrectomy techniques and instrumentation. We aim to report our updated experience on factors influencing botulinum toxin outcomes in view of the trend toward vitrectomy. Methods The Moorfields strabismus service carried out a follow-up retrospective study of all subjects that received botulinum toxin for retinal surgery-related strabismus at our center over an eleven-year period. All new onset constant or intermittent strabismus following retinal detachment surgery were included. Botulinum toxin response was stratified to good and poor. Results 32 patients fulfilled our criteria, with a mean follow-up of 20 months. The majority were vitrectomised eyes (62%), presented with diplopia (60%) and exotropia (66%). All isolated and combined vertical deviations (18%) were noted among cryobuckled eyes only. Baseline largest mean horizontal deviation was 49 and 51 prism diopters (PD) among the good and poor responders, respectively. A statistically and clinically significant reduction in the horizontal angle of deviation was noted among the good (p < .0001) responders, requiring a mean of six injections, in comparison to the poor responders (p = .03). Of the good responders, five patients (16%) with decompensated phorias regained fusion control. A small number of complications (15%) were noted, the most marked being intractable diplopia in a good responder (3%) with failure to fuse. Conclusions Botulinum toxin is a useful treatment modality, particularly when surgical options are limited. It can restore binocularity in patients with preexisting fusion potential. Ocular cosmesis can be achieved but requires ongoing injections. Barriers to fusion restoration include multiple retinal surgeries, persistent macula pathology and central-peripheral retinal rivalry. This highlights the need for rigorous baseline macula assessment to allow a tailored approach when considering botulinum toxin therapy for strabismus.

Paediatric endophthalmitis: a UK retrospective study.

INTRODUCTION: Paediatric endophthalmitis is a severe but rare complication of intraocular surgery, penetrating trauma and far less commonly extra-ocular surgery or endogenous origin. We set out to establish the incidence and risk factors of exogenous endophthalmitis in children, and to develop an evidence-based protocol that can be used for treatment of suspected exogenous endophthalmitis in children. METHODS: Microbiology reports and operation numbers were obtained from two large tertiary referral hospitals sharing 24-h paediatric ophthalmology cover for the period January 2009-December 2016. All cases of aqueous and/or vitreous tap performed on children aged ≤18 years were identified and case notes reviewed for complete information on each case. RESULTS: Sixteen cases were eligible for inclusion as 'postoperative endophthalmitis': complete data was found on 13 cases. The incidence of postoperative endophthalmitis was 0.17% over 7 years. The mean age of presentation was 5.5 years (range from 7 months to 16 years and 9 months), from 3 days-78 months post operatively. In all, 11/13 had at least one glaucoma procedure. Microbiology results showed growth in 8/13. Most isolates were Gram-positive bacteria but Gram-negatives were also isolated and in one case Candida from a conjunctival swab. The antibiotic regime varied depending on age, organism identified and sensitivities. In all, 9/13 had hand movement or worse vision after treatment. CONCLUSION: Paediatric endophthalmitis may present to any paediatric/general ophthalmologist. It is a rare but devastating condition with poor visual prognosis, requiring prompt recognition and aggressive management. Previous glaucoma surgery is a long-term risk factor in our local paediatric population. Based on our study, an evidence-based protocol for management is proposed in order to improve outcomes.

Enhancement of cellular activity in hyperglycemic mice dermal wounds dressed with chitosan-alginate membranes.

