Reliability of routinely collected hospital data for child maltreatment surveillance

Background: Internationally, research on child maltreatment-related injuries has been hampered by a lack of available routinely collected health data to identify cases, examine causes, identify risk factors and explore health outcomes. Routinely collected hospital separation data coded using the International Classification of Diseases and Related Health Problems (ICD) system provide an internationally standardised data source for classifying and aggregating diseases, injuries, causes of injuries and related health conditions for statistical purposes. However, there has been limited research to examine the reliability of these data for child maltreatment surveillance purposes. This study examined the reliability of coding of child maltreatment in Queensland, Australia. Methods: A retrospective medical record review and recoding methodology was used to assess the reliability of coding of child maltreatment. A stratified sample of hospitals across Queensland was selected for this study, and a stratified random sample of cases was selected from within those hospitals. Results: In 3.6% of cases the coders disagreed on whether any maltreatment code could be assigned (definite or possible) versus no maltreatment being assigned (unintentional injury), giving a sensitivity of 0.982 and specificity of 0.948. The review of these cases where discrepancies existed revealed that all cases had some indications of risk documented in the records. 15.5% of cases originally assigned a definite or possible maltreatment code, were recoded to a more or less definite strata. In terms of the number and type of maltreatment codes assigned, the auditor assigned a greater number of maltreatment types based on the medical documentation than the original coder assigned (22% of the auditor coded cases had more than one maltreatment type assigned compared to only 6% of the original coded data). The maltreatment types which were the most ‘under-coded’ by the original coder were psychological abuse and neglect. Cases coded with a sexual abuse code showed the highest level of reliability. Conclusion: Given the increasing international attention being given to improving the uniformity of reporting of child-maltreatment related injuries and the emphasis on the better utilisation of routinely collected health data, this study provides an estimate of the reliability of maltreatment-specific ICD-10-AM codes assigned in an inpatient setting.

Content and functionality of alcohol and other drug websites : results of an online survey

Background: There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood. ----- ----- Objective: To investigate content and functionality preferences for AOD and other health websites. Methods: An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences. ----- ----- Results: Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents. ----- ----- Conclusions: Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.

Online alcohol interventions : a systematic review

Background: There has been a significant increase in the availability of online programs for alcohol problems. A systematic review of the research evidence underpinning these programs is timely. Objectives: Our objective was to review the efficacy of online interventions for alcohol misuse. Systematic searches of Medline, PsycINFO, Web of Science, and Scopus were conducted for English abstracts (excluding dissertations) published from 1998 onward. Search terms were: (1) Internet, Web*; (2) online, computer*; (3) alcohol*; and (4) E\effect*, trial*, random* (where * denotes a wildcard). Forward and backward searches from identified papers were also conducted. Articles were included if (1) the primary intervention was delivered and accessed via the Internet, (2) the intervention focused on moderating or stopping alcohol consumption, and (3) the study was a randomized controlled trial of an alcohol-related screen, assessment, or intervention. Results: The literature search initially yielded 31 randomized controlled trials (RCTs), 17 of which met inclusion criteria. Of these 17 studies, 12 (70.6%) were conducted with university students, and 11 (64.7%) specifically focused on at-risk, heavy, or binge drinkers. Sample sizes ranged from 40 to 3216 (median 261), with 12 (70.6%) studies predominantly involving brief personalized feedback interventions. Using published data, effect sizes could be extracted from 8 of the 17 studies. In relation to alcohol units per week or month and based on 5 RCTs where a measure of alcohol units per week or month could be extracted, differential effect sizes to post treatment ranged from 0.02 to 0.81 (mean 0.42, median 0.54). Pre-post effect sizes for brief personalized feedback interventions ranged from 0.02 to 0.81, and in 2 multi-session modularized interventions, a pre-post effect size of 0.56 was obtained in both. Pre-post differential effect sizes for peak blood alcohol concentrations (BAC) ranged from 0.22 to 0.88, with a mean effect size of 0.66. Conclusions: The available evidence suggests that users can benefit from online alcohol interventions and that this approach could be particularly useful for groups less likely to access traditional alcohol-related services, such as women, young people, and at-risk users. However, caution should be exercised given the limited number of studies allowing extraction of effect sizes, the heterogeneity of outcome measures and follow-up periods, and the large proportion of student-based studies. More extensive RCTs in community samples are required to better understand the efficacy of specific online alcohol approaches, program dosage, the additive effect of telephone or face-to-face interventions, and effective strategies for their dissemination and marketing.

