WHO long form scoring, reliability, validity and norms for New Zealand : a thesis presented in fulfilment of the requirements for the degree of Master of Public Health at Massey University, Wellington Campus, New Zealand

Background Self-reported health measures provide information about a wider range of health outcomes than objective measures of health status, such as mortality and hospitalisation rates. National health surveys play a role in monitoring population health. The New Zealand Health Monitor (NZHM) is the organised, co-ordinated and integrated survey programme of the Ministry of Health in New Zealand. The New Zealand Health Survey (NZHS) is one of the chief surveys of the NZHM. One of the categories of information collected in the NZHM is health outcomes, and within this there is the subcategory of health status. The International Classification of Functioning and Disability (ICF) provides the framework to describe the critical elements of non-fatal health outcomes captured by health status instruments. NZHM is to collect data on most if not all of these 21 ICF dimensions. The WHO Long Form was developed as the health module in the WHO Multi-country Survey Study. The WHO Long Form is made up of 20 health domains, some overlapping with the eight SF-36 domains. The WHO Long Form did not have a set scoring system for scales, unlike the SF-36 instrument. The SF-36 has been previously tested and validated in New Zealand in the 1996/97 NZHS. Methods The 2002/03 NZHS used a complex sample design. A total of 12,929 people responded to the survey, with 12,529 respondents being included in the CURF dataset available for research. The health status section of the 2002/03 NZHS measures health-related quality of life (HRQL) covered 16 health and health-related domains. The questions were derived from the SF-36 and the WHO Long Form questionnaire on health status. The health domains covered in the 2002/03 NZHS were general health, vision, hearing, digestion, breathing, pain, sleep, energy and vitality, understanding, communication, physical functioning, self-care. The health-related domains covered in the 2002/03 NZHS were mental health, role-physical and role-emotional (usual activities), and social functioning. There were five key aims specific to the current thesis. First, to group the WHO Long Form items in the 2002/03 NZHS into scales for each health domain and develop standard scoring protocols for each scale. Second, to test the reliability of the scales using standard psychometric tests for the total NZ population and for major population subgroups. Third, to test the validity of the scales using the standard psychometric tests for the total NZ population and for major population subgroups. Fourth, to construct norms for the WHO Long Form scales for the NZ population. And finally, to provide recommendations for the health status component of future NZ health surveys. Results In summary, this thesis developed a method for producing scale scores for domains of health not previously measured in New Zealand Health Surveys, providing greater coverage of domains from the ICF. There were virtually no missing data for all items and subgroups within the questions used to develop the scales. The scaling approach was consistent with that for the SF-36, allowing the new scales to be presented alongside the SF-36 scales. All scales for the total population and major population subgroups met the required criterion for satisfactory psychometric properties, with the exception of digestion and bodily excretions scale. For the digestion and bodily excretions scale, the Cronbach's alpha was lower than that required for between group comparisons. The composite physical functioning and social functioning scales performed no better than the existing SF-36 scales and were highly correlated with these scales. Conclusion Notwithstanding the limitations of this study, key findings of interest are that the new WHO Long Form questions can be used to form scales that cover physical functioning, social functioning, vision, hearing, digestion and bodily excretions, breathing, self-care, understanding, communication and sleep. The majority of the questions and scales work for the NZ population and subgroups. All but one of the scales, digestion and bodily excretions, have satisfactory psychometric properties for the total population and major subpopulation groups of interest. The respondent burden is an important consideration for the NZHS, thus it cannot be argued that enough is gained from adding questions to the physical functioning and Social Functioning domains, thus it would be recommended that the SF-36 scales are used to measure there two domains of health. The new WHO Long Form scales can now be presented alongside the SF-36 scales and used in future analyses looking at interrelationships between factors such as health risk and health status

Disability and disability services

This chapter provides a profile of people who are at various points on this disability continuum, but with an emphasis on those facing more severe limitations. Information is presented on both mainstream and sector-specific service use, and the outcomes associated with the use of these services. The focus in this chapter is on people aged under 65 years.<br /

Detection and metabolic investigations of a novel designer steroid: 3-chloro-17α-methyl-5α-androstan-17β-ol

