Operating during the COVID-19 pandemic: How to reduce medical error.

Our professional and private lives changed on March 11 2020 when the coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO. By March 16, surgical training was suspended, MRCS and FRCS examinations cancelled and all courses postponed. In theory, essential cancer surgery, emergency and trauma operating will continue. All elective, non-essential cases are currently cancelled. While we adapt to our new ways of working, we remind ourselves that surgeons are flexible, resilient and, ultimately, we are doctors in the first instance. We present a short article on operating during the COVID-19 pandemic.

Reducing medical error during a pandemic.

On 30 January 2020, the WHO declared the coronavirus disease 2019 (COVID-19) a public health emergency of international concern. By 11 March 2020, it was designated a pandemic owing to its rapid worldwide spread. In this short article we provide some information that might be useful and help equip colleagues to reduce medical error during a pandemic. We advocate a systems-based approach, rather than an individual's sole responsibility, and, look at ways to provide safer healthcare.

The impact of the Major Trauma Network: will trauma units continue to treat complex foot and ankle injuries?

INTRODUCTION: April 1st 2012 saw the introduction of National Trauma Networks in England. The aim to optimise the management of major trauma. Patients with an ISS≥16 would be transferred to the regional Major Trauma Centre (level 1). Our premise was that trauma units (level 2) would no longer manage complex foot and ankle injuries thereby obviating the need for a foot and ankle specialist service. METHODS: Retrospective analysis of the epidemiology of foot and ankle injuries, using the Gloucestershire trauma database, from a trauma unit with a population of 750,000. Rates of open fractures, complex foot and ankle injuries and requirement for stabilisation with external fixation were reviewed before and after the introduction of the regional Trauma Network. Secondly, using the Trauma Audit & Research Network (TARN) database, all foot and ankle injuries triaged to the regional Major Trauma Centre (MTC) were reviewed. RESULTS: Incidence of open foot and ankle injuries was 2.9 per 100,000 per year. There were 5.1% open injuries before the network and 3.2% after (p>0.05). Frequency of complex foot and ankle injuries was 4.2% before and 7.5% after the network commenced, showing no significant change. There was no statistically significant change in the numbers of patients with complex foot and ankle injuries treated by application of external fixators. Analysis of TARN data revealed that only 18% of patients with foot and ankle injuries taken to the MTC had an ISS≥16. The majority of these patients were identified as requiring plastic surgical intervention for open fractures (69%) or were polytrauma patients (43%). Only 4.5% of patients had isolated, closed foot and ankle injuries. CONCLUSION: We found that at the trauma unit there was no decrease in the numbers of complex foot and ankle injuries, open fractures, or the applications of external fixators, following the introduction of the Trauma Network. These patients will continue to attend trauma units as they usually have an ISS<16. Our findings suggest that there is still a need for foot and ankle specialists at trauma units, in order to manage patients with complex foot and ankle injuries.

Comorbid ADHD and mental health disorders: are these children more likely to develop reading disorders?

While attention-deficit/hyperactivity disorder (ADHD) has been associated with both internalizing and externalizing childhood behaviour disorders, the specific relationship of these comorbid disorders to ADHD and reading problems is less well defined. The present study analysed data from the Australian Twin ADHD Project, which utilized DSM-IV-based ratings of ADHD, separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, and oppositional defiant disorder for twins and siblings aged 6 to 18 years. While differences between children with and without ADHD were demonstrated for those with separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, oppositional defiant disorder and a reading disorder, for all age groups, regression analysis of ADHD diagnostic subtypes by age and reading disorder showed that only generalized anxiety disorder remained significant after controlling for ADHD subtypes. Analysis of the mean reading disorder scores in children with and without ADHD showed that children with conduct disorder had significantly more reading problems, as did children with multiple comorbid disorders. In summary, both age and ADHD diagnosis were associated with variations in these comorbid disorders, and multiple comorbid disorders were associated with greater reading impairment.

Attention deficit hyperactivity disorder: a Rasch analysis of the SWAN Rating Scale.