Low intensity CBT by mail

Introduction: There are many low intensity (LI) cognitive behavoural therapy (CBT) solutions to the problem of limited service access. In this chapter, we aim to discuss a relatively low-technology approach to access using standard postal services-CBT by mail, or M-CBT. Bibliotherapies including M-CBT teach key concepts and self-management techniques, together with screening tools and forms to structure home practice. M-CBT differs from other bibliotherapies by segmenting interventions and mailing them at regular intervals. Most involve participants returning copies of monitoring forms or completed handouts. Therapist feedback is provided, often in personal letters that accompany the printed materials. Participants may also be given access to telephone or email support. ----- ----- M-CBT clearly fulfills criteria for an LI CBT (see Bennett-Levy et al., Chapter 1, for a definition of LI interventions). Once written, they involve little therapist time and rely heavily on self-management. However, content and overall treatment duration need not be compromised. Long-term interventions with multiple components can be delivered via this method, provided their content can be communicated in letters and engagement is maintained.

Implementing low intensity CBT in case management of clients with severe mental illness

In a previous chapter (Dean and Kavanagh, Chapter 37), the authors made a case for applying low intensity (LI) cognitive behaviour therapy (CBT) to people with serious mental illness (SMI). As in other populations, LI CBT interventions typically deal with circumscribed problems or behaviours. LI CBT retains an emphasis on self-management, has restricted content and segment length, and does not necessarily require extensive CBT training. In applying these interventions to SMI, adjustments may be needed to address cognitive and symptomatic difficulties often faced by these groups. What may take a single session in a less affected population may require several sessions or a thematic application of the strategy within case management. In some cases, the LI CBT may begin to appear more like a high-intensity (HI) intervention, albeit simple and with many LI CBT characteristics still retained. So, if goal setting were introduced in one or two sessions, it could clearly be seen as an LI intervention. When applied to several different situations and across many sessions, it may be indistinguishable from a simple HI treatment, even if it retains the same format and is effectively applied by a practitioner with limited CBT training. ----- ----- In some ways, LI CBT should be well suited to case management of patients with SMI. treating staff typically have heavy workloads, and find it difficult to apply time-consuming treatments (Singh et al. 2003). LI CBT may allow provision of support to greater numbers of service users, and allow staff to spend more time on those who need intensive and sustained support. However, the introduction of any change in practice has to address significant challenges, and LI CBT is no exception. ----- ----- Many of the issues that we face in applying LI CBT to routine case management in a mnetal health service and their potential solutions are essentially the same as in a range of other problem domains (Turner and Sanders 2006)- and, indeed, are similar to those in any adoption of innovation (Rogers 2003). Over the last 20 years, several commentators have described barriers to implementing evidence-based innovations in mental health services (Corrigan et al. 1992; Deane et al. 2006; Kavanagh et al. 1993). The aim of the current chapter is to present a cognitive behavioural conceptualisation of problems and potential solutions for dissemination of LI CBT.

Adapting low intensity CBT interventions for clients with severe mental illness

Many people with severe mental illness (SMI) such as schizophrenia, whose psychotic symptoms are effectively managed, continue to experience significant functional problems. This chapter argues that low intensity (LI) cognitive behaviour therapy (CBT; e.g. for depression, anxiety, or other issues) is applicable to these clients, and that LI CBT can be consistent with long-term case management. However, adjustments to LI CBT strategies are often necessary and boundaries between LI CBT and high intensity (HI) CBT (with more extensive practitioner contact and complexity) may become blurred. Our focus is on LI CBT's self-management emphasis, its restricted content and segment length, and potential use after limited training. In addition to exploring these issues, it draws on the authors' Collaborative Recovery (CR; Oades et al. 2005) and 'Start Over and Survive' programs (Kavanagh et al. 2004) as examples. ----- ----- Evidence for the effectiveness of LI CBT with severe mental illness is often embedded within multicomponent programs. For example, goal setting and therapeutic homework are common components of such programs, but they can also be used as discrete LI CBT interventions. A review of 40 randomised controlled trials involving recipients with schizophrenia or other sever mental illnesses has identified key components of illness management programs (Mueser et al. 2002). However, it is relatively rare for specific components of these complex interventions to be assessed in isolation. Given these constraints, the evidence for specific LI CBT interventions with severe mental ilnness is relatively limited.