The use of specially designed wound dressings could be an important alternative to facilitate the healing process of wounds in the hyperglycemic state. Biocompatible dressings combining chitosan and alginate can speed up wound healing by modulating the inflammatory phase, stimulating fibroblast proliferation, and aiding in remodeling phases. However, this biomaterial has not yet been explored in chronic and acute lesions of diabetic patients. The aim of this study was to evaluate the effect of topical treatment with a chitosan-alginate membrane on acute skin wounds of hyperglycemic mice. Diabetes mellitus was induced by streptozotocin (60 mg · kg-1 · day-1 for 5 days, intraperitoneally) and the cutaneous wound was performed by removing the epidermis using a surgical punch. The results showed that after 10 days of treatment the chitosan and alginate membrane (CAM) group exhibited better organization of collagen fibers. High concentrations of interleukin (IL)-1α, IL-1ß, granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α) were detected in the first and second days of treatment. G-CSF and TNF-α level decreased after 5 days, as well as the concentrations of TNF-α and IL-10 compared with the control group (CG). In this study, the inflammatory phase of cutaneous lesions of hyperglycemic mice was modulated by the use of CAM, mostly regarding the cytokines IL-1α, IL-1ß, TNF-α, G-CSF, and IL-10, resulting in better collagen III deposition. However, further studies are needed to better understand the healing stages associated with CAM use.

Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque.

INTRODUCTION: Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with bacteria. Diagnosis is achieved retrospectively by clinical observation of attachment loss. Predicting disease progression would allow for targeted preventive therapy. The aim of this study was to monitor disease progression in patients on a maintenance program and determine the levels of specific bacteria in subgingival plaque samples and then examine the ability of the clinical parameters of disease and levels of specific bacteria in the plaque samples to predict disease progression. METHODS: During a 12-month longitudinal study of 41 subjects, 25 sites in 21 subjects experienced disease progression indicated by at least 2 mm of clinical attachment loss. Real-time polymerase chain reaction was used to determine the levels of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in subgingival plaque samples. RESULTS: No clinical parameters were able to predict periodontal disease progression. In sites undergoing imminent periodontal disease progression within the next 3 months, significant partial correlations were found between P. gingivalis and T. forsythia (r = 0.55, P < 0.001) and T. denticola and T. forsythia (r = 0.43, P = 0.04). The odds of a site undergoing imminent periodontal disease progression increased with increasing levels of P. gingivalis and T. denticola. CONCLUSION: Monitoring the proportions of P. gingivalis and T. denticola in subgingival plaque has the potential to help identify sites at significant risk for progression of periodontitis, which would assist in the targeted treatment of disease.

Anticariogenic efficacy of a saliva biomimetic in head-and-neck cancer patients undergoing radiotherapy.

BACKGROUND: The aim of this study was to investigate the effect of treatment with the saliva biomimetic, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and SnF2 /NaF compared with SnF2 /NaF alone on coronal surface caries progression in head-and-neck cancer patients undergoing radiotherapy. METHODS: Twenty-four participants were randomized into two groups. Both groups used 0.4% SnF2 gel and a 0.32% NaF toothpaste; the test group also applied a crème containing 10% CPP-ACP three times daily while the control group used an identical crème without CPP-ACP (placebo). Resting saliva flow rate and saliva fluoride concentrations were determined. Caries status was assessed using ICDASII at baseline and 12-weeks postradiotherapy. Data were statistically analysed using a linear mixed effects model. RESULTS: Both groups showed significantly reduced resting saliva flow rate (P < 0.001) postradiotherapy. There were no significant differences in flow rates and fluoride concentration between groups. The CPP-ACP group exhibited a significant (P < 0.05) 51% reduction in coronal surface caries progression compared with the placebo group. CONCLUSION: Resting salivary flow rate was significantly reduced in head-and-neck cancer patients following radiotherapy and use of CPP-ACP with SnF2 /NaF significantly lowered caries progression compared with SnF2 /NaF alone.

The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography.

