The Greater Manchester Child Friendly Dental Practice Scheme: Using a Transformational Commissioning Approach to Align Paediatric Dental Service Provision with Childhood Oral Health Needs in Greater Manchester.

In response to the impact of the COVID-19 pandemic on access to already oversubscribed specialist paediatric dental services, a pilot of an enhanced primary care paediatric dental pathway, known as the Child Friendly Dental Practice (CFDP) scheme, was commissioned by the Greater Manchester Health and Social Care Partnership. Supported by a transformational commissioning approach, the ambition of the CFDP pilot was to manage or stabilise the oral health of high-need paediatric patients who had been referred to specialist dental services within Community or Hospital Dental Service settings, through timely access to primary care clinicians who were confident and experienced in treating children. The theory of change of the CFDP pilot proposed that rapid access to enhanced primary dental care would reduce the need for onward referral to specialist paediatric dental services, whilst also stabilising the oral health of children who require more complex management in specialist services. A formative evaluation of the phase one pilot implementation of the CFDP Scheme has demonstrated the potential of the CFDP Scheme to improve access to dental services for paediatric patients referred from their General Dental Practitioner. Comparison of waiting times between the CFDP pathway and the standard paediatric dental referral pathway have revealed substantially reduced waiting times to access care along the CFDP pathway, while less than 30% of those who attended CFDPs required onward referral to specialist paediatric dental services. Encouragingly, similar attendance and treatment completion rates were noted among patients from all levels of socio-economic deprivation, reducing concerns regarding the potential for service-based interventions to increase oral health inequalities. Following successful completion of the phase one pilot implementation and evaluation, the CFDP Scheme has now been rolled out across all localities in Greater Manchester as part of a second phase pilot implementation. Public Health Competencies; Equitable healthcare provision, Partnership working, Evidence-based public health, Systems thinking, Transformational commissioning, Healthcare evaluation.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Modifiable predictors of depression following childhood maltreatment: a systematic review and meta-analysis.

Although maltreatment experiences in childhood increase the risk for depression, not all maltreated children become depressed. This review aims to systematically examine the existing literature to identify modifiable factors that increase vulnerability to, or act as a buffer against, depression, and could therefore inform the development of targeted interventions. Thirteen databases (including Medline, PsychINFO, SCOPUS) were searched (between 1984 and 2014) for prospective, longitudinal studies published in English that included at least 300 participants and assessed associations between childhood maltreatment and later depression. The study quality was assessed using an adapted Newcastle-Ottawa Scale checklist. Meta-analyses (random effects models) were performed on combined data to estimate the effect size of the association between maltreatment and depression. Meta-regressions were used to explore effects of study size and quality. We identified 22 eligible articles (N=12 210 participants), of which 6 examined potential modifiable predictors of depression following maltreatment. No more than two studies examined the same modifiable predictor; therefore, it was not possible to examine combined effects of modifiable predictors with meta-regression. It is thus difficult to draw firm conclusions from this study, but initial findings indicate that interpersonal relationships, cognitive vulnerabilities and behavioral difficulties may be modifiable predictors of depression following maltreatment. There is a lack of well-designed, prospective studies on modifiable predictors of depression following maltreatment. A small amount of initial research suggests that modifiable predictors of depression may be specific to maltreatment subtypes and gender. Corroboration and further investigation of causal mechanisms is required to identify novel targets for intervention, and to inform guidelines for the effective treatment of maltreated children.

Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.

We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.

Cognitive styles and future depressed mood in early adulthood: the importance of global attributions.