Brief motivational interviewing for depression and anxiety

Motivational interviewing (MI)can be applied as a brief, low intensity (LI) intervention of 1-4 individualised sessions (typically 45-60 minutes in duration), including screening, assessment feedback, and psycho-education. MI is a client-centred, directive therapeutic style that enhances readiness for change by helping clients explore and resolve ambivalence (Miller and Rollnick 2002). A summary of the key components of brief MI interventions is provided in Table 16.1. There is a well-established evidence base for MI in the treatment of substance misuse (particularly alcohol misuse; Moyer et al. 2002), as well as a growing evidence for the use of MI in the treatment of other mental disorders (e.g. depression, PTSD, OCD), as well as suicidality and physical health problems (Hettema et al. 2005). Brief MI intervention can be delivered as a standalone treatment or as a motivational prelude to pharmacological and/or other psychological treatments (Hettema et al. 2005). MI has been used as an accompaniment to cognitive behavioural therapy (CBT) in the treatment of both depression and anxiety for resolving ambivalence about change and developing strategies for responding to resistance (e.g. treatment attendance, homework/medication compliance; Arkowitz et al. 2008a, 2008b). This chapter will describe how to apply brief MI interventions to the treatment of depression and anxiety as applied to the case of Megan (see Box 16.1) along with some of the challenges and potential solutions to applying MI in practice.

Modular transactional memory

Software transactional memory has the potential to greatly simplify development of concurrent software, by supporting safe composition of concurrent shared-state abstractions. However, STM semantics are defined in terms of low-level reads and writes on individual memory locations, so implementations are unable to take advantage of the properties of user-defined abstractions. Consequently, the performance of transactions over some structures can be disappointing. ----- ----- We present Modular Transactional Memory, our framework which allows programmers to extend STM with concurrency control algorithms tailored to the data structures they use in concurrent programs. We describe our implementation in Concurrent Haskell, and two example structures: a finite map which allows concurrent transactions to operate on disjoint sets of keys, and a non-deterministic channel which supports concurrent sources and sinks. ----- ----- Our approach is based on previous work by others on boosted and open-nested transactions, with one significant development: transactions are given types which denote the concurrency control algorithms they employ. Typed transactions offer a higher level of assurance for programmers reusing transactional code, and allow more flexible abstract concurrency control.

Non-pharmacological interventions in secondary schizophrenia

Schizophrenia may not be a single disease, but the result of a diverse set of related conditions. Modern neuroscience is beginning to reveal some of the genetic and environmental underpinnings of schizophrenia; however, an approach less well travelled is to examine the medical disorders that produce symptoms resembling schizophrenia. This book is the first major attempt to bring together the diseases that produce what has been termed 'secondary schizophrenia'. International experts from diverse backgrounds ask the questions: does this medical disorder, or drug, or condition cause psychosis? If yes, does it resemble schizophrenia? What mechanisms form the basis of this relationship? What implications does this understanding have for aetiology and treatment? The answers are a feast for clinicians and researchers of psychosis and schizophrenia. They mark the next step in trying to meet the most important challenge to modern neuroscience – understanding and conquering this most mysterious of human diseases.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).

Involvement of Exo1b in DNA damage-induced apoptosis

Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair.

Chlamydia pneumoniae is genetically diverse in animals and appears to have crossed the host barrier to humans on (at least) two occasions

Chlamydia pneumoniae is a common human and animal pathogen associated with a wide range of diseases. Since the first isolation of C. pneumoniae TWAR in 1965, all human isolates have been essentially clonal, providing little evolutionary insight. To address this gap, we investigated the genetic diversity of 30 isolates from diverse geographical locations, from both human and animal origin (amphibian, reptilian, equine and marsupial). Based on the level of variation that we observed at 23 discreet gene loci, it was clearly evident that the animal isolates were more diverse than the isolates of human origin. Furthermore, we show that C. pneumoniae isolates could be grouped into five major genotypes, A-E, with A, B, D and E genotypes linked by geographical location, whereas genotype C was found across multiple continents. Our evidence strongly supports two separate animal-to-human cross species transfer events in the evolutionary history of this pathogen. The C. pneumoniae human genotype identified in the USA, Canada, Taiwan, Iran, Japan, Korea and Australia (non- Indigenous) most likely originated from a single amphibian or reptilian lineage, which appears to have been previously geographically widespread. We identified a separate human lineage present in two Australian Indigenous isolates (independent geographical locations). This lineage is distinct and is present in Australian amphibians as well as a range of Australian marsupials.

Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks

DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability.