Randomised controlled trial of an online cognitive training program in school-aged children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) experience deficits in nonverbal reasoning. The SMART online cognitive intervention has been associated with gains in IQ and nonverbal IQ in previous studies in typically developing school-aged children and children experiencing learning difficulties. AIM: To assess the efficacy of an online cognitive intervention in school-aged children with CP. METHODS AND PROCEDURES: 21 children with CP (male n = 17; 76.2%), mean age 9 y 8 m, SD 1 y 1 month (range 8 y 3 m to 12 y 6 m) were randomised into the intervention group (n = 9) or a waitlist control group. A mixed-methods approach with an explanatory sequential design was used, with a randomised controlled trial followed by qualitative interviews. Participants were assessed on measures of intelligence, academic ability, attention and executive functioning, and social-emotional functioning at baseline, then after completing the training, or the waitlist period. Analyses included ANCOVAs and paired samples t tests. Semi-structured interviews explored participants' experiences with the training. RESULTS AND OUTCOMES: Training completion was low with a mean of 16.9 modules completed out of 55 available. No significant effect of training was found for the primary outcome of intelligence, or for any secondary outcomes. Participants reported barriers and facilitators for accessing the program. IMPLICATIONS: Cognitive training programs addressing relational framing ability may require significant modifications before they can be effectively tested with children with CP.

Cognition and learning difficulties in a representative sample of school-aged children with cerebral palsy.

BACKGROUND: Nearly half of all children with CP experience intellectual impairment, with impacts on academic achievement. AIMS: To assess cognitive and academic functioning for primary-school aged children with CP METHODS AND PROCEDURES: This population-based cohort study assessed 93 participants (male n = 62; mean = 9 years 9 months, SD 1 y 1.8 months) on measures of fluid and crystallised intelligence (Raven's Coloured Progressive Matrices, Peabody Picture Vocabulary Test) and academic achievement (Wechsler Individual Achievement Test). Analyses included t-tests, Pearson's chi-square and regression. OUTCOMES AND RESULTS: 41 (44.1%) children met criteria consistent with intellectual developmental disorder. Academic skills were significantly below population means on word reading (M= 85.4, SD = 19.3), t(66) = -6.2, p < .001; spelling (M=83.3, SD=19.7) t(65) = -6.87, p < .001; and numerical operations (M=72.9, SD=21.7) Z = 66.0, p < .001. Cognitive ability was associated with GMFCS level (χ² (1, N = 93) = 16.15, p < .001) and diagnosis of epilepsy (χ² (2, N = 93) = 11.51 p = .003). Crystallised and fluid intelligence together accounted for 65% of the variance in word reading, 56% in spelling and 52% in numerical operations. IMPLICATIONS: Many children with CP experience academic challenges. Screening is recommended for all children with CP and full psychoeducational assessment undertaken when children with CP experience academic difficulties.

The psychological characteristics of people consuming vegetarian, vegan, paleo, gluten free and weight loss dietary patterns.

OBJECTIVE: Previous research has identified several psychological factors associated with dietary restriction but has focused almost exclusively on the subcategory of people following a weight loss diet. Little is known about the psychological factors associated with other kinds of restrictive dietary patterns. Furthermore, it remains unclear whether the identified psychological characteristics of dieters (e.g. elevated disordered eating behaviours, poor well-being) are a cause of dieting, follow from calorie restriction or are the result of cognitive restraint. METHODS: This study conducted the first direct comparison of people (N = 393) following five different restrictive dietary patterns (vegetarian, vegan, gluten free, paleo and weight loss) as well as a comparison group who were not following a specific dietary pattern. RESULTS: The weight loss group had more negative psychological characteristics than all other groups, reporting the highest levels of eating disorder symptoms (M = 1.50), food cravings (M = 69.39), emotional eating (M = 2.97) and negative affect (M = 19.72). By contrast, several of the other restrictive dietary groups showed a number of psychological strengths, relative to the comparison group. This was particularly apparent among the paleo group, who reported the lowest levels of eating disorder symptoms (M = 0.74), food cravings (M = 47.63), emotional eating (M = 2.30) and negative affect (M = 14.81). By contrast, people following vegetarian and gluten free diets were largely the same as the non-restricted comparison group in their psychological characteristics. CONCLUSIONS: People adhering to different dietary patterns showed stark differences in their psychological characteristics. Indeed, some restrictive dietary patterns (paleo and vegan) were associated with more positive psychological characteristics than seen in an unrestricted comparison group. This suggests that the psychological risk factors seen in weight loss dieters are not attributable to a restrictive dietary regimen per se.

