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A CASE-CONTROL STUDY OF AMBIENT HEAT EXPOSURE AND UROLITHIASIS AMONG OUTDOOR WORKERS IN A SHIPBUILDING COMPANY, GUANGZHOU, CHINA Haiming Luo Bachelor of Medicine, Master of Science in Public Health Submitted in fulfilment of the requirements for the degree of Master of Applied Science (Research) School of Public Health and Social Work Queensland University of Technology July 2012

AMBIENT HEAT EXPOSURE AND UROLITHIASIS AMONG

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A CASE-CONTROL STUDY OF AMBIENT HEAT

EXPOSURE AND UROLITHIASIS AMONG OUTDOOR

WORKERS IN A SHIPBUILDING COMPANY,

GUANGZHOU, CHINA

Haiming Luo

Bachelor of Medicine, Master of Science in Public Health

Submitted in fulfilment of the requirements for the degree of

Master of Applied Science (Research)

School of Public Health and Social Work

Queensland University of Technology

July 2012

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KEY WORDS

Ambient heat exposure, Case-control study, Conditional logistic regression,

Guangzhou, Outdoor worker, Urolithiasis

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ABSTRACT

Higher ambient temperatures will increase heat stress on workers, leading to impacts

upon their individual health and productivity. In particular, research has indicated that

higher ambient temperatures can increase the prevalence of urolithiasis. This thesis

examines the relationship between ambient heat exposure and urolithiasis among

outdoor workers in a shipbuilding company in Guangzhou, China, and makes

recommendations for minimising the possible impacts of high ambient temperatures

on urolithiasis.

A retrospective 1:4 matched case-control study was performed to investigate the

association between ambient heat exposure and urolithiasis. Ambient heat exposure

was characterised by total exposure time, type of work, department and length of

service. The data were obtained from the affiliated hospital of the shipbuilding

company under study for the period 2003 to 2010. A conditional logistic regression

model was used to estimate the association between heat exposure and urolithiasis.

This study found that the odds ratio (OR) of urolithiasis for total exposure time was

1.5 (95% confidence interval (CI): 1.2–1.8). Eight types of work in the shipbuilding

company were investigated, including welder, assembler, production security and

quality inspector, planing machine operator, spray painter, gas-cutting worker and

indoor employee. Five out of eight types of work had significantly higher risks for

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urolithiasis, and four of the five mainly consisted of outdoors work with ORs of 4.4

(95% CI: 1.7–11.4) for spray painter, 3.8 (95% CI: 1.9–7.2) for welder, 2.7 (95% CI:

1.4–5.0) for production security and quality inspector, and 2.2 (95% CI: 1.1–4.3) for

assembler, compared to the reference group (indoor employee). Workers with

abnormal blood pressure (hypertension) were more likely to have urolithiasis with an

OR of 1.6 (95% CI: 1.0–2.5) compared to those without hypertension.

This study contributes to the understanding of the association between ambient heat

exposure and urolithiasis among outdoor workers in China. In the context of global

climate change, this is particularly important because rising temperatures are expected

to increase the prevalence of urolithiasis among outdoor workers, putting greater

pressure on productivity, occupational health management and health care systems.

The results of this study have clear implications for public health policy and planning,

as they indicate that more attention is required to protect outdoor workers from heat-

related urolithiasis.

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TABLE OF CONTENTS

KEY WORDS ................................................................................................................ I

ABSTRACT ................................................................................................................. III

LIST OF TABLES ....................................................................................................... IX

LIST OF FIGURES ...................................................................................................... X

LIST OF ABBREVIATIONS ...................................................................................... XI

STATEMENT OF AUTHORSHIP ........................................................................... XII

ACKNOWLEDGEMENTS ...................................................................................... XIII

CHAPTER 1: INTRODUCTION .................................................................................. 1

1.1 Overview .............................................................................................................. 1

1.2 Knowledge gaps ................................................................................................... 6

1.3 Hypotheses ........................................................................................................... 6

CHAPTER 2: LITERATURE REVIEW ....................................................................... 9

2.1 Impacts of climate change .................................................................................... 9

2.2 Climate change and occupational health ............................................................ 10

2.3 Workplace heat exposure and occupational health ............................................ 11

2.4 Heat exposure and urolithiasis ........................................................................... 12

2.5 Study designs assessing the effects of occupational heat exposure on urolithiasis

.................................................................................................................................. 13

2.6 Risk factors for heat-induced urolithiasis........................................................... 20

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2.7 Knowledge gaps ................................................................................................. 23

CHAPTER 3: STUDY DESIGN AND METHODS ................................................... 33

3.1 Aims and objectives ........................................................................................... 33

3.1.1 Aims............................................................................................................. 33

3.1.2 Specific objectives ....................................................................................... 33

3.2 Research design and data collection................................................................... 33

3.2.1 Research design ........................................................................................... 33

3.2.2 Study setting ................................................................................................ 34

3.2.3 Data collection ............................................................................................. 37

3.2.4 Criteria for selection .................................................................................... 38

3.3 Data analysis ...................................................................................................... 43

3.3.1 Descriptive statistics .................................................................................... 43

3.3.2 Univariate analysis ...................................................................................... 44

3.3.3 Selecting variables for modelling process ................................................... 44

3.3.4 Bivariate and multivariable modelling ........................................................ 45

CHAPTER 4: RESULTS ............................................................................................. 53

4.1 Descriptive statistics and univariate analyses .................................................... 53

4.2 Overlapping effect .............................................................................................. 58

4.3 Association between risk factors and urolithiasis .............................................. 59

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4.4 Sensitivity test of the multivariable model ......................................................... 61

CHAPTER 5: DISCUSSION AND CONCLUSION .................................................. 65

5.1 Key findings in this study .................................................................................. 65

5.2 Public health implications .................................................................................. 65

5.3 Recommendations .............................................................................................. 67

5.4 Alternative explanations ..................................................................................... 71

5.4.1 Chance ......................................................................................................... 71

5.4.2 Bias .............................................................................................................. 72