The prevalence of attention-deficit/hyperactivity disorder (ADHD) has been estimated at 3-7% in the population. Children with this disorder are often characterized by symptoms of inattention and/or impulsivity and hyperactivity, which can significantly impact on many aspects of their behaviour and performance. This study investigated the characteristics of the SWAN Rating Scale and its discrimination of ADHD subtypes. This instrument was developed by Swanson and his colleagues and measures attentiveness and hyperactivity on a continuum, from attention problems to positive attention skills, using a seven-point scale of behaviour: "far below average" to "far above average". The Australian Twin Attention-Deficit/Hyperactivity Disorder Study consists of questionnaire data collected from families in 1990/2007. The Rasch model was used to measure the characteristics of items from the SWAN Rating Scale; how well these items discriminated between those with and without ADHD. The prevalence of each subtype was found to be 5.3% for inattentive ADHD, 4.3% for hyperactive ADHD and 4.6% for combined ADHD. A total of 14.2% of the cohort appeared to have ADHD. While the inattentive items appeared to be consistent with each other in their measurement behaviour and response patterns, the hyperactive items were less consistent. Further, the combined subtype appeared to be an entirely different type, with unique features unlike the other two subtypes. Further work is needed to distinguish the diagnostic features of each subtype of ADHD.

Simple identification of complex ADHD subtypes using current symptom counts.

OBJECTIVE: New attention-deficit/hyperactivity disorder (ADHD) subtypes identified through latent class analysis have been recently proposed. Here, we assess the accuracy of simple rules based on symptom counts for the assignment of youths to clinically relevant population-derived ADHD subtypes: severe inattentive (SI) and severe combined (SC). METHOD: Data from 9,675 twins and siblings from Missouri and Australia aged 7 to 19 years were analyzed using continuous and categorical models of ADHD symptoms using principal components analysis and subtyping by DSM-IV and by latent class criteria. Cut points were derived for classifying SI and SC subtypes by positive predictive value, negative predictive value, percent positive agreement, and Matthew coefficient of agreement. RESULTS: Principal components analysis suggested two underlying factors: total number of symptoms and symptom type, with SI and SC latent class subtypes clearly mapping to distinct areas on a plot of these factors. Having six or more total symptoms and fewer than three hyperactive-impulsive symptoms accurately predicts the latent class SI subtype. The latent class SC subtype was best identified by 11 or more total symptoms and 4 or more hyperactive-impulsive. The DSM-IV ADHD subtype criteria accurately identified the SC subtype but only poorly for the SI subtype. CONCLUSIONS: Symptom counts criteria allow the simple and accurate identification of subjects with severe ADHD subtypes defined by latent class analysis. Such simple symptom counts corresponding to screening cut points selected latent class-derived SI subtype subjects with greater precision than DSM-IV criteria.

Genetic influences on handedness: data from 25,732 Australian and Dutch twin families.

Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.

What are the key directions in the genetics of attention deficit hyperactivity disorder?

PURPOSE OF REVIEW: The aim of this review is to describe the considerable advances in consolidating the empirical evidence on several key topics in the genetics of attention deficit hyperactivity disorder, namely the quantitative genetic studies of the nature of attention deficit hyperactivity disorder and its comorbidities, the molecular genetic studies that show modest but consistent effects of specific genotypes, and the growing recognition of genotype by environment interaction. Such interactions are studied to explain what happens when individuals with a susceptible genotype are exposed to a particular environment. RECENT FINDINGS: There have been a significant number of twin studies that have examined different models of the symptomatology of attention deficit hyperactivity disorder and how these symptoms are reported. Similarly, molecular genetic research is complicated by very different outcome measures, and study across the whole field is made more problematic by genotype by environment interaction effects. One of the most interesting areas of development is that of psychopharmacogenetics. SUMMARY: Two key developments have been integrative models of the genetics of attention deficit hyperactivity disorder and brain structure, which may have implications for future attention deficit hyperactivity disorder subtyping, and collaboration. This is not just within attention deficit hyperactivity disorder as in the IMAGE study, but also across disciplines.

Fragile X--a challenge to models of the mind and to best clinical practice.

Cornish et al. (2008, this issue) provide an excellent review of Fragile X a common but very complex cause of intellectual disability. They report on a cohort of such males of normal intelligence quotient (IQ) and socioeconomic status (SES), but who have deficits in selective attention and growing impairment in response inhibition. This paper has theoretical views for our models of the mind and clinical implications for families where Fragile X may never have been considered as a possible cause of some of the problems in male and female family members and possibly as well for other disorders such as attention deficit hyperactivity disorder (ADHD) and autism.

Depressive symptomatology in child and adolescent twins with attention-deficit hyperactivity disorder and/or developmental coordination disorder.