Autophagic dysfunction and autophagosome escape in the mdx mus musculus model of Duchenne muscular dystrophy.

AIM: Duchenne muscular dystrophy is caused by the absence of functional dystrophin protein and results in a host of secondary effects. Emerging evidence suggests that dystrophic pathology includes decreased pro-autophagic signalling and suppressed autophagic flux in skeletal muscle, but the relationship between autophagy and disease progression is unknown. The purpose of this investigation was to determine the extent to which basal autophagy changes with disease progression. We hypothesized that autophagy impairment would increase with advanced disease. METHODS: To test this hypothesis, 7-week-old and 17-month-old dystrophic diaphragms were compared to each other and age-matched controls. RESULTS: Changes in protein markers of autophagy indicate impaired autophagic stimulation through AMPK, however, robust pathway activation in dystrophic muscle, independent of disease severity. Relative protein abundance of p62, an inverse correlate of autophagic degradation, was dramatically elevated with disease regardless of age. Likewise, relative protein abundance of Lamp2, a lysosome marker, was decreased twofold at 17 months of age in dystrophic muscle and was confirmed, along with mislocalization, in histological samples, implicating lysosomal dysregulation in this process. In dystrophic muscle, autophagosome-sized p62-positive foci were observed in the extracellular space. Moreover, we found that autophagosomes were released from both healthy and dystrophic diaphragms into the extracellular environment, and the occurrence of autophagosome escape was more frequent in dystrophic muscle. CONCLUSION: These findings suggest autophagic dysfunction proceeds independent of disease progression and blunted degradation of autophagosomes is due in part to decreased lysosome abundance, and contributes to autophagosomal escape to the extracellular space.

Congenital syphilis in neonates with nonreactive nontreponemal test results.

OBJECTIVE: Infants whose mothers had syphilis during pregnancy were studied to determine how often exposed newborns with normal physical examinations and nonreactive nontreponemal serologic tests had abnormal laboratory or radiographic studies. STUDY DESIGN: Retrospective analysis of prospectively collected data from infants born to mothers with syphilis and had a normal examination and a nonreactive nontreponemal test. Some infants had IgM immunoblotting, PCR testing or rabbit infectivity testing (RIT) performed. RESULTS: From 1984 to 2002, 115 infants had a nonreactive serum Venereal Disease Research Laboratory (VDRL)/rapid plasma reagin (RPR) test and a normal physical examination at birth. Among 87 infants born to mothers who had untreated syphilis, 4 had a positive serum IgM immunoblot or PCR test, but none had spirochetes recovered by RIT. Two infants had anemia, one had an elevated serum alanine aminotransferase concentration and one with Down's syndrome had direct hyperbilirubinemia. Among 14 infants born to mothers treated <4 weeks before delivery, none had abnormal laboratory or radiographic tests, although 1 of 11 had a reactive serum IgM immunoblot. Among 14 infants born to mothers treated ⩾4 weeks before delivery, none had abnormal laboratory or radiographic tests. CONCLUSION: Newborns with normal physical examination and nonreactive nontreponemal test results are unlikely to have abnormalities detected on conventional laboratory and radiographic testing.

Reconciling agriculture, carbon and biodiversity in a savannah transformation frontier.