5.5 Comparison with other studies ........................................................................... 73

5.5.1 Previous studies on ambient heat and urolithiasis ....................................... 73

5.5.2 General comparisons of study designs and results ...................................... 75

5.5.3 Association between total exposure time and urolithiasis ........................... 77

5.5.4 Association between the type of work and urolithiasis ............................... 78

5.5.5 Association between hypertension and urolithiasis ..................................... 85

5.6 Strengths and limitations .................................................................................... 86

5.7 Directions for future research ............................................................................. 88

5.8 Conclusions ........................................................................................................ 90

REFERENCES ............................................................................................................ 91

APPENDIX 1: Tables of Results for Statistical Analyses ......................................... 107

APPENDIX 2: Ethics Application Exempt ............................................................... 121

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APPENDIX 3: GIHI Approval Letter........................................................................ 123

APPENDIX 4: Information Collection Form to OHSOs ........................................... 125

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LIST OF TABLES

Table 1. Characteristics of previous studies assessing the effects of heat exposure on

urolithiasis .................................................................................................................... 26

Table 2. Metabolic evaluation for explaining heat-induced urolithiasis...................... 30

Table 3. Descriptive statistics and univariate analysis of variables ............................. 57

Table 4. Overlapping effect between type of work and department ............................ 58

Table 5. Odds ratios of risk factors of urolithiasis in the conditional logistic regression

model............................................................................................................................ 60

Table 6. Odds ratios of risk factors for urolithiasis in the conditional logistic

regression model for a sensitivity test .......................................................................... 62

Table 7. Threshold WBGT levels for different workloads among men normally

clothed, acclimatized, physically fit and in good health .............................................. 80

Table 8. Modification of threshold WBGT level by different conditions ................... 80

Table 9. Threshold WBGT limits ................................................................................ 82

Table 10. Non-climate factors impacting on heat stress of different types of work and

relevant odds ratios of urolithiasis ............................................................................... 84

Table 11. Summary of strengths and limitations of this study .................................... 88

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LIST OF FIGURES

Figure 1. Atmosphere-Ocean General Circulation Model projections of surface

warming ....................................................................................................................... 2

Figure 2. Scatter plot of prevalence rates for kidney stones in the United States by

state ................................................................................................................................ 3

Figure 3. Predicted growth in high-risk area (stone belt; risk ratio ≥ 1.2) vs. time 2000

(yellow), 2050 (orange), and 2095 (red); linear model. At 2000 41% of the population

within a high-risk zone, 56% at 2050, and 95% at 2095, based on year 2000

population distribution ................................................................................................... 4

Figure 4. The location of Guangzhou City (the area of yellow colour) ....................... 35

Figure 5. Mean monthly temperature in Guangzhou City ........................................... 36

Figure 6. Bar graph of percentages by three levels of total exposure time .................. 54

Figure 7. Bar graph of percentages by three levels of total exposure time among eight

types of work................................................................................................................ 55

Figure 8. Odds ratios and 95% confidence intervals for seven different types of work

...................................................................................................................................... 61

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LIST OF ABBREVIATIONS

BP: Blood Pressure

CI: Confidence Interval

DALYs: Disability Adjusted Life Years

ECG: Electrocardiogram

GEE: Generalized Estimating Equations

GHG: Greenhouse Gas

25-HCC: 25-Hydroxycholecalciferol

iPTH: intact Parathyroid Hormone

IPCC: Intergovernmental Panel on Climate Change

ISO: International Organization for Standardization

OHSO: Occupational Health and Safety Officer

OR: Odds Ratio

PPE: Personal Protective Equipment

UV: Ultraviolet

WBGT: Wet Bulb Globe Temperature

WHO: World Health Organisation

25(OH)D: 25-hydroxyvitamin D

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STATEMENT OF AUTHORSHIP

The work contained in this thesis has not been previously submitted to meet

requirements for an award at this or any other higher education institution. To the best

of my knowledge and belief, the thesis contains no material previously published or

written by another person except where due reference is made.

Signature:

Date: 30th

July 2012

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ACKNOWLEDGEMENTS

I would like to thank my three supervisors Prof. Shilu Tong (Principal Supervisor), Dr.

Cameron Hurst (Associate Supervisor) and Dr. Lyle Turner (Associate Supervisor).

Prof. Tong, his enthusiasm, insight and dedication to the advancement in

environmental and public health research are inspirational. His academic, empirical

and prompt advice and comments on my study were highly valuable. I really

appreciate his guidance and support for my study design, data collection, analyses and

thesis writing. Dr. Hurst, as an experienced biostatistician, had given me valuable

statistical advice on data analysis and writing of my thesis. I feel grateful for his

support on statistical data analysis and professional encouragement to help me move

forward. Dr. Turner had shared with me his research experience, his patience and

willingness to help during my study. I thank him for his support and friendship.

I would like to acknowledge the School of Public Health and Social Work, Institute of

Health and Biomedical Innovation, QUT, for funding this study and for all the support

in my research.

I would like to acknowledge Guangdong Institute of Health Inspection for providing

the health surveillance data in this study.

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I would also like to thank my family and friends for their encouragement and

emotional support, and particularly my husband, for encouraging me to pursue higher

degrees in research. I greatly appreciate all their unconditional love and support

throughout my study.

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CHAPTER 1: INTRODUCTION

1.1 Overview

Prolonged exposure to a hot work environment can bring about heat-induced

disorders, such as dehydration, heat rash, fatigue, heat cramps, syncope, and

heatstroke [1]. Symptomatic exhaustion and clinical diseases, particularly urolithiasis,

can also occur as a result of excessive heat exposure [2, 3]. Some factors may increase

or decrease individual susceptibility (e.g. age, obesity and pre-existing medical

conditions), and socio-economic status may also play a role in how heat exposure will

impact on workers‟ health [4].

There is clear evidence that at current levels of economic growth, global emissions of

greenhouse gas (GHG) will continue to grow over the coming few decades [5]. In the

most recent Intergovernmental Panel on Climate Change (IPCC) Assessment Report

in 2007, it was projected that global average temperatures will increase by 1.1–6.4 °C

by 2100 (with the most likely range being 2 to 4 °C) (See Figure 1) [6]. This would

result in the warmest period on the Earth for at least the last 100,000 years [7].

Climate change is likely to impact on occupational health and safety across all sectors

of industry [4]. For example, outdoor workers will face hotter conditions and

increased exposure to higher ambient temperatures.

