Medical geography and its contribution to the aetiology of rare systemic connective tissue diseases : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in Geography at Massey University

This thesis is in two interrelated parts. Part One traced the historical development of medical geography since the idea of applying a geographical perspective to medical problems was first mooted in 4 B.C. The main trends in the evolving philosophy and methodology of this field were noted, and a distinction was made between the Western and Soviet interpretations of the nature and scope of medical geography. The methods available to medical geographers for cartographically portraying medical data were discussed. Part Two represented the application cf geographical principles to the study of rare systemic connective tissue diseases. The inherent problems of collection. and of verification of the medical data used in this study were detailed. Using cartographic and statistical techniques the diseases under study were spatially and temporally defined. It was found that scleroderma had a statistically significantly high incidence in the Taieri Geographic County, and it was this disease and this area which wore the principal contributory factors to the statistically significantly high incidence of all connective tissue diseases at the larger scales of areal units in the Otago region. The structures of the populations affected by these diseases were also studied, with the findings generally confirming the results obtained in overseas surveys. No association was found between the incidence of systemic lupus erythematosus, and high sunshine hours, while the disease subsets did not exhibit a rural or urban bias in their incidence. Paucity of cases precluded a study of the possible racial predilection of the diseases or any association of incidence with a patient's occupation. Suggested avenues for possible aetiological research accruing from this analysis were detailed

The Impact of Self-reported Visual Disability on Quality of Life among Older Persons in a Rural Area of Northeast Thailand: A Follow-up Study

A population-based cross-sectional study was conducted to follow-up an earlier study which estimated the prevalence of self-reported visual disability and its impact on the quality of life (QOL) of older persons living in a rural area of Northeast Thailand based on a secondary analysis of data collected for another purpose. Self-reported difficulty with seeing was used to determine prevalence of visual disability. The WHOQOL-BREF and WHOQOL-OLD were used to assess the impact of visual disability on QOL. Fifty nine percent reported having difficulty seeing to the extent that it interfered with their daily life. Those who reported having difficulty with seeing were found to be older, disproportionately female, have lower perception of health, and to score lower on QOL than those who did not. The findings of this study differed from the earlier study. It is asserted that the findings from this latter study are likely to be more representative of the situation due to the use of a more systematic and targeted sampling procedure

Does comorbidity explain the ethnic inequalities in cervical cancer survival in New Zealand? A retrospective cohort study

BACKGROUND: There are large ethnic differences in cervical cancer survival in New Zealand that are only partly explained by stage at diagnosis. We investigated the association of comorbidity with cervical cancer survival, and whether comorbidity accounted for the previously observed ethnic differences in survival. METHODS: The study involved 1,594 cervical cancer cases registered during 1994-2005. Comorbidity was measured using hospital events data and was classified using the Elixhauser instrument; effects on survival of individual comorbid conditions from the Elixhauser instrument were also assessed. Cox regression was used to estimate adjusted cervical cancer mortality hazard ratios (HRs). RESULTS: Comorbidity during the year before diagnosis was associated with cervical cancer-specific survival: those with an Elixhauser count of ≥3 (compared with a count of zero) had a HR of 2.17 (1.32-3.56). The HR per unit of Elixhauser count was 1.25 (1.11-1.40). However, adjustment for the Elixhauser instrument made no difference to the mortality HRs for Māori and Asian women (compared to 'Other' women), and made only a trivial difference to that for Pacific women. In contrast, concurrent adjustment for 12 individual comorbid conditions from the Elixhauser instrument reduced the Māori HR from 1.56 (1.19-2.05) to 1.44 (1.09-1.89), i.e. a reduction in the excess risk of 21%; and reduced the Pacific HR from 1.95 (1.21-3.13) to 1.62 (0.98-2.68), i.e. a reduction in the excess risk of 35%. CONCLUSIONS: Comorbidity is associated with cervical cancer-specific survival in New Zealand, but accounts for only a moderate proportion of the ethnic differences in survival

The Impact of Self-reported Visual Disability on Quality of Life among Older Persons in a Rural Area of Northeast Thailand: A Follow-up Study