Rapidly rising populations and likely increases in incomes in sub-Saharan Africa make tens of millions of hectares of cropland expansion nearly inevitable, even with large increases in crop yields. Much of that expansion is likely to occur in higher rainfall savannas, with substantial costs to biodiversity and carbon storage. Zambia presents an acute example of this challenge, with an expected tripling of population by 2050, good potential to expand maize and soya bean production, and large areas of relatively undisturbed miombo woodland and associated habitat types of high biodiversity value. Here, we present a new model designed to explore the potential for targeting agricultural expansion in ways that achieve quantitatively optimal trade-offs between competing economic and environmental objectives: total converted land area (the reciprocal of potential yield); carbon loss, biodiversity loss and transportation costs. To allow different interests to find potential compromises, users can apply varying weights to examine the effects of their subjective preferences on the spatial allocation of new cropland and its costs. We find that small compromises from the objective to convert the highest yielding areas permit large savings in transportation costs, and the carbon and biodiversity impacts resulting from savannah conversion. For example, transferring just 30% of weight from a yield-maximizing objective equally between carbon and biodiversity protection objectives would increase total cropland area by just 2.7%, but result in avoided costs of 27-47% for carbon, biodiversity and transportation. Compromise solutions tend to focus agricultural expansion along existing transportation corridors and in already disturbed areas. Used appropriately, this type of model could help countries find agricultural expansion alternatives and related infrastructure and land use policies that help achieve production targets while helping to conserve Africa's rapidly transforming savannahs.This article is part of the themed issue 'Tropical grassy biomes: linking ecology, human use and conservation'.

Can the optimal cervical length for placing ultrasound-indicated cerclage be identified?

OBJECTIVE: To assess a continuum of cervical length (CL) cut-offs for the efficacy of ultrasound-indicated cerclage in women with previous spontaneous preterm birth (PTB). METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of ultrasound-indicated cerclage for the prevention of PTB in high-risk women. The efficacy of cerclage for preventing recurrent PTB < 35, < 32 and < 24 weeks' gestation was assessed using multivariable logistic regression analysis. Odds ratios (ORs) and CIs were estimated for a range of CL cut-offs using bootstrap regression. The 2.5(th) and 97.5(th) percentiles of bootstrapped ORs determined the CIs. Results were illustrated using smoothed curves superimposed on estimated ORs by CL cut-off. RESULTS: Of 301 women with a CL < 25 mm, 142 underwent ultrasound-indicated cerclage and 159 did not have cerclage placement. The few cases with CL < 10 mm limited the evaluation to CL cut-offs between < 10 mm and < 25 mm. For PTB < 35 weeks, ORs in women with a cerclage and CL < 25 mm were statistically significantly lower than in those without cerclage, and efficacy was maintained at smaller CL cut-offs. Results were similar for PTB < 32 weeks. For PTB < 24 weeks, results differed, with ORs increasing toward unity (no benefit), with wide CIs, for CL cut-offs between < 10 mm and < 15 mm, attributed to the small number of births < 24 weeks. CONCLUSIONS: The efficacy of ultrasound-indicated cerclage in women with previous spontaneous PTB varies by action point CL cut-off and by PTB gestational age of interest. Cerclage significantly reduces the risk of PTB < 35 and < 32 weeks, at CL cut-offs between < 10 mm and < 25 mm, with the greatest reduction at shorter CL, affirming that women with prior spontaneous PTB and a short CL are appropriate candidates for ultrasound-indicated cerclage. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Effect of body mass index on maternal morbidity following peripartum hysterectomy.

The objective of this study was to estimate the impact of maternal body mass index (BMI) on maternal morbidity following unscheduled peripartum hysterectomy. A retrospective cohort study of consecutive peripartum hysterectomies at our institution from 1988 through 2012; scheduled hysterectomies were excluded. Medical records were reviewed and maternal, foetal and surgical data collected for each subject. Maternal BMI was categorized by the National Institute of Health classifications for overweight and obese. Statistical analyses included evaluation for trend. A total of 360,774 women delivered at Parkland Hospital during the study period with 665 (1.8 per 1000 deliveries) unscheduled peripartum hysterectomies performed. BMI was available for 635 women. Gestational diabetes, chronic hypertension and pregnancy-related hypertension were significantly higher in all three obesity categories, P = < 0.01. Post-partum complications, such as venous thrombosis and composite surgical morbidity did not differ among BMI groups. Estimated blood loss and units transfused did not differ across the BMI categories, P = 0.42 and P = 0.38, respectively. Increasing BMI was associated with longer surgical times and more wound infections, P = 0.01. These complications should be considered when approaching a peripartum hysterectomy in patients with obesity.

Association between body mass index and pregnancy outcome in a randomized trial of cerclage for short cervix.