In 2012, seized capsules containing white powder were analyzed to show the presence of unknown steroid-related compounds. Subsequent gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) investigations identified a mixture of 3α- and 3β- isomers of the novel compound; 3-chloro-17α-methyl-α-androstan-17β-ol. Synthesis of authentic reference materials followed by comparison of NMR, GC-MS and gas chromatography-tandem mass spectrometry (GC-MS/MS) data confirmed the finding of a new ‘designer’ steroid. Furthermore, in vitro androgen bioassays showed potent activity highlighting the potential for doping using this steroid. Due to the potential toxicity of the halogenated steroid, in vitro metabolic investigations of 3α-chloro-17α-methyl-α-androstan-17β-ol using equine and human S9 liver fractions were performed. For equine, GC-MS/MS analysis identified the diagnostic 3α-chloro-17α-methyl-5α-androstane-16α,17β-diol metabolite. For human, the 17α-methyl-α-androstane-3α,17β-diol metabolite was found. Results from these studies were used to verify the ability of GC-MS/MS precursor-ion scanning techniques to support untargeted detection strategies for designer steroids in anti-doping analyses.Synthesis and in vitro metabolic investigations of 3α/β-chloro-17α-methyl-5α-androstan -17β-ol was suppo rted by the Austr a-lian Research Council Linkage Grant (LP120200444) Strat egies for the detection of designer ster oids in ra cehorses

A Critical Review of the Impact of Individual Placement Support for Enabling People with Severe and Enduring Mental Illness into Employment

Background: Employment is recognised as a vital health outcome for people with mental illness (MHTF 2016). Over 132,000 people with disabilities are supported into work through specialist employment schemes (DWP 2016). People with severe and enduring mental illness [SMI] have the highest unemployment rate and experience complex barriers and reduced opportunities to access work (Ravello 2014). Independent Placement Support [IPS] combines employment and mental health services to provide an effective approach for supporting people into employment (Centre for Mental Health, 2014). There is a paucity of evidence within the UK around the implementation and impact of IPS as an approach to enable people SMI to access work. Significance to Practice: The principles of IPS need to be set within a national employment pathway for consistency in supporting individuals with SMI into work. IPS training for employment support workers is key to increasing an understanding of mental health illness, addressing complex barriers and attitudes regarding an individual’s work capability. Promoting recovery and optimising an individual’s true potential in occupational skill and work capacity needs to be the key focus of intervention (Council for Work and Health 2016). Integrated employment and mental health services are required to improve client centred practice and inter-agency working. Collaborative working would increase employment opportunities and positive outcomes for individuals with SMI (Wilson and Cronin-Davis 2016). Occupational therapists can improve vocational outcomes for individuals by evaluating meaningful occupations that fit the person’s work roles, occupational skill and work capabilities to meet task demands (COT 2008). Occupational therapists are well placed in supporting individual’s with SMI into mainstream employment. Inclusion of occupational therapists within employment teams is essential for optimising opportunities for work

Congenital hypothyroidism: Space-time clustering of thyroid dysgenesis indicates a role for environmental factors in disease etiology

Background: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis (DG) is unknown. If transient environmental factors can impact on thyroid gland development, then clustering of cases in time and/or space may occur, and this would be more likely in thyroid DG than dyshormonogenesis (DHG). Methods: The newborn screening program for CHT in Scotland is linked to a central database that includes case details such as postcode. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space–time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland between 1979 and 2015. We also looked for evidence of overall changes associated with sex and area-based birth density. Results: Of 531 cases with CHT during the study period, 290 cases had been categorized as DG (n = 229) or DHG (n = 61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology, but there was no seasonality. There was no evidence of overall space–time clustering (p = 0.06), but there was evidence of clustering in babies with DG (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space–time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p &lt; 0.001). Clustering of these cases was restricted to females but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of DHG. Conclusions: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid DG in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors

Meeting Report: Validation of Toxicogenomics-Based Test Systems: ECVAM–ICCVAM/NICEATM Considerations for Regulatory Use

This is the report of the first workshop “Validation of Toxicogenomics-Based Test Systems” held 11–12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was for participants to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicologic test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technologic experts, regulators, and the principal validation bodies and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would be a basis for the future validation of the technology when it reaches the appropriate stage. Because of the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas include a) biologic validation of toxicogenomics-based test methods for regulatory decision making, b) technical and bioinformatics aspects related to validation, and c) validation issues as they relate to regulatory acceptance and use of toxicogenomics-based test methods. In this report we summarize the discussions and describe in detail the recommendations for future direction and priorities

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research