Individual or Group-based Approach to the Assessment of Preschool Children: A Comparison using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA)

Introduction: It is unclear if the assessment of early child development can be carried out using a group approach, as opposed to individually.&#x0D; Objective: To compare scores obtained from children aged 22 to 26 months assessed either in small groups or individually using the INTERGROWTH-21st Neurodevelopment Assessment  (INTER-NDA), which measures cognition, language, motor skills, behavior, attention and socio-emotional reactivity.&#x0D; Methods: A small group based strategy for administering and scoring the INTER-NDA was developed. Thirty-six preschool children attending four Centros de Cuidado y Atención Infantil of the Sistema Nacional para el Desarrollo Integral de la Familia (DIF) of Mexico were assessed in small groups of three children by a teacher specifically trained in the INTER-NDA. A second teacher, unaware of the group results, assessed the children individually on a different day. The sex, age, weight, length and head circumference of the children at the time of assessment were recorded.&#x0D; Results: INTER-NDA domain scores for group and individual assessments were statistically significantly correlated (range r=0.35 to r=1.00) for all domains except receptive language (r=0.25, p=0.14). Bland-Altman analysis showed agreement between group and individual scores for the language, behavior, attention and socio-emotional reactivity domains, and consistency (but not agreement) between group and individual scores for the cognitive and motor domains. None of the differences between group and individual scores examined were statistically significant, even after adjusting for the children’s age, sex, nutritional status and location of the preschool.&#x0D;  &#x0D; Conclusion: INTER-NDA domain specific scores obtained following group and individual assessment of children aged 22 to 26 months are consistent. It is feasible for trained preschool teachers to administer INTER-NDA at both group and individual level.</jats:p

Incidence of sight-threatening diabetic retinopathy in an established urban screening programme: An 11-year cohort study

Aims: systematic annual screening to detect sight-threatening diabetic retinopathy (STDR) is established in the United Kingdom. We designed an observational cohort study to provide up-to-date data for policy makers and clinical researchers on incidence of key screening endpoints in people with diabetes attending one screening programme running for over 30 years.Methods: all people with diabetes aged ≥12 years registered with general practices in the Liverpool health district were offered inclusion. Data sources comprised: primary care (demographics, systemic risk factors), Liverpool Diabetes Eye Screening Programme (retinopathy grading), Hospital Eye Services (slit lamp biomicroscopy assessment of screen positives).Results: 133,366 screening episodes occurred in 28,384 people over 11 years. Overall incidences were: screen positive 6.7% (95% CI 6.5–6.8), screen positive for retinopathy 3.1% (3.0–3.1), unassessable images 2.6% (2.5–2.7), other significant eye diseases 1.0% (1.0–1.1). 1.6% (1.6–1.7) had sight-threatening retinopathy confirmed by slit lamp biomicroscopy. The annual incidence of screen positive and screen positive for retinopathy showed consistent declines from 8.8%–10.6% and 4.4%–4.6% in 2007/09 to 4.4%–6.8% and 2.3%–2.9% in 2013/17, respectively. Rates of STDR (true positive) were consistently below 2% after 2008/09. Screen positive rates were higher in first time attenders (9.9% [9.4–10.2] vs. 6.1% [6.0–6.2]) in part due to ungradeable images (4.1% vs. 2.3%) and other eye disease (2.4% vs. 0.8%). 4.5% (3.9–5.2) of previous non-attenders had sight-threatening retinopathy. Compared with people with type 2 diabetes, those with type 1 disease demonstrated higher rates of screen positive (11.9% vs. 6.0%) and STDR (6.4% vs. 1.2%). Overall prevalence of any retinopathy was 27.2% (27.0–27.4).Conclusions: in an established screening programme with a stable population screen, positive rates show a consistent fall over time to a low level. Of those who are screen positive, fewer than 50% are screen positive for diabetic retinopathy. Most are due to sight threatening maculopathy. The annual incidence of STDR is under 2% suggesting future work on redefining screen positive and supporting extended intervals for people at low risk. Higher rates of screen positive and STDR are seen in first time attenders. Those who have never attended for screening should be specifically targeted.</p

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Factors controlling the pluripotent state of human embryonic stem cells