OBJECTIVE: To evaluate whether increasing body mass index (BMI) alters the efficacy of ultrasound-directed cerclage in women with a history of preterm birth. METHODS: This was a planned secondary analysis of a multicenter trial in which women with a singleton gestation and prior spontaneous preterm birth (17 to 33 + 6 weeks' gestation) were screened for a short cervix by serial transvaginal ultrasound evaluations between 16 and 22 + 6 weeks. Women with a short cervix (cervical length < 25 mm) were randomly assigned to cerclage or not. Linear and logistic regression were used to assess the relationship between BMI and continuous and categorical variables, respectively. RESULTS: Overall, in the screened women (n = 986), BMI was not associated with cervical length (P = 0.68), gestational age at delivery (P = 0.12) or birth at < 35 weeks (P = 0.68). For the cerclage group (n = 148), BMI had no significant effect. For the no-cerclage group (n = 153), BMI was associated with a decrease in gestational age at delivery, with an estimated slope of - 0.14 weeks per kg/m(2) (P = 0.03; including adjustment for cervical length). This result was driven primarily by several women with BMI > 47 kg/m(2) . CONCLUSION: In women at high risk for recurrent preterm birth, BMI was not associated with cervical length or gestational age at birth. BMI did not appear to adversely affect ultrasound-indicated cerclage.

Extending the clinical research network approach to all of healthcare.

The development of Clinical Research Networks (CRN) has been central to the work conducted by Health Departments and research funders to promote and support clinical research within the NHS in the UK. In England, the National Institute for Health Research has supported the delivery of clinical research within the NHS primarily through CRN. CRN provide the essential infrastructure within the NHS for the set up and delivery of clinical research within a high-quality peer-reviewed portfolio of studies. The success of the National Cancer Research Network is summarized in Chapter 5. In this chapter progress in five other topics, and more recently in primary care and comprehensively across the NHS, is summarized. In each of the 'topic-specific' networks (Dementias and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health, Stroke) there has been a rapid and substantial increase in portfolios and in the recruitment of patients into studies in these portfolios. The processes and the key success factors are described. The CRN have worked to support research supported by pharmaceutical, biotechnology and medical device companies and there has been substantial progress in improving the speed, cost and delivery of these 'industry' studies. In particular, work to support the increased speed of set up and delivery of industry studies, and to embed this firmly in the NHS, was explored in the North West of England in an Exemplar Programme which showed substantial reductions in study set-up times and improved recruitment into studies and showed how healthcare (NHS) organizations can overcome delays in set up times when they actively manage the process. Seven out of 20 international studies reported that the first patient to be entered anywhere in the world was from the UK. In addition, the CRN have supported research management and governance, workforce development and clinical trials unit collaboration and coordination. International peer reviews of all of the CRN have been positive and resulted in the continuation of the system for a further 5 years in all cases.

Timing of mid-trimester cervical length shortening in high-risk women.

OBJECTIVE: To examine the natural history of cervical length shortening in women who had experienced at least one prior spontaneous preterm birth at between 17+0 and 33+6 weeks' gestation. METHODS: This was an analysis of prerandomization data from the multicenter Vaginal Ultrasound Cerclage Trial. Serial cervical length was measured by transvaginal sonography in 1014 high-risk women at 16+0 to 22+6 weeks. We performed survival analyses in which the outcome was cervical length shortening<25 mm and data were censored if this did not occur before 22+6 weeks' gestation. The incidence of cervical length shortening and the time to shortening were compared for women whose earliest prior preterm birth was in the mid-trimester, defined as <24 weeks, vs. those at weeks 24-33. Similar comparisons were performed based on each patient's most recent birth history. RESULTS: Time to cervical length shortening by survival analysis was significantly shorter (hazard ratio (HR)=2.2, P<0.0001) and the relative risk (RR) of shortening significantly higher (RR=1.8, P<0.0001) for women whose earliest prior spontaneous preterm birth was at <24 weeks. A larger effect was observed for women whose most recent birth was at <24 weeks (HR=2.8, P<0.0001; RR=2.1, P<0.0001). The observed hazard ratios remained significant after adjusting for confounders in a multivariable Cox proportional hazards model. CONCLUSION: Women with a prior spontaneous preterm birth at <24 weeks are at a higher risk of cervical shortening, and do so at a higher rate and at an earlier gestational age, than do women with a later preterm birth history.