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Figure 1. Atmosphere-Ocean General Circulation Model projections of surface

warming (Source: IPCC, 2007 [6])

Urolithiasis, or kidney stone disease, is a common disease across the world [8]. The

average global prevalence of urolithiasis was 3.3% in the 1980s and 5.6% in the

1990s [9, 10]. The highest prevalence rates were for uranium workers in eastern

Tennessee (18.5%) and adults in northeast Thailand (16.9%) [11, 12]. Although the

underlying cause for urolithiasis is still not clear, a great number of studies have

suggested ambient temperature as a contributor to kidney stone formation [2]. The

prevalence of urolithiasis has shown noticeable geographic variability. In the US, the

southeast has been reported to have as much as a 50% higher prevalence than the

northwest. Mean annual temperature has been estimated to account for 70% or more

of this variability, with other risk factors such as age, gender, race, diet, family history,

social class and sunlight index found to potentially account for the remainder [13].

Results by Fakheri and Goldfarb [2] demonstrated that mean annual temperature was

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positively correlated with the prevalence of urolithiasis and men were more

vulnerable than women to heat-induced urolithiasis (See Figure 2).

Figure 2. Scatter plot of prevalence rates for kidney stones in the United States by

state (Source: Fakheri and Goldfarb, 2011 [2])

In recent years, urolithiasis has attracted much attention because of climate change [2,

13]. It has been projected that the nationwide prevalence of urolithiasis attributable to

climate change in the United States will probably increase from 5.2% in 1988–1994 to

10.4% (linear model) by 2050 [13] (See Figure 3).

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Figure 3. Predicted growth in high-risk area (stone belt; risk ratio ≥ 1.2) vs. time 2000

(yellow), 2050 (orange), and 2095 (red); linear model. At 2000 41% of the population

within a high-risk zone, 56% at 2050, and 95% at 2095, based on year 2000

population distribution. (Source: Brikowski et al., 2008 [13])

Heat is an important occupational health issue because its effects are likely to impair

workers‟ health and consequently their productivity [14]. Outdoor workers in tropical

and subtropical areas, particularly in low and middle-income countries, are at highest

risk of outdoor heat exposure, because outdoor workers in these countries engage in

heavy physical activities in hot environment [15]. Occupational heat exposure as a

possible contributor to urolithiasis formation was firstly reported in 1945 by Pierce et

al. [16]. The researchers found that the incidence of urolithiasis among American

troops in the desert area was two times higher than in the mountainous area. Since

then, a number of epidemiological studies have been conducted to explore the

association between occupational heat exposure and urolithiasis among engineers [17],

lifeguards [18], marathon runners [19], machinists [20] and steel workers [21]. Most

of these studies were carried out in developed countries.

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An increase in workplace heat exposure due to climate change is likely to create a

range of occupational health problem including urolithiasis. However, the potential

impacts of climate change on occupational safety and workers‟ health remain largely

unknown currently, with most previous research focusing on the health impacts of the

general population rather than on the working population [4, 22]. This is in part due to

the lack of useful data relevant to this relatively new area of occupational health

research [4].

China is a rapidly developing country that has experienced a general trend of

temperature increases since the late 1980s, in line with the global pattern [23]. China

has lots of labour-intensive industries, e.g. shipbuilding, construction, stevedoring

services and mining, and it has a large proportion of the world‟s manufacturing

workers. Many of these workers are exposed to ambient heat in poor working

conditions, with heavy workloads and low incomes. They are generally from poor

families with little education, and receive no or very little training about occupational

health. They have extremely low awareness and understanding of how to prevent

urolithiasis at the workplace. They usually have no regular urolithiasis screening

programs, and no adequate water breaks and free drinking water supplies.

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1.2 Knowledge gaps

Up to now, most previous studies have examined the association between

occupational ambient heat exposure and urolithiasis in developed countries [16-20,

24-27]. Very few studies have explored the impacts of ambient heat on urolithiasis

among working populations in developing countries, such as China. Additionally,

most of these studies were descriptive or cross-sectional in design. Therefore,

previous studies have been unable to make a causal inference because both health and

ambient temperature data were collected at the same time. Thus, analytical designs

such as a case-control or cohort design should be employed if feasible. This study

aimed to determine the association between ambient heat exposure and urolithiasis

among workers in a large shipbuilding company in Guangzhou, Guangdong Province,

China, using a case-control study design.

1.3 Hypotheses

Hypotheses for this study are:

1. H1: There is an association between ambient heat exposure and urolithiasis

among outdoor workers in China.

H0: There is no association between ambient heat exposure and urolithiasis

among outdoor workers in China.

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2. H1: Workers with longer exposure time, certain types of work or relevant

cardiovascular diseases are more likely to have urolithiasis.

H0: There is no association of exposure time, certain types of work or relevant

cardiovascular diseases with urolithiasis.

This thesis is composed of five chapters. The first chapter is an introduction; the

second is a literature review of occupational heat exposure and urolithiasis; the third

describes the design and methods used in this research; the fourth presents the results;

and, the fifth contains discussions, recommendations, and conclusions.

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CHAPTER 2: LITERATURE REVIEW

2.1 Impacts of climate change

There is a global scientific consensus that the Earth is warming, due to GHG

emissions caused by human activity [6]. The IPCC has concluded that “warming of

the climate system is unequivocal, as is now evident from observations of increases in

global average air and ocean temperatures, widespread melting of snow and ice, and

rising global average sea level” [6]. In the last century, the Earth has warmed by

approximately 0.75 °C and global sea levels have risen by over 4 cm. Eleven of the

twelve years from 1995–2006 were ranked among the twelve warmest years on

records globally since 1850 [6].

Climate change is one of the most critical issues facing the global community [7].

Because the climate is changing rapidly, it has the potential to significantly impact the

global environment, society and economy [28]. The impacts of climate change will be

broad and complex, and may have far reaching consequences on all parts of society

[4]. Climate change has been increasingly recognised as the biggest global health

threat of the 21st century [29]. A great number of studies have indicated that climate

change can affect human health directly and indirectly. Direct health impacts include

heat-induced mortality and morbidity, such as deaths and illnesses due to heat-waves

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[30-32]. Indirect impacts include climate-mediated changes in the incidence of

infectious diseases, such as geographical and seasonal changes in incidences of

malaria, dengue, tick-borne viral disease and schistosomiasis [33-35], and the

prevalence of chronic diseases, such as urolithiasis, lung disease and heart diseases [2,

3, 22].