A population-based cross-sectional study was conducted to follow-up an earlier study which estimated the prevalence of self-reported visual disability and its impact on the quality of life (QOL) of older persons living in a rural area of Northeast Thailand based on a secondary analysis of data collected for another purpose. Self-reported difficulty with seeing was used to determine prevalence of visual disability. The WHOQOL-BREF and WHOQOL-OLD were used to assess the impact of visual disability on QOL. Fifty nine percent reported having difficulty seeing to the extent that it interfered with their daily life. Those who reported having difficulty with seeing were found to be older, disproportionately female, have lower perception of health, and to score lower on QOL than those who did not. The findings of this study differed from the earlier study. It is asserted that the findings from this latter study are likely to be more representative of the situation due to the use of a more systematic and targeted sampling procedure

The Use of Flow-Injection Analysis with Chemiluminescence Detection of Aqueous Ferrous Iron in Waters Containing High Concentrations of Organic Compounds

An evaluation of flow-injection analysis with chemiluminescence detection (FIA-CL) to quantify Fe2+(aq) in freshwaters was performed. Iron-coordinating and/or iron-reducing compounds, dissolved organic matter (DOM), and samples from two natural water systems were used to amend standard solutions of Fe2+(aq). Slopes of the response curves from ferrous iron standards (1 – 100 nM) were compared to the response curves of iron standards containing the amendments. Results suggest that FIA-CL is not suitable for systems containing ascorbate, hydroxylamine, cysteine or DOM. Little or no change in sensitivity occurred in solutions of oxalate and glycine or in natural waters with little organic matter

Serum concentrations of chlorinated dibenzo-p-dioxins, furans and PCBs, among former phenoxy herbicide production workers and firefighters in New Zealand.

PURPOSE: To quantify serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds in former phenoxy herbicide production plant workers and firefighters, 20 years after 2,4,5-T production ceased. METHODS: Of 1025 workers employed any time during 1969-1984, 430 were randomly selected and invited to take part in a morbidity survey and provide a blood sample; 244 (57%) participated. Firefighters stationed in close proximity of the plant and/or engaged in call-outs to the plant between 1962 and 1987 also participated (39 of 70 invited). Reported here are the serum concentrations of TCDD and other chlorinated dibenzo-dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs). Determinants of the serum concentrations were assessed using linear regression. RESULTS: The 60 men who had worked in the phenoxy/TCP production area had a mean TCDD serum concentration of 19.1 pg/g lipid, three times the mean concentration of the 141 men and 43 women employed in other parts of the plant (6.3 and 6.0 pg/g respectively), and more than 10 times the mean for the firefighters (1.6 pg/g). Duration of employment in phenoxy herbicide synthesis, maintenance work, and work as a boilerman, chemist, and packer were associated with increased serum concentrations of TCDD and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD). Employment as a boilerman was also associated with elevated serum concentrations of PCBs. CONCLUSIONS: Occupations in the plant associated with phenoxy herbicide synthesis had elevated levels of TCDD and PeCDD. Most other people working within the plant, and the local firefighters, had serum concentrations of dioxin-like compounds comparable to those of the general population

Western Land Managers will Need all Available Tools for Adapting to Climate Change, Including Grazing: A Critique of Beschta et al.

In a previous article, Beschta et al. (Environ Manag 51(2):474–491, 2013) argue that grazing by large ungulates (both native and domestic) should be eliminated or greatly reduced on western public lands to reduce potential climate change impacts. The authors did not present a balanced synthesis of the scientific literature, and their publication is more of an opinion article. Their conclusions do not reflect the complexities associated with herbivore grazing. Because grazing is a complex ecological process, synthesis of the scientific literature can be a challenge. Legacy effects of uncontrolled grazing during the homestead era further complicate analysis of current grazing impacts. Interactions of climate change and grazing will depend on the specific situation. For example, increasing atmospheric CO₂ and temperatures may increase accumulation of fine fuels (primarily grasses) and thus increase wildfire risk. Prescribed grazing by livestock is one of the few management tools available for reducing fine fuel accumulation. While there are certainly points on the landscape where herbivore impacts can be identified, there are also vast grazed areas where impacts are minimal. Broad scale reduction of domestic and wild herbivores to help native plant communities cope with climate change will be unnecessary because over the past 20–50 years land managers have actively sought to bring populations of native and domestic herbivores in balance with the potential of vegetation and soils. To cope with a changing climate, land managers will need access to all available vegetation management tools, including grazing.Keywords: Grazing, Riparian areas, Public lands, Climate chang

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

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