Laparoscopic resection for colorectal cancer.

BACKGROUND: This study examined one surgeon's practice to determine the place of laparoscopic colorectal cancer surgery. METHODS: Some 365 patients undergoing elective colorectal cancer resection (219 colonic, 146 rectal) were studied prospectively. Early (1994-1997; 104 patients), middle (1998-2001; 112) and late (2002-2005; 149) cohorts were analysed with respect to suitability for laparoscopic surgery, conversion and outcome. RESULTS: Forty-six of 135 patients undergoing open resection were suitable for laparoscopic surgery but randomized to open surgery. The proportion of attempted laparoscopic resections (35.6, 65.2 and 80.6 per cent in early, middle and late cohorts) and patients thought suitable for laparoscopic resection (37.5, 87.5 and 94.0 per cent respectively; P = 0.001) increased over time. Independent predictors of conversion were rectal cancer surgery (odds ratio (OR) 3.12 versus colonic surgery) and body mass index 28 kg/m(2) or more (OR 3.87). Conversion was necessary in all five patients with a threatened margin predicted by preoperative magnetic resonance imaging. After exclusion of these patients the conversion rate in the late cohort was 8.7 per cent. During the same period, inclusion of 20 patients who were suitable for laparoscopic surgery but underwent open resection meant that 135 (90.6 per cent) of 149 patients were actually suitable for laparoscopic resection. CONCLUSION: With experience, laparoscopic surgery is feasible in around 90 per cent of elective colorectal cancer resections.

The influence of an enhanced recovery programme on clinical outcomes, costs and quality of life after surgery for colorectal cancer.

OBJECTIVE: Optimizing peri-operative care using an enhanced recovery programme improves short-term outcomes following colonic resection. This study compared a prospective group of patients undergoing resection of colorectal cancer within an enhanced recovery programme, with a prospectively studied historic cohort receiving conventional care. PATIENTS AND METHODS: Sixty patients underwent elective resection within an enhanced recovery programme (ERP). This incorporated pre-operative counselling, epidural analgesia, early feeding and mobilization. Clinical outcomes were compared with 86 prospectively studied historic control patients receiving conventional care (CC). All patients completed EORTC QLQ-C30, QLQ-CR38 and health economics questionnaires up to three months after surgery. RESULTS: Baseline clinical data were similar in both groups. Postoperative hospital stay was significantly reduced in the ERP, with patients staying 49% as long as those in the CC group including convalescent hospital stay (95% CI 39% to 61%P < 0.001). There were no differences in the number of complications, readmissions or re-operations. There were no significant differences in quality of life or health economic outcomes. CONCLUSION: Patients undergoing colorectal resection within an ERP stay in hospital half as long as those receiving conventional care, with no increased morbidity, deterioration in quality of life or increased cost.

Stepping Stones Triple P: a pilot study to evaluate acceptability of the program by parents of a child diagnosed with an Autism Spectrum Disorder.

The experience of parents of children with Autism Spectrum Disorder (ASD) in standard parenting programs has not been researched, although anecdotal evidence suggests that they do not find them acceptable. Forty-two parents of children with ASD were asked to view a DVD explaining individual parenting strategies from Stepping Stones, a new branch of the Triple P program targeted specifically at parents of children with disabilities. Parents were asked to rate each strategy for acceptability, usability and behavioural intention, i.e., their intention to use the strategy. Additionally, parental attributions and parental perceived control were explored as possible barriers to positive evaluations of Stepping Stones parenting strategies. A focus group of parents was used to gather more detailed parent response to the program. Parent responses to the program were generally positive and attribution of the child's behaviour to uncontrollable factors was found to predict higher ratings of usability. The results were interpreted within the context of Weiner's attributional theory and the theory of reasoned action. The limitations of this study and suggestions for future research are discussed.

Tumour morphology as a predictor of outcome after local excision of rectal cancer.