2.2 Climate change and occupational health

Climate change is likely to impact on occupational health and safety across all sectors

of industry [4]. For example, outdoor workers will face hotter conditions and

increased exposure to higher ambient temperatures. The predicted increase in the

intensity of ultraviolet (UV) radiation may also present further hazards to outdoor

workers [1].

As strategies to promote effective climate change adaptation are now being

implemented, the occupational health community should play an important role in

both understanding the impacts of climate change and minimising these impacts [4].

How is climate change related to occupational safety and workers‟ health? Will the

impacts of climate change on the working population be different to impacts on the

general population? Many questions remain to be answered. Recently, a framework

has been developed by Schulte and Chun [1] to help identify how climate change can

affect occupational health and safety. The hazards were grouped into seven categories:

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(1) increased ambient temperature; (2) UV radiation; (3) air pollution (resulting from

increased temperatures, ozone levels and airborne particles); (4) extreme weather; (5)

expanded vector habitat; (6) industrial transitions and emerging technologies; and (7)

changes in the built environment [1]. However, uncertainty remains in attributing

occupation-related health effects to climate change because of the lack of long-term

and high-quality datasets. Additionally, the role of a range of confounders (e.g. socio-

economic factors) remains unclear [30].

2.3 Workplace heat exposure and occupational health

An increase in workplace heat exposure due to climate change is likely to create

occupational health risks and have a significant impact on workers‟ productivity. The

human body maintains a core body temperature of between 36–37.2 °C. A person

carrying out physical activities creates metabolic heat inside the body, which needs to

be transferred to the outside environment in order to avoid an increase in the core

body temperature. The heat transfer between the human body and outside

environment depends on both the ambient air temperature and the type of clothing. If

ambient temperatures exceed 35 °C, the human body can only maintain normal core

body temperature by sweat evaporation [22].

Effective measures (e.g. air conditioning) to reduce workplace heat exposure can be

practical for indoor environments, but such control is much more difficult in outdoor

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environments. To avoid midday work capacity loss, some people may choose to work

at night time or work during cooler parts of each day. However, night work is not

possible for many workers who must work during daylight [22].

2.4 Heat exposure and urolithiasis

Dehydration induced by sweating is one main mechanism for heat exposure causing

urolithiasis [33]. Continuous sweating leads to body dehydration represented by the

loss of extracellular fluid. This induces an increase in serum osmolality which in turn

causes vasopressin secretion by the posterior pituitary. This leads to reduced urinary

volume and increased urinary concentration, including the concentration of relatively

insoluble salts. When the concentration of these salts exceeds their upper limit of

solubility, the salts precipitate and form solid crystals that develop into stones [36].

If heat exposure and sunlight are experienced together, another mechanism for

causing urolithiasis exists besides dehydration. Increased urinary calcium excretion

attributed to sunlight accelerates the formation of urolithiasis [35]. Sunlight exposure

facilitates the generation of serum 25-hydroxycholecalciferol (25-HCC), which can be

converted to 25-hydroxyvitamin D (25(OH)D) in the kidneys [35]. 25(OH)D is

associated with increasing urinary calcium excretion [37, 38]. Excessive urinary

calcium excretion (hypercalciuria) is an important contributor to urolithiasis in the

pathogenesis process [39].

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2.5 Study designs assessing the effects of occupational heat exposure on

urolithiasis

To understand previous studies on the effects of occupational heat exposure on

urolithiasis and find knowledge gaps in this area, a literature search was conducted in

April 2011, using the electronic databases PubMed, Scopus, ScienceDirect, and ISI

Web of Science. The search was limited to English language articles published in

peer-reviewed journals from all years up to December 2011. The key words used in

the literature search included: heat, temperature, urolithiasis, kidney stone,

nephrolithiasis, occupation and workers. References and citations of the articles

identified were manually checked to ensure that all relevant published literature was

included.

In total, ten studies [16-21, 24-27] were identified through the literature search. These

studies were conducted in different parts of the world, including the countries of

Brazil [21], Japan [27], Italy [20], Singapore [26], Scotland [25], Israel [18], the

United Kingdom [24], the United States [16, 19], regions of the Persian Gulf [24], the

Mediterranean, the Middle East and the Far East [17]. Nine of these studies were

conducted in developed countries except for one which was carried out in a

developing country Brazil. Their publication dates ranged from 1945 to 2005.

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A number of studies have assessed the effects of heat exposure on urolithiasis. Most

of these studies have reported a positive association between heat exposure and

urolithiasis [16, 18-21, 24-26]. However, some researchers found no association, such

as one Japanese study performed by Iguchi et al. [27] showing administrative workers

without heat exposure had a higher urolithiasis prevalence than farmers and lumber

workers with heat exposure.

Through the literature review, various study designs have been applied to explore the

relationship between heat exposure and urolithiasis. Two case studies described that

increased heat exposure seems to raise the incidence of urolithiasis, and showed a

potential relationship between heat exposure and urolithiasis [16, 25]. Six cross-

sectional studies explored a possible association between heat exposure and

urolithiasis among outdoor occupations (i.e. lifeguards, marathon runners, quarry

drilling and crusher workers, quarry truck and loader drivers and postal deliverymen),

and indoor occupations (i.e. engineers, steel plant workers and glass plant workers)

[18-21, 26]. One cohort study analysed the association between sunlight exposure and

hypercalciuria and found that increased sunlight exposure increased the excretion of

urine calcium. This was relevant to the association between heat exposure and

urolithiasis [24]. Another cohort study focused on studying the pattern of incidence of

urolithiasis among engineers exposed to heat in the engine room, and found that the

incidence of urolithiasis decreased after the temperature decreased in the engine room

[17].