Previous research has demonstrated a link between attention-deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD), and depression. The present study utilized a monozygotic (MZ) differences design to investigate differences in depressive symptomatology between MZ twins discordant for ADHD or DCD. This extends previous research as it controls for genetic effects and shared environmental influences and enables the investigation of nonshared environmental influences. In addition, children and adolescents with comorbid ADHD and DCD were compared on their level of depressive symptomatology to those with ADHD only, DCD only, and no ADHD or DCD. The parent-rated Strengths and Weaknesses of ADHD Symptoms and Normal Behavior, Developmental Coordination Disorder Questionnaire, and Sad Affect Scale were used to assess ADHD, DCD, and depressive symptomatology respectively. The results revealed higher levels of depressive symptomatology in MZ twins with ADHD or DCD compared to their nonaffected co-twins. In addition, children and adolescents with comorbid ADHD and DCD demonstrated higher levels of depressive symptomatology compared to those with ADHD only, DCD only, and no ADHD or DCD. The implications of these findings are discussed with emphasis on understanding and recognizing the relationship between ADHD, DCD, and depression in the assessment and intervention for children and adolescents with these disorders.

A twin study of attention-deficit/hyperactivity disorder dimensions rated by the strengths and weaknesses of ADHD-symptoms and normal-behavior (SWAN) scale.

BACKGROUND: When symptom rating scales are used in the general population, there is severe skewness, with many individuals having no symptoms. While this has major implications for genetic designs that require extremely discordant and concordant (EDAC) siblings, little is known of the genetics of scales which seek to differentiate within the "no ADHD symptom" group. METHODS: Parents of Australian twins completed two attention-deficit/hyperactivity disorder (ADHD) questionnaires, the Australian Twin Behaviour Rating Scale (ATBRS), based on conventional DSM-IV symptom scores, and the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behavior (SWAN) scale, which includes above-average performance on attention and activity. The two scales were compared in two age groups of same-sex twins, 528 pairs aged 6 to 9 and 488 pairs aged 12 to 20. RESULTS: Parents reported higher levels of activity and attention in their twins when reporting using the SWAN scale than when using the ATBRS, and while the monozygotic (MZ) correlations were similar on both scales, the dizygotic (DZ) correlations were consistently higher on the SWAN. On DSM-IV based scales, parents exaggerated differences within those sibling pairs in the "with few ADHD symptoms" category. CONCLUSIONS: The SWAN may provide a more realistic description of the ADHD phenotype for the selection of twin and sibling pairs for genetic analysis.

Meeting the educational needs of multiple birth children.

There has been a significant increase in the number of twins and higher multiples so that one child in 33 is now a multiple. It is therefore not unusual for schools to have several sets of twins, as well as triplets and even higher multiples. By being the same age and in the same school year if not class, twins and higher multiples are not like brothers and sisters born closely together. Teachers and parents need to be aware of particular issues that may affect the physical, intellectual, personal, social and emotional development of multiple birth children, and to ensure that school policy and practice include this special group of children and parents. These issues include: preterm birth catch-up and implications for starting school; the balance of competition and cooperation among multiples; separation in school and the evidence from recent longitudinal studies; legislative and other initiatives on the development of school policy; the particular needs of higher multiples.

Having a co-twin with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder which occurs more often in twins than singletons. This article focuses on the psychosocial consequences of having a co-twin with ADHD. Specifically, the level of anxiety (generalized and separation) in non-ADHD children who have a co-twin with ADHD is examined using data from the Australian Twin ADHD Project (ATAP). Parental report data on 501 dizygotic (DZ) twin pairs aged 6 to 15 and their siblings were used to examine (i) anxiety symptoms in twin pairs discordant for ADHD, (ii) how the effects of an ADHD twin on their co-twin and siblings are related to the type of ADHD, and (iii) whether the effects are greater for the nonaffected twin than nontwin siblings. Results show that anxiety was high in co-twins of children with the combined subtype of ADHD, with increased symptoms of both generalized and separation anxiety. Inattentive ADHD had smaller effects, which were confined to generalized anxiety and were specific to the co-twin rather than other siblings. These results have clinical implications in managing the entire multiple birth family where one twin has ADHD, and also has implications for genetic analysis in modeling the relationship of ADHD to internalizing disorders.

The Australian Twin ADHD Project: current status and future directions.