BACKGROUND: Cognitive theories of depression suggest that beliefs of low self-worth and the tendency to attribute negative events to causes that are global (widespread rather than specific) and stable (will persist rather than change in the future) are associated with the development of depressed mood. Such theories are supported by evidence from prospective studies and have guided the development of successful treatment and prevention strategies such as CBT. However, the relative importance of different psychological constructs within cognitive theories is unknown. This is important to refine cognitive theories and develop more efficient prevention strategies. METHOD: We used prospective data from over 3500 young adults from the Avon Longitudinal Study for Parents and Children (ALSPAC) cohort in the UK to investigate the association between cognitive style, measured by short forms of the Dysfunctional Attitudes Scale (DAS) and Cognitive Styles Questionnaire-Short Form (CSQ-SF) at age 18, and future depressed mood at age 19. Structural equation modelling techniques were used to separate cognitive style constructs. RESULTS: Cognitive styles were associated with future depressed mood, independently of baseline mood, both as measured by the DAS-SF and the CSQ-SF. Of the different CSQ-SF constructs, only global attributions were associated with both baseline and future mood independently of other constructs. LIMITATIONS: The study was subject to attrition and the follow-up was relatively short (10 months). CONCLUSION: The findings suggest that the tendency to attribute negative events specifically to global causes could be particularly important for depression. Reducing global attributions is potentially important in the prevention and treatment of depression.

Invasive fungal infections in paediatric acute myeloid leukaemia.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.

Introducing care pathway commissioning to primary dental care: measuring performance.

Care pathways have been used in a variety of ways: firstly to support quality improvement through standardising clinical processes, but also for secondary purposes, by purchasers of healthcare, to monitor activity and health outcomes and to commission services. This paper focuses on reporting a secondary use of care pathways: to commission and monitor performance of primary dental care services. Findings of a project involving three dental practices implementing a system based on rating patients according to their risk of disease and need for care are outlined. Data from surgery-based clinical databases and interviews from commissioners and providers are reported. The use of both process and outcome key performance indicators in this context is discussed, as well as issues which arise such as attributability of outcome measures and strategic approaches to improving quality of care.

Bullying victimization in youths and mental health problems: 'much ado about nothing'?

Bullying victimization is a topic of concern for youths, parents, school staff and mental health practitioners. Children and adolescents who are victimized by bullies show signs of distress and adjustment problems. However, it is not clear whether bullying is the source of these difficulties. This paper reviews empirical evidence to determine whether bullying victimization is a significant risk factor for psychopathology and should be the target of intervention and prevention strategies. Research indicates that being the victim of bullying (1) is not a random event and can be predicted by individual characteristics and family factors; (2) can be stable across ages; (3) is associated with severe symptoms of mental health problems, including self-harm, violent behaviour and psychotic symptoms; (4) has long-lasting effects that can persist until late adolescence; and (5) contributes independently to children's mental health problems. This body of evidence suggests that efforts aimed at reducing bullying victimization in childhood and adolescence should be strongly supported. In addition, research on explanatory mechanisms involved in the development of mental health problems in bullied youths is needed.

Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies.

There is strong evidence for a genetic contribution to schizophrenia, but the contribution of individual candidate genes remains uncertain. We attempted to replicate a recent meta-analysis that reported an association of the catechol O-methyltransferase (COMT) Val allele with schizophrenia, and suggested that this effect may be moderated by ancestry. We included reports published subsequent to the original meta-analysis, and included a formal test of the moderating effect of ancestry in order to test whether the association operates differently in populations of European ancestry compared to populations of Asian ancestry. A corrected P-value for the 5% significance threshold was employed where appropriate, using Bonferroni's method, and studies that demonstrated departure from Hardy-Weinberg equilibrium among controls were excluded. When all studies were included in a meta-regression, there was evidence for a significant association of COMT Val allele frequency with schizophrenia case status and a significant main effect of ancestry. The interaction of COMT Val allele frequency and ancestry was also significant. However, when only studies that reported allele frequencies that did not depart significantly from Hardy-Weinberg equilibrium among controls were included, these effects were no longer significant. The results of our meta-analysis do not support an association between the COMT Val allele and schizophrenia case status, and do not support recent claims that this association may be moderated by ancestry.

Toxic epidermal necrolysis of the scalp following anticonvulsant use and cranial irradiation.