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Two case studies were from the United States [16] and the United Kingdom [25]. The

first study published in 1945 was performed by Pierce et al. [16], which evaluated the

detailed information in medical records of 61 newly proven urolithiasis cases among

American troops in an overseas desert area. They found that the number of urolithiasis

cases increased during the hot months and decreased during the cool months. They

stated that the incidence of urolithiasis among soldiers in the desert area was twice as

high as that for those in the mountainous area, however the exact incidence was not

demonstrated due to military security [16]. Ferrie et al. [25] performed another case

study on examining the profiles of 47 urolithiasis patients from a clinic in the

Glasgow area, Scotland. They found that 27 out of 47 (57.5%) patients in total had an

occupational history of hot-metal exposure [25]. These two studies described the

possible association between heat exposure and urolithiasis.

Six cross-sectional studies were based separately in Israel [18], the United States [19],

Japan [27], Singapore [26], Italy [20], and Brazil [21], with the first four focusing on

outdoor workers and the latter two on indoor workers.

Better et al. [18] examined the prevalence of urolithiasis between 45 lifeguards and 50

people from the general population with similar age, sex and season in Israel. They

found that lifeguards had a ten-fold greater risk of urolithiasis than the general

population. Milvy et al. [19] compared the prevalence of urolithiasis between 1977

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New York marathon runners and the matched general population (from census data)

in the United States. They reported that 19 of the 1,832 marathon runners had

urolithiasis, and the prevalence of urolithiasis among marathon runners was 4.5 times

higher than that of an age-matched group from census data. Pin et al. [26] carried out

a cross-sectional study in Singapore comparing the prevalence of urolithiasis between

several outdoor and indoor occupations involving different levels of physical activity.

They found that outdoor workers had five times higher prevalence of urolithiasis than

indoor workers. However, there was no statistical difference in the prevalence of

urolithiasis between physically active and inactive workers. Iguchi et al. [27] carried

out a survey among 1,972 randomly selected inhabitants of Kaizuka, Japan aged 20 to

59. They found the prevalence of urolithiasis in administrative workers was 19.6%,

which was significantly higher than any other occupations including outdoor workers

(e.g. farmers and lumber workers). Their result was inconsistent with most other

relevant studies [16-20, 24-26]. However, farmers and lumber workers consisted of a

very low fraction (1.3%) of the total respondents, which was referred to as a small

sample size of 25 men and women in total. This was a potential reason for explaining

why the study did not found any cases within the farmers and lumber workers group.

These four studies [18, 19, 26, 27] assessed the association between ambient heat

exposure and urolithiasis. However, the first two did not independently examine the

impact of ambient heat but interact with other risk factors. For example, lifeguards

were exposed to strong sunlight and ambient heat together, and marathon runners

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undertook intensive physical activities when exposed to ambient heat [18, 19].

Meanwhile, the latter two studies may have suffered from biases in the homogeneity

of their subjects. For instance, Pin et al. [26] conducted their study by combining

different kinds of workers together including quarry drilling and crusher workers,

quarry truck and loader drivers and postal deliverymen as outdoor workers. These

workers were from different kinds of industries where occupational heat and sunlight

exposure differed markedly, and they also had different diet and health status. Similar

biases may exist between farmers and lumber workers in the study performed by

Iguchi et al. [27].

Borghi et al. [20] and Atan et al. [21] carried out cross-sectional studies on heat-

exposed and non-heat-exposed workers in a steel plant and a glass plant, respectively.

Both studies controlled many risk factors, including age, race, family history, diet,

and relevant diseases between the heat-exposed group and the non-heat-exposed

group. Statistical analyses showed significant differences between the two groups [20,

21, 40]. In Borghi et al.‟s study [20], male glass plant workers chronically exposed to

heat stress had more than three times higher risk of urolithiasis than those working at

room temperature. In Atan et al.‟s study [21], heat-exposed male workers were found

to have a ten-fold greater risk of urolithiasis than non-heat-exposed workers [21].

These two were the most recent studies on indoor workplace heat exposure and

urolithiasis. Both studies [20, 21] examined the changes in urinary biochemistry

which was mainly attributed to low urinary volume and led to calcium salts

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supersaturation. They demonstrated the association between indoor heat exposure and

urolithiasis.

Parry et al. [24] conducted a cohort study on two groups of soldiers transported from

the United Kingdom to the Persian Gulf during both the cold and hot seasons.

However, this study only showed the possible association between ambient heat

exposure and hypercalciuria. They compared the difference of urinary calcium levels

among the same group of soldiers before and after being transported for ten days.

They also compared urinary calcium levels between the two groups at the time when

the summer-transported group arrived in Persian Gulf for 10 days and the winter-

transported group had already stationed in Persian Gulf for 8 months. A significant

increase of urinary calcium excretion was only observed in the summer-transported

group ten days after arrival. Parry et al. [24] argued that the difference between the

winter transported group and the summer transported group was most likely due to

increased exposure to sunlight rather than higher temperatures and decreased

humidity, because other researchers observed that ultraviolet light exposure increased

the excretion of calcium, and the summer transported group received a much longer

period of extra sunlight (5.22 hours per day) than the winter transported group (1.73

hours per day) with rises of 19.5 °C and 12 °C, respectively. Although it was reported

that 2 of 91 soldiers followed up for three years had urolithiasis, the incidence of

urolithiasis among soldiers in Service during the same period in the United Kingdom

or that among the general population was not provided for comparison. Thus, this

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cohort study mainly indicates the association between sunlight and hypercalciuria, but

also suggests the possible association between both sunlight and ambient heat

exposure and urolithiasis.

Another cohort study was carried out by Blacklock et al. [17] to analyse the pattern of

incidence of urolithiasis in the British Navy over seven years (1958–1964). They

found that the incidence of urolithiasis was higher among engineers who were often

exposed to heat in the engine room. However, their incidence of urolithiasis

significantly declined year by year after air-conditioners were introduced. Thus, it was

considered that the decline in urolithiasis was associated with decreased heat exposure.

However, the study did not report how many engineers were lost to follow up during

the study period, and whether the incidence of urolithiasis in different years had been

modified according to the changed number of follow-up engineers. Nevertheless, this

study provided useful evidence for the association between indoor heat exposure and

urolithiasis.

In total, nine studies indicated that the prevalence of urolithiasis was higher among

groups with heat exposure at workplaces than those without [16-21, 24-26], while

only one study failed to identify such an association [27]. The relative risk of

urolithiasis was found to be between two and ten times higher among heat-exposed

workers than non-heat-exposed ones (See Table 1).