In the field of regenerative medicine, human embryonic stem (hES) cells offer the potential to treat degenerative diseases and replace damaged or non-functional tissue. However, it is not fully clear how hES cells retain a pluripotent state or differentiate into specific cell lineages. Although most of previous research has found that various proteins are responsible for the balance in hES cell maintenance and differentiation, there is mounting evidence for non-coding RNAs as important players in this task. Data from our laboratory shows that there are genes that encode for variants of the non-coding RNA U1 small nuclear (sn)RNA, a key component of the spliceosome. These variant (v)U1 snRNA genes are transcriptionally active and differentially expressed. Moreover, interfering with the activity of a specific vU1 snRNA affects the expression of a subset of genes at the level of pre-mRNA 3' end processing (O'Reilly et al., 2012). I have analysed the expression of vU1 snRNA genes throughout hES cell differentiation and shown that vU1 snRNA genes are down regulated upon differentiation into macrophages. Interestingly, analyses of steady state levels of specific vU1 snRNAs throughout hES cell differentiation revealed a characteristic pattern where specific vU1 snRNAs are more stable in the final differentiation step (i.e. macrophages). Thus, strongly supporting the idea that the vU1 snRNA genes are being regulated throughout differentiation both at the level of transcription and snRNA stability. Furthermore, vU1 snRNAs are up regulated upon reprogramming of primary human skin fibroblasts into induced pluripotent stem (iPS) cells, whose pattern of expression is similar to hES cells. Therefore, we hypothesize that vU1 snRNAs play a significant role in establishing pluripotent stem cells and that their differential expression may be key during development and cell reprogramming.</p

Factors controlling the pluripotent state of human embryonic stem cells

In the field of regenerative medicine, human embryonic stem (hES) cells offer the potential to treat degenerative diseases and replace damaged or non-functional tissue. However, it is not fully clear how hES cells retain a pluripotent state or differentiate into specific cell lineages. Although most of previous research has found that various proteins are responsible for the balance in hES cell maintenance and differentiation, there is mounting evidence for non-coding RNAs as important players in this task. Data from our laboratory shows that there are genes that encode for variants of the non-coding RNA U1 small nuclear (sn)RNA, a key component of the spliceosome. These variant (v)U1 snRNA genes are transcriptionally active and differentially expressed. Moreover, interfering with the activity of a specific vU1 snRNA affects the expression of a subset of genes at the level of pre-mRNA 3' end processing (O'Reilly et al., 2012). I have analysed the expression of vU1 snRNA genes throughout hES cell differentiation and shown that vU1 snRNA genes are down regulated upon differentiation into macrophages. Interestingly, analyses of steady state levels of specific vU1 snRNAs throughout hES cell differentiation revealed a characteristic pattern where specific vU1 snRNAs are more stable in the final differentiation step (i.e. macrophages). Thus, strongly supporting the idea that the vU1 snRNA genes are being regulated throughout differentiation both at the level of transcription and snRNA stability. Furthermore, vU1 snRNAs are up regulated upon reprogramming of primary human skin fibroblasts into induced pluripotent stem (iPS) cells, whose pattern of expression is similar to hES cells. Therefore, we hypothesize that vU1 snRNAs play a significant role in establishing pluripotent stem cells and that their differential expression may be key during development and cell reprogramming

Factors controlling the pluripotent state of human embryonic stem cells

In the field of regenerative medicine, human embryonic stem (hES) cells offer the potential to treat degenerative diseases and replace damaged or non-functional tissue. However, it is not fully clear how hES cells retain a pluripotent state or differentiate into specific cell lineages. Although most of previous research has found that various proteins are responsible for the balance in hES cell maintenance and differentiation, there is mounting evidence for non-coding RNAs as important players in this task. Data from our laboratory shows that there are genes that encode for variants of the non-coding RNA U1 small nuclear (sn)RNA, a key component of the spliceosome. These variant (v)U1 snRNA genes are transcriptionally active and differentially expressed. Moreover, interfering with the activity of a specific vU1 snRNA affects the expression of a subset of genes at the level of pre-mRNA 3' end processing (O'Reilly et al., 2012). I have analysed the expression of vU1 snRNA genes throughout hES cell differentiation and shown that vU1 snRNA genes are down regulated upon differentiation into macrophages. Interestingly, analyses of steady state levels of specific vU1 snRNAs throughout hES cell differentiation revealed a characteristic pattern where specific vU1 snRNAs are more stable in the final differentiation step (i.e. macrophages). Thus, strongly supporting the idea that the vU1 snRNA genes are being regulated throughout differentiation both at the level of transcription and snRNA stability. Furthermore, vU1 snRNAs are up regulated upon reprogramming of primary human skin fibroblasts into induced pluripotent stem (iPS) cells, whose pattern of expression is similar to hES cells. Therefore, we hypothesize that vU1 snRNAs play a significant role in establishing pluripotent stem cells and that their differential expression may be key during development and cell reprogramming.</p