BACKGROUND: The aim of this study was to determine whether the morphology of rectal cancer predicts outcome following treatment by local excision, and whether morphology should therefore be added to the criteria presently used for case selection. METHODS: The hospital notes and histological findings of 91 patients who had undergone a local surgical procedure for rectal cancer were reviewed retrospectively. Eight patient and tumour characteristics including morphology were analysed with respect to 5-year survival, local recurrence and cancer-specific death within 5 years. Morphology was divided into four types: polypoid, sessile, ulcerated and flat raised. RESULTS: Survival and local recurrence were significantly better for patients with exophytic (polypoid and sessile) carcinomas than for those with non-exophytic (ulcerated and flat raised) lesions. Multivariate logistic regression analysis showed that age, depth of invasion, lymphatic invasion and venous invasion were significant predictors of outcome. The exophytic group included significantly more stage T1 and fewer T2 and T3 cancers, and a significantly smaller proportion of tumours that showed venous and lymphatic invasion than the non-exophytic group. CONCLUSION: Morphology is a clinical guide to prognosis after local excision. Non-exophytic cancers are associated with high-risk histopathological features that render tumours of this type unsuitable for local excision.

Hepatotoxicity with antiretroviral treatment of pregnant women.

BACKGROUND: Hepatotoxicity in adults with human immunodeficiency virus (HIV) infection has been associated with all classes of antiretroviral drugs and coinfection with hepatitis B and C virus. We treated two HIV-infected pregnant women in whom hepatotoxicity developed after initiating antiretroviral therapy. CASES: The first woman developed icterus, jaundice, hyperbilirubinemia, and elevated serum aminotransferase levels approximately 5 months after beginning combination antiretroviral therapy with zidovudine, lamivudine, and efavirenz. Serum aminotransferase abnormalities improved after discontinuation of antiretroviral medications. The second woman had similar symptoms and laboratory abnormalities 3 months after initiation of zidovudine, lamivudine, and nelfinavir. Despite initial improvement after discontinuing her antiretroviral medications, fulminant hepatic failure developed and she died. Both patients tested negative for hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus. There was no history of illicit drug use, alcohol use, or blood transfusions in either case. CONCLUSION: We emphasize the need for careful monitoring for hepatotoxicity after initiation of antiretroviral therapy.

A randomized trial that compared oral cefixime and intramuscular ceftriaxone for the treatment of gonorrhea in pregnancy.

OBJECTIVE: The purpose of this study was to evaluate prospectively the Centers for Disease Control recommendations for the treatment of gonococcal infection in pregnancy. STUDY DESIGN: One hundred sixty-one women who were referred with probable endocervical gonorrhea underwent pretreatment endocervical, anal, and oral cultures for Neisseria gonorrhoeae. The women were randomly assigned to receive ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally. Treatment was open and in a 1:1 distribution. There were 95 evaluable patients. The tests of cure cultures were performed 4 to 10 days after treatment. RESULTS: Eighty-six women (91%) had endocervical infection; 39 women (41%) had anal infection, and 11 women (12%) had pharyngeal infection. Fifty of 95 women (53%) had concomitant endocervical chlamydial infection. The overall efficacy was 91 of 95 subjects (95.8%; 95% CI, 89.6%-98.8%). Ceftriaxone was effective in 41 of 43 cases (95%; 95% CI, 84.2%-99.4%), and cefixime was effective in 50 of 52 cases (96%; 95% CI, 86.8%-99.5%). No significant difference was noted in the overall efficacy or by site of infection. Three of the 4 women who experienced treatment failures admitted to unprotected intercourse before their test of cure culture. CONCLUSION: Both intramuscular ceftriaxone 125 mg and oral cefixime 400 mg appear to be effective for the treatment of gonococcal infection in pregnancy.

New roles and relationships in the NHS--barriers to change.

The incoming Labour Government's vision for reforming the NHS in Scotland was outlined in the White Paper Designed to Care. While bearing similarities to the proposals outlined for the rest of the UK, it also had distinctive differences. Organisational structures, roles, and relationships between the different parts of the NHS were to be fundamentally altered, particularly in primary and community care. This paper reports upon a series of interviews undertaken across several Health Board areas, with key stakeholders involved in the primary and community sectors. These interviews were intended to examine the development and evolution of the new organisational arrangements, and to identify potential barriers to the successful implementation of Designed to Care. Several barriers and sources of institutional resistance to the new roles and relationships were found during this study, and are discussed. Suggestions upon how these may be overcome and implementation improved are then made.