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2.6 Risk factors for heat-induced urolithiasis

Some cross-sectional studies [18, 20, 21] carried out metabolic evaluation to support

the association between heat exposure and urolithiasis. Risk factors such as length of

service, age, and social class have also been taken into consideration in these studies.

For example, age was a proven risk factor in many epidemiological studies on

urolithiasis [41-43] and was usually controlled for research purposes.

Three studies attempted to demonstrate the mechanism of heat-induced urolithiasis

formation in relation to biochemical changes in urine generated by heat exposure [18,

20, 21]. The association between metabolic changes and urolithiasis has been proven

through clinical studies [44, 45]. The following epidemiological studies also found a

link between biochemical changes and heat exposure. Atan et al. [21] performed a

urine metabolic evaluation among 59 workers without urolithiasis (34 heat-exposed

workers and 25 non-heat-exposed workers), finding significantly low urine volume

and hypocitraturia for heat-exposed workers. Borghi et al. [20] conducted a three-day

examination on 8-hour shift workers without urolithiasis in a glass plant, which

consisted of 21 randomly selected workers with and 21 workers without heat exposure.

Various indexes were tested for metabolic changes in urine samples, including uric

acid, pH value and specific gravity. A high level of uric acid, lower pH values and a

higher specific gravity were found in the heat-exposed group. Better et al. [18]

estimated calcium metabolism using blood and urine samples from 45 lifeguards and

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20 controls from the general population matched with sex, age and season. Serum and

urine changes were measured, and hyperuricemia, higher serum level of 25-HCC, and

lower serum level of intact parathyroid hormone (iPTH) were observed among

lifeguards.

These studies provided information on biochemical changes associated with

dehydration and calcium excretion. Dehydration can cause low urine volume, high

specific gravity, high uric acid, hyperuricemia, and low pH [2]. Urinary calcium

excretion increase was attributed to high levels of serum 25-HCC induced by

increased sunlight exposure, being accompanied with low iPTH and a decreased

Mg/Ca ratio [34]. Dehydration and urinary calcium excretion increase were two well-

recognised risk factors for urolithiasis formation [46].

Length of service is an indicator for the cumulative amount of occupational heat

exposure if subjects have an equivalent dose of daily exposure. It is especially reliable

for stable jobs if someone continues doing the same type of work for a very long

period of time. There are mixed reports about the association between the length of

service and urolithiasis. For example, Atan et al. [21] found no significant difference

in the length of service between heat-exposed and non-heat-exposed groups. However,

Better et al. [18] found that lifeguards with a longer length of service were more likely

to suffer from urolithiasis than those with shorter periods of service.

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Social class is another possible risk factor for urolithiasis in studies examining heat-

induced urolithiasis. Social class was considered to be linked with protein

consumption, viz. higher social classes having greater amount of protein consumption

than lower social classes [47]. Greater amounts of protein consumption was also

reported associated with urolithiasis formation [48]. However, Ferrie et al. [25]

studied the subjects‟ social classes and found no link between higher social class and

urolithiasis. In addition, a recent study reported that urolithiasis has spread to all

social classes as social and economic status has grown steadily [49]. Therefore,

influence of differing social classes on the prevalence of urolithiasis remains to be

determined [50-52].

Overall, the above risk factors provided important information for studying the

association between heat exposure and urolithiasis. Biochemical changes verified the

possible biomechanism in the impact of heat exposure on urolithiasis in previous

studies [18, 20, 21]. Length of service was a risk factor more closely related with

occupational heat exposure than other risk factors [18, 21], so it may be a useful

indicator for future research on occupational heat exposure and urolithiasis. Social

class used to be considered as an important predictor for urolithiasis [47] but it has

become less so in recent studies [49].

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2.7 Knowledge gaps

Previous studies have shown that workers worked with exogenous heat stress

(generally indoors), marathon runners, lifeguards, soldiers and outdoor workers

(quarry drilling and crusher workers, quarry truck and loader drivers and postal

deliverymen) exposed to sunlight had as two to ten-fold increased risk of urolithiasis

compared with the general population [16-21, 24-26]. A variety of designs have been

used to examine any difference in the prevalence of urolithiasis between heat-exposed

and non-heat-exposed populations in many parts of the world [16-21, 24-26]. Some

studies also conducted a metabolic evaluation to provide supportive evidence for

verifying the causality between heat exposure and urolithiasis [18, 20, 21, 24], or

examined other risk factors such as social class and length of service [18, 25]. These

studies provided a basic pattern of the association between heat exposure and

urolithiasis, however these studies do have some limitations.

Firstly, a cross-sectional design was commonly used to identify the possible

association between occupational heat exposure and urolithiasis, but very few studies

employed an analytical design (e.g. cohort or case-control), making it more difficult

to draw causal inference.

Secondly, very few studies examined the effects of ambient heat exposure on

urolithiasis among outdoor working populations. Previous studies had studied both

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lifeguards [18] and marathon runners [19] , but they might not be representative

samples for the general outdoor working populations. They were special working

populations exposed to ambient heat, high intensity sunlight with bare skin and/or

intensive physical activity at the same time. While Pin et al. [26] examined the

relationship between outdoor heat exposure (e.g. quarry drilling and crusher workers,

quarry truck and loader drivers and postal deliverymen) and urolithiasis, this study

was conducted in Singapore, which is a tropical, developed country. It is unlikely

their findings could be generalised to developing countries like China.

Thirdly, more attention should be paid to studying the effects of heat exposure on

urolithiasis among working populations in developing countries. Most previous

studies on occupational heat exposure and urolithiasis were carried out in developed

countries including the United States [16, 19], the United Kingdom [17, 24, 25], Israel

[18], Singapore [26], Italy [20] and Japan [27]. Only one is from a developing country

(Brazil) [21]. However, the situation in developing countries may be worse than

developed countries due to lower awareness of occupational health and lower income.

Therefore, the risk of occupational heat exposure for urolithiasis in many developing

countries remains to be determined.