BACKGROUND: Toxic epidermal necrolysis (TEN) of the scalp is rare but it has been shown to occur in patients who had been given a combination of cranial radiation and anticonvulsant therapies. OBJECTIVE: We present a 62-year-old man who received cranial irradiation following craniotomy for glioblastoma multiforme. After he was prescribed the anticonvulsant phenytoin for postsurgical seizure prophylaxis, the patient developed TEN which began on the scalp before spreading to involve other parts of his body. Our second case was a 55-year-old woman who had been diagnosed with lung carcinoma with metastasis to the brain. She was treated with cranial irradiation and the anticonvulsant carbamazepine. TEN developed first on the scalp and then became generalized. CONCLUSIONS: While the combination of radiation and anticonvulsants leads to an increased risk of developing TEN, cranial irradiation appears to be the localizing factor in the development of TEN of the scalp.

A double-blind, side-by-side comparison study of low fluence long pulse dye laser to coolant treatment for wrinkling of the cheeks.

BACKGROUND: Nonablative laser resurfacing with various lasers and light sources can improve skin texture and fine lines. The 595 nm pulsed dye laser has been reported to improve rhytides through nonablative mechanisms, minimizing the side effects and recovery period associated with traditional ablative resurfacing techniques. OBJECTIVE: The purpose of this study was to investigate the efficacy of the long pulse flashlamp pumped pulsed dye laser (LPDL) in improving rhytides and stimulating collagen synthesis and dermal remodeling. METHODS: The cheeks of 15 women with moderate to severe photoaging were treated on one side with a series of four monthly LPDL treatments, while the contralateral cheek was treated with cryogen coolant only. Clinical grading was performed at monthly intervals for up to 3 months after the fourth LPDL treatment. Skin biopsy before treatment and at 4-6 weeks was also performed for histologic evaluation and staining for type I procollagen. RESULTS: Eleven of 15 patients demonstrated improvement of the laser-treated cheek while only three of 15 patients the demonstrated improvement on the cryogen-treated cheek. A statistically significant (p = 0.0035) improvement in clinical grading of photodamage was noted in the treated side versus the control. In those patients who improved with LPDL treatment, an improvement of 18.1% in the mean pre- and post-treatment clinical grading scores was observed. Histologic evaluation demonstrated an increase in activated fibroblasts with positive procollagen staining on the LPDL-treated cheek. CONCLUSION: The 595 nm LPDL may be used in the treatment of moderate to severe wrinkles. A mild improvement may be expected with minimal to no side effects.

Comparison of the 585 nm pulse dye laser and the short pulsed CO2 laser in the treatment of striae distensae in skin types IV and VI.

BACKGROUND: Striae distensae, or stretch marks, are a very common cosmetic problem. The successful management of stretch marks has long been a source of frustration and curiosity for both the clinician and the researcher. Recent studies suggest lasers may have a role in their management. As yet, no study has reported on the effects of either of these lasers in the treatment of stretch marks on persons with skin types 4 to 6. OBJECTIVE: To assess the efficacy of short pulsed CO2 laser and pulsed dye laser for the treatment of stretch marks in skin types 4, 5, and 6. METHODS: Four patients were initially enrolled in the study. All were female with abdominal stretch marks, present for a range of 8 to 19 years. The patients had skin types ranging from 4 to 6. The test area consisted of a stretch mark long enough to be divided into three contiguous 2 cm sections, labeled A, B, and C. Section A served as the short pulsed CO2 test site, section B served as a control, while section C served as the 585 nm pulsed dye site. Patients were seen for evaluation after 1 week, then every 4 weeks for a total of 20 weeks. Patients were evaluated subjectively by the investigators, and the patients' own self-evaluation was reported as well. RESULTS: Following the 585 nm pulse dye laser, at 20 week follow-up patients with type 4 skin showed no improvement, while type 6 skin showed hyperpigmentation. The short pulsed CO2 test site showed persistent erythema in type 4 skin and marked hyperpigmentation in type 6 skin. CONCLUSIONS: For patients with types 4, 5, and 6 skin, laser treatment of striae should be avoided or used with great caution.

Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study.