This article describes the Australian Twin Attention-deficit/hyperactivity disorder (ADHD) Project (ATAP), the results of research conducted using this database and plans for future studies. Information has been actively collected from Australian families with twin children since 1991 for the ATAP database. The value of assessing siblings as well as twins is emphasized. Much work has gone into continuing the involvement of families in the study though this does become more difficult when twins reach maturity. The main focus of the project is ADHD in children and adolescents plus comorbid conditions including conduct disorder, oppositional defiant disorder, and generalized anxiety disorder. A major challenge has been how to retain continuity in the assessments, while at the same time covering changes in psychiatric classification, such as the move to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). Changes in the scale can affect the reports of twin similarity. Over the years, these twins have become part of other twin studies and future plans include linking different twin databases to investigate the relationships between childhood behavior and adult conditions. Recruitment, assessment and retention of twin families require a major commitment but create a significant resource for collaboration in areas outside the original aim.

Cryptophycins-309, 249 and other cryptophycin analogs: preclinical efficacy studies with mouse and human tumors.

Cryptophycins-1 and 52 (epoxides) were discovered to have in-vitro and in-vivo antitumor activity in the early 1990s. The chlorohydrins of these, Cryptophycins-8 and 55 (also discovered in the early 1990s) were markedly more active, but could not be formulated as stable solutions. With no method to adequately stabilize the chlorohydrins at the time, Cryptophycin-52 (LY 355073) entered clinical trials, producing only marginal antitumor activity. Since that time, glycinate esters of the hydroxyl group of the chlorohydrins have been synthesized and found to provide stability. Three of the most active were compared herein. Cryptophycin-309 (C-309) is a glycinate ester of the chlorohydrin Cryptophycin-296. The glycinate derivative provided both chemical stability and improved aqueous solubility. After the examination of 81 different Cryptophycin analogs in tumor bearing animals, C-309 has emerged as superior to all others. The following %T/C and Log Kill (LK) values were obtained from a single course of IV treatment (Q2d x 5) against early staged SC transplantable tumors of mouse and human origin: Mam 17/Adr [a pgp (+) MDR tumor]: 0%T/C, 3.2 LK; Mam 16/C/Adr [a pgp (-) MDR tumor]: 0%T/C, 3.3 LK; Mam 16/C: 0%T/C, 3.8 LK; Colon 26: 0%T/C, 2.2 LK; Colon 51: 0%T/C, 2.4 LK; Pancreatic Ductal Adenocarcinoma 02 (Panc 02): 0%T/C, 2.4 LK; Human Colon HCT15 [a pgp (+) MDR tumor]: 0%T/C, 3.3 LK; Human Colon HCT116: 0%T/C, 4.1 LK. One additional analog, Cryptophycin-249 (C-249, the glycinate of Cryptophycin-8), also emerged with efficacy rivaling or superior to C-309. However, there was sufficient material for only a single C-249 trial in which a 4.0 LK was obtained against the multidrug resistant breast adenocarcinoma Mam-16/C/Adr. C-309 and C-249 are being considered as second-generation clinical candidates.

Gender differences in ADHD subtype comorbidity.

OBJECTIVE: To examine gender differences in attention-deficit/hyperactivity disorder ("ADHD") symptom comorbidity with "oppositional defiant disorder", "conduct disorder", "separation anxiety disorder", "generalized anxiety disorder", speech therapy, and remedial reading in children. METHOD: From 1994 to 1995, data from a large sample (N = 4,371) of twins and siblings studied in the Australian Twin ADHD Project were obtained by mailed DSM-IV-based questionnaires, investigating patterns of comorbidity in the three subtypes of "ADHD": "inattentive", "hyperactive/impulsive", and "combined". A total of 1,550 questionnaires were returned (87%) over the next 12 to 18 months. RESULTS: Analysis of variance showed significant between-group differences in males and females for inattention and hyperactive/impulsive symptom counts with higher rates of "oppositional defiant disorder" and "conduct disorder" in males, and higher rates of "separation anxiety disorder" in females indicating internalizing disorders are more common in females and externalizing disorders are occurring more often in males. Differences were found between the "ADHD" subtypes and the no ADHD category for all comorbid conditions, for both males and females. Children without ADHD consistently had fewer symptoms, while children with the combined subtype showed consistently more comorbid symptoms indicating a strong relationship between high rates of externalizing symptoms and high rates of internalizing symptoms. Gender differences in speech therapy were significant only for the children without ADHD. The rates of "separation anxiety disorder" were higher in females with the "inattention" subtype and the rate of "generalized anxiety disorder" higher for females with the "combined" subtype, indicating that the subtypes of ADHD were associated with these internalizing disorders in different ways. CONCLUSIONS: Although comorbidity differs among ADHD subtypes, there were no significant gender differences in comorbidity for externalizing disorders. Inattentive girls may present with anxiety. Clinical approaches for both males and females should be sensitive to possible language and reading problems.