Climate change is likely to put additional stress on ambient-heat-exposed working

populations [53, 54]. Based on this literature review, heat exposure may play an

important role in urolithiasis genesis. To the best of our knowledge, no study has

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examined the association between ambient heat exposure and urolithiasis in a

developing country in Asia. It is necessary to conduct a study in China as it has the

largest manufacturing working population in the world, with large proportion of

workers exposed to ambient heat through industries such as shipbuilding, construction

and stevedoring service.

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Table 1. Characteristics of previous studies assessing the effects of heat exposure on urolithiasis

Study and location Research Design Analysis methods Subject Exposure time Key findings

Atan, et al., 2005 [21],

Brazil

Cross-sectional Fisher‟s Exact Test and

Chi-square Test

10,326 male employees

working for more than 3

years at a large steel

plant

At least 3 years Workers exposed to high temperature had a higher

prevalence of urolithiasis (8.0%), ten times greater than

that for other workers (0.9%) not exposed to heat

(P<0.01).

Iguchi, et al., 1996 [27],

Japan

Cross-sectional Chi-square test,

Wilcoxon‟s rank-sum

test, and one-way

factorial analysis of

variance (ANOVA)

1,972 respondents of

3000 inhabitants

randomly selected from

20 to 59 years old in

Kaizuka City, Japan

Not mentioned The prevalence of urolithiasis among male administrative

workers was significantly higher than any other

occupational group, such as farmers and lumber workers.

Farmers and lumber workers without recorded stones

made up of the sample at 1.5%.

Borghi, et al., 1993

[20], Italy

Cross-sectional Chi-square test and

Student‟s t-test

236 man machinists

chronically exposed to a

hot environment in a

glass plant in Parma,

Italy and 165 workers

not exposed to heat in

the same factory

8hr/d, at least 6

months for 5

years

The prevalence of nephrolithiasis among heat exposed

machinists (8.5%) was three-fold higher than those not

exposed to heat (2.4%).

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Pin, et al., 1992 [26],

Singapore

Cross-sectional Not mentioned 406 male workers in

several occupations,

including outdoor

workers, e.g. quarry

drilling and crusher

workers, quarry truck

and loader drivers and

postal deliverymen;

indoor workers, e.g.

postal clerks and

hospital maintenance

workers

The outdoor workers had increased prevalence compared

with indoor workers (5.2% vs 0.85%, P<0.05).

Ferrie, et al., 1984 [25],

Scotland

Case study Descriptive statistic

including counts and

percentages

47 patients with

urolithiasis

(38 males and 9

females)

Hot-metal

exposure from 1

to 50 years

(average 19.0)

Individuals with an occupational history of hot metals

process exposure were more likely to develop

urolithiasis.

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Milvy, et al., 1981 [19],

the United States

Cross-sectional Not mentioned 1893 respondents of the

male participants in the

1977 New York City

Marathon

Not mentioned The prevalence among the marathon runners was 4.5

times greater than that of the matched population; the

prevalence of aberrant urine among respondents with

urolithiasis was nearly five times significantly higher

than that of those without urolithiasis.

Better, et al., 1980 [18],

Israel

Cross-sectional Student t-test 45 randomly selected

lifeguards out of a total

number of 120, and 50

people from the general

population matched for

sex, age and season

At least 8 hr/dy,

6 mo/yr

Lifeguards had an approximately ten-fold higher

prevalence of urolithiasis than the general population,

and lifeguards with urolithiasis had significantly longer

length of service than lifeguards without urolithiasis.

Parry, et al.,1975 [24],

the United Kingdom

and the Persian Gulf

Cohort Not mentioned Two groups of soldiers

(40 males in winter and

51 males in summer)

were transported from

the United Kingdom to

the Persian Gulf in cold

and hot seasons,

respectively

The group transported from the United Kingdom to the

Persian Gulf in summer had statistical significant

hypercalciuria while those in winter had not, which was

most likely to be caused by increased sunlight exposure.

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Blacklock, et al., 1965

[17], the Britain, the

Mediterranean, the

Middle East and the Far

East

Cohort Not mentioned The navy soldiers in

Service from 1958 to

1964 in British Royal

Navy

Not mentioned Engineers worked in the engine room of the ship had

higher incidence of urolithiasis; the incidence of

urolithiasis was declined year after year probably because

of the increasing use of air-conditioning in engine rooms

in ships.

Pierce, et al.,1945 [16],

an overseas desert

Case study Descriptive statistic

including counts

61 diagnosed

urolithiasis cases among

a command of

American troops in an

overseas desert area

Not mentioned There was a relatively short period for urolithiasis

formation in the desert area; the prevalence of urolithiasis

among soldiers in the desert area was two times higher

than in the mountainous area.

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Table 2. Metabolic evaluation for explaining heat-induced urolithiasis

Reference Subject

Selection criteria for

metabolic evaluation

Risk factors Key findings Comment

Atan, et

al., 2005

[21]

34 heat-exposed

workers and 25

non-heat-

exposed workers

Volunteer workers

without urolithiasis

Calcium, creatinine, uric

acid in serum; volume,

calcium, uric acid, citrate

and oxalate in 24 hours urine

Heat-exposed workers had greater

frequency of hypocitraturia

(P=0.03) and lower urinary

volume (P=0.01).

Hypocitraturia and low urinary volume

were proved risk factors for urolithiasis;

the significant difference on hypercitraturia

and low urinary volume between heat-

exposed workers and non-heat-exposed

workers supported the causal association

between heat exposure and urolithiasis.

Borghi, et

al., 1993

[20]

21 heat-exposed

workers and 21

non-heat-

exposed workers

Randomly selected;

without urolithiais,

family history, gout or

medications; examining

social class and dietary

habits

Volume, sodium, potassium,

calcium and magnesium,

chloride, creatine, uric acid,

phosphate, sulphate, oxalate,

citrate, ammonium, specific

gravity, pH, calcium

oxalate, calcium phosphate

and struvite

Fluid intake was significantly

different between heat-exposed

workers and non-heat-exposed

workers; uric acid was

significantly greater; pH was

significantly lower; specific

gravity was significantly higher.

Although fluid intake was greater among

heat-exposed workers, they still had higher

uric acid, lower pH and higher specific

gravity which were risk factors for

urolithiasis formation. This was supportive

evidence for the association between heat

exposure and urolithiasis.