This study investigated, using digital bitewing radiography, the progression and regression of approximal caries in adolescent subjects chewing a sugar-free gum containing 54 mg CPP-ACP relative to the identical gum without CPP-ACP. 2,720 subjects from 29 schools were randomly assigned to one of the two gums and were instructed to chew their assigned gum for 3 x 10 min/day, with one session supervised on school days, over the 24-month study period. Standardized digital bitewing radiographs were taken at the baseline and 24-month clinical examinations for each subject. The radiographs, scored by a single examiner, were assessed for approximal surface dental caries at both the enamel and dentine level. Surface level transitions were scored using a transition matrix. Caries progression or regression was analysed using proportional-odds ordered logistic regression modelling of the transition scores at the tooth surface level. There was a statistically significant difference in the frequency distributions of the transition scores between the two gum groups (OR = 0.82, p = 0.03). For subjects chewing the CPP-ACP gum the odds of a surface experiencing caries progression were 18% less than those of a surface experiencing caries progression for subjects chewing the control gum. In conclusion, the 54 mg CPP-ACP sugar-free gum significantly slowed progression and enhanced regression of approximal caries relative to a control sugar-free gum in a 24-month clinical trial.

Reducing Potentially Preventable Dental Hospitalizations of Young Children: A Community-Level Analysis.

An increasing number of Australians are being admitted to hospitals and day procedure centers to have dental treatment under a dental general anesthetic (DGA). Children younger than 2 y are having DGAs. These operations are costly and, although there have been improvements in safety, are not without risk. Most DGAs in children are to treat dental caries and have been defined as potentially preventable dental hospitalizations (PPDHs). This article reports on an analysis of the impact of access to community water fluoridation (CWF), availability of oral health professionals (OHPs), and socioeconomic status (SES) on PPDHs of 0- to 4-y-olds in 2012-2013 in Victoria, Australia. Data on these variables were obtained at the community (postcode) level. From the negative binomial multivariate analysis, each of the 3 independent variables was independently significantly associated with PPDHs at the postcode level. Children residing in postcodes without CWF on average had 59% higher rates than those with access (incident rate ratio [IRR], 1.59; P < 0.0001), children in postcodes with the lowest level of availability of OHPs had 65% higher rates than those with the highest access (IRR, 1.65; P < 0.0001), and children living in the most disadvantaged SES quintiles had 57% higher rates than children in the most advantaged quintiles (IRR, 1.57; P < 0.0001). There was a stepwise social gradient by SES quintile. In analysis of access to CWF and SES status, children without access to CWF had 86% higher PPDH rates than children with access (IRR, 1.86; P < 0.0001). In summary, no access to CWF, poor availability of OHPs, and lower SES status were independently associated with higher PPDH rates among 0- to 4-y-olds in Victoria at the postcode level. The study highlights the importance of considering 3 interacting factors-access to CWF, access to OHPs, and SES-in efforts to reduce PPDH rates in young children. Knowledge Transfer Statement: Extending access to water fluoridation, increasing the availability of dental services, and raising disadvantaged families' socioeconomic status are each likely to decrease the rate of dental general anesthetics in young children.

Hypoglycaemic unawareness: A systematic review of qualitative studies of significant others' (SO) supportive interventions for patients with diabetes mellitus.

BACKGROUND: Hypoglycemia unawareness (HU) has been attributed to both a downward shift in central nervous system (CNS)-triggered sympatho-adrenal responses to low glycaemic thresholds and a subsequent loss of adrenergic symptoms, which, in addition, to cerebral cortex adaptations permit normal function under hypoglycaemic conditions. Both of these mechanisms are brought about by recurring hypoglycemic events (hypoglycemia-associate autonomic failure, HAAF). This can contribute to repetitive cycles of increasingly severe hypoglycaemia, the consequences of which have considerable impact on relatives and significant others (SO) when providing care to patients with diabetes. METHODS: A Systematic Review (SR) of 639 qualitative studies was carried out in accordance with the Preferred Reporting Items for Systematic Review (PRISMA) principles. The search strategy was developed using MeSH terms for a range of electronic databases: CINAHL, Pubmed, EMBASE, Medline, AMED and ASSIA were systematically searched in order to identify a variety of literature relevant to the review topic. Four duplicate studies were removed and a further 630 studies were excluded due to being irrelevant. Five qualitative studies were retained and analysed. RESULTS: The three resultant findings from the literature appraised were i) Experiences and views of Significant Others' (SO) with adult relatives that have HU ii) Support needs of SO and iii) Health professionals interventions to address SO support needs and improve overall HU care. A clear finding was that SO experience difficulties managing HU and this can impact on the relationships that SO and HU patients have. Support needs of SO highlighted were both educational and psychological in nature, with there being a requirement for additional raised awareness within the wider community. CONCLUSION: It is essential that healthcare professionals offer support, such as teaching and support groups. In addition, providing interventions into improving family knowledge of diabetes and support with regard to psychosocial, behavioural and practical support for the person with diabetes. Moreover, improving resources for families to improve diabetes care. However, as the literature was of a qualitative nature, future recommendations would be quantitative research into these suggested nursing implementations to quantitatively assess their usefulness in practice.