BACKGROUND: Melasma is very difficult to treat and often refractory to treatment with topical creams and pigmented-lesion lasers. OBJECTIVE: Pulsed CO2 laser alone is compared with the combination of pulsed CO2 laser followed by Q-switched alexandrite laser in the treatment of dermal-type melasma. This combination is proposed to be effective by first destroying the abnormal melanocytes with the pulsed CO2 laser and then selectively eliminating the dermal melanin with the alexandrite laser. METHODS: Four patients were randomly chosen for each treatment arm. There were multiple follow-up visits for examination by an objective blinded investigator. RESULTS: All patients in the combination laser group showed complete resolution, and two patients in the CO2 laser only group had peripheral hyperpigmentation in the long-term follow-up evaluation. CONCLUSION: These laser therapies are safe, as there was no scarring and no infection. The combination laser therapy was highly effective in removing the hyperpigmentation and all patients in this group showed complete resolution without any peripheral hyperpigmentation.

Collagen fiber orientation as quantified by small angle light scattering in wounds treated with transforming growth factor-beta2 and its neutalizing antibody.

The purpose of this study was determine quantitative differences in collagen fiber orientation in a wound healing model in the presence of transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 antibody. Full-thickness wounds were made in the paravertebral area of two young pigs. Wounds were treated once, topically, with either transforming growth factor-beta2 or anti-transforming growth factor-beta2 antibody, or with methylcellulose gel. Control wounds were left untreated. Tissue biopsies were obtained from each wound on days 7, 14 and 46 post wounding. Tissue sections were stained with hematoxylin and eosin, and collagen fiber preferred orientation was quantified using small angle light scattering. Our results indicated that wounds treated with transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 antibody had a significantly higher degree of orientation of collagen fibers than normal unwounded skin on days 7, 14 and 46 (p < 0.001). Transforming growth factor-beta2- treated wounds had a higher degree of orientation of collagen fibers than control wounds on days 7 and 14 (p < 0.001), and control wounds displayed a higher degree of orientation than wounds treated with anti-transforming growth factor-beta2,3 and normal unwounded skin at all time points (p < 0.001). These results suggest that differences in the dermal collagen degree of orientation correlate with scarring, and show that small angle light scattering can be used quantitatively to assess differences in the collagen fiber architecture of dermal wounds.

Culture of marmoset blastocysts on matrigel: a model of differentiation during the implantation period.

BACKGROUND: The objective was to develop an experimental model for studying the differentiation of trophoblast and inner cell mass (ICM) during the early stages of implantation in primates. METHODS: Marmoset monkey blastocytes were used in these studies. Ovulation was timed by plasma progesterone assays in ovarian cycles initiated by administering a luteolytic agent to mating marmosets. Embryos were recovered from the uterus usually at the eight-cell stage and cultured in minimum essential medium containing fetal calf serum, insulin, and transferrin. The embryos that formed hatched blastocysts by about day 11 after ovulation were transferred for further development in Matrigel-coated culture chambers. After 2, 4, and 6 days of development, two blastocysts were processed at each interval and serially sectioned for light and electron microscopy. RESULTS: All blastocysts adhered to the Matrigel at their embryonic pole within 24 hours. Adherent polar cytotrophoblast was differentiating to syncytiotrophoblast at all time intervals, but syncytium was not detected in mural trophoblast until day 4 after attachment. By day 2 syncytial microvilli and processes had penetrated the Matrigel surface, whereas by days 4 and 6 cytotrophoblast that was differentiating to syncytiotrophoblast had invaded the matrix. Since all blastocysts maintained their structural integrity progressive differentiation of the ICM, endoderm and presumptive mesoderm was observed. A small amniotic cavity was observed at 2 days and by 6 days a distinct cavity separated polarized epiblast and amnion cells. Visceral and parietal endoderm were present at 2 days, and a completed primary yolk sac was observed by 4 days after attachment. In all blastocysts a basal lamina lined the inner surface of mural and polar trophoblast and the basal surface of the differentiating ICM. CONCLUSIONS: The developmental time sequence of the cultured blastocysts closely resembled the time frame reported for marmoset embryos implanting in utero. An effective model for studying trophoblast invasion and differentiation of embryonic germ cell layers has been established.