A systematic review and meta-analysis of patient education in preventing and reducing the incidence or recurrence of adult diabetes foot ulcers (DFU).

BACKGROUND: The World Health Organization (WHO) states that diabetic foot ulcers (DFU) are associated with disability, death among patients with diabetes and substantial costs, if not prevented or managed effectively. The aim here is to examine the effectiveness of patient education in preventing and reducing the incidence or recurrence of adult DFU and amputation. METHODS: A systematic review and meta-analysis of randomised clinical trials (RCTs) in adults aged 18+ who have diabetes mellitus (type 1 or type 2) or DFU. CINAHL, EMBASE, MEDLINE, PSYCINFO, Cochrane Library and Evidence-Based Nursing, National Library for Health, Medica and Google Scholar were searched. Only English language studies were considered. Databases were searched from their inception to September 2017. FINDINGS: Six RCTs met the inclusion criteria. Only five RCTs reported on the incidence of DFU whilst only two reported on amputation rates. There was no advantage of combining different educational approaches in preventing/reducing DFU, relative risk (RR) of 0.50 (95%CI 0.21, 1.17) (P = 0.11). Two RCTs based on foot care education alone were compared with usual care; the result showed a non-significant effect (P = 0.57) with high heterogeneity of 77%.Analysis based on intensive versus brief educational approach showed a statistically reduced risk of incidence of DFU in the intervention group when compared to the control group; (RR, 0.37, 95%CI 0.14, 1.01) (P = 0.05) with high heterogeneity of 91%. INTERPRETATION: The intensive educational intervention was associated with reduced incidence of DFU.

Quality of life and functional vision in children treated for cataract-a cross-sectional study.

PurposeChildren with cataract and their families face intensive medical and surgical management, with numerous hospital attendances, topical medications, and surgical procedures, as well as uncertainty about the child's future visual ability, education, and independence. Little is known about the impact on functional visual ability, vision-, and health-related quality of life (VR-, HR-QoL).Patients and methodsSeventy two children aged 2-16 years (mean 8.45, SD 4.1) treated for developmental or secondary cataract and their parents/carers completed three validated instruments measuring functional visual ability, VR-, and HR-QoL: the Cardiff Visual Ability Questionnaire for Children (CVAQC), Impact of Vision Impairment for Children (IVI-C), and PedsQL V 4.0.ResultsAll scores are markedly reduced: median (interquartile range (IQR)) CVAQC score -1.42 (-2.28 to -0.03), mean (SD) IVI-C score 65.67 (16.91), median (IQR) PedsQL family impact score 75 (56.94-88.19), parent report 71.74 (51.98-88.5), self-report 76.09 (61.96-89.13). Psychosocial PedsQL subscores are lower than physical subscores. Parent-completed tools (PedsQL family and parent report) state greater impact on HR-QoL than tools completed by children/young people, particularly in teenagers. Older children/young people have higher functional visual ability scores than younger children.ConclusionsCataract has a marked a long-term impact on functional visual ability and quality of life of children and young people, with HR-QoL affected to degrees reported in children with severe congenital cardiac defects or liver transplants.