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Better, el

al., 1980

[18]

45 lifeguards

were randomly

selected from

120 lifeguards in

Israel.

They were randomly

selected out of the

general population in

Israel, matched for sex,

age and season.

Serum 25-HCC, mean urine

calcium, hyperuricemia,

hypercalciuria, iPTH level,

daily urine volume and mean

Mg/Ca ratio

Lifeguards had significantly

higher level of serum 25-HCC,

mean urine calcium,

hyperuricemia and hypercalciuria

than the general population; iPTH

level, daily urine volume and

mean Mg/Ca ratio were

significantly lower than the

general population.

Results of the metabolic evaluation were

high risk factors for urolithiasis formation,

so they were supportive to the association

between sunlight exposure (heat) and

urolithiasis.

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CHAPTER 3: STUDY DESIGN AND METHODS

3.1 Aims and objectives

3.1.1 Aims

This study examined the association between ambient heat exposure and urolithiasis among

outdoor workers; and recommends strategies for minimising the impacts of ambient heat

exposure on urolithiasis among outdoor workers in China.

3.1.2 Specific objectives

Describe general demographic characteristics among cases and controls;

Quantify the relationship between outdoor heat exposure and urolithiasis;

Recommend strategies for minimising the impacts of ambient heat exposure on

urolithiasis among outdoor working populations in China.

3.2 Research design and data collection

3.2.1 Research design

A retrospective 1:4 matched case-control study was performed to investigate the association

between high ambient temperature exposure and urolithiasis among outdoor workers. The

statistical power of the study can be increased by selecting more than one control per case,

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however, there is usually little marginal increase in precision from increasing the ratio of

controls to cases beyond four [55, 56]. Thus 1:4 as the case/control ratio was selected for this

study. To calculate sample size Dupont‟s method was used [57] for sample size calculation

for this matched case-control study, and the minimum effect size is 163 (sets) (α=0.05,β

=0.2). The calculation was carried out after a literature review for estimating the expected

prevalence in the general population in Guangzhou, with an estimated result for the

prevalence of urolithiasis (4.9% for both sex) derived from a nearby city (Shenzhen) [58-60].

Due to little information available on this topic in literature, it was decided to use as many

cases as possible and 1:4 case/control ratio to maximise the statistical power in this pilot

study.

In order to collect necessary background information of subjects, a small investigation was

conducted on all occupational health and safety officers (OHSOs) in the company studied

using forms with brief questions (See APPENDIX Ⅳ Information Collection Form to

OHSOs). This helped to estimate the hottest period in summer at the workplace studied,

lengths for ambient heat exposure for different types of work and their workloads, and to

collect information out of health surveillance data including the highest temperature records,

the supply of free drinking water, supplies of free meals, the arrangement of water breaks,

and the historical records for urolithiasis treatments from 2003 to 2010.

3.2.2 Study setting

Research setting: A long established shipbuilding company in Guangzhou City,

Guangdong Province, China

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Guangzhou is the capital city of Guangdong Province in the southeast of China (See Figure

4). It is the third largest city in China, with a resident population of approximately 13 million

in 2010 according to the official statistical data [61]. It locates next to Hongkong with a total

area of 7434 km2

(22°26‟ to 23°56‟ north latitude, and 112°57‟ to 114°3‟ east longitude) [62].

As a subtropical city influenced by the Asian monsoon, Guangzhou has long summers that

are hot and humid, and short winters that are mild and dry. The Chinese meteorological

definition of summer is the period with average daily temperatures over 22 °C of at least 5

consecutive days. Summers of Guangzhou begin from May to October with mean monthly

temperature range between 25.9 to 28.6 °C [63] (See Figure 5). The mean annual temperature

of Guangzhou is 21.9 °C according to annual reports from Guangdong Meteorological

Bureau [63].

Figure 4. The location of Guangzhou City (the area of yellow colour)

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Figure 5. Mean monthly temperature in Guangzhou City

Source: Guangdong Meteorological Bureau, 2010 [63]

The shipbuilding company in this study is over 160 years old and is located in the

southeast of Guangzhou City. The average number of employees is approximately 1, 600 and

includes workers building and repairing ships in the open boatyard and employees working in

offices. Outdoor workers are exposed to high levels of heat from the sun. The highest

temperature is experienced during summer from two to four o‟clock in the afternoons

according to the records of the company‟s OHSOs. The highest temperatures records at

different locations varied, e.g. an outdoor cement floor temperature up to 42 °C, a deck

temperature up to 45 °C, and a cabin temperature up to 52 °C. According to the records from

its affiliated hospital (suggested by OHSOs), there are on average one to two outdoor workers

with transient effects of heat-related illnesses such as heat cramps or even heat fainting and

heatstroke during hot days in this company.

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3.2.3 Data collection

Ethics Application Exempt has been granted by the QUT University Human Research Ethics

Committee (See APPENDIX ⅡEthics Application Exempt). Guangdong Institute of Health

Inspection (GIHI) has also approved this study (See APPENDIX Ⅲ GIHI Approval Letter).

Researchers of this study promised to inform the management and workforce the research

findings and provide recommendations for the prevention of urolithiasis.

The health surveillance of workers was based on health checks performed according to

occupational health regulations in China [64]. Paper records of health surveillance data

covering 2003–2010 (available in 2003, 2005, 2007, 2008, 2009 and 2010) were collected

from the affiliated hospital of the shipbuilding company by occupational health inspectors at

Guangdong Institute of Health Inspection (GIHI). For the evaluation of the association

between occupational risk factors and urolithiasis among workers in the shipbuilding

company, researchers of this study worked with GIHI together to transfer the collected hard

copy data into an electronic version (without persons‟ names), and used the data for this study.

As these data were results of occupational health inspections, they were stored and assessed

within offices of GIHI according to the requirement of the approval from GIHI. Researchers

of this study therefore performed all data access and statistical analysis for the study on a

computer based in the GIHI office.

Prior to 2007, this company carried out health surveillance biennially, but changed to an

annual health check following this date. The total number of workers examined in the health

surveillance was 3288, which are twice as the annual average number of employees. This

number was made up of not only workers and employees continuously working during 2003

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to 2010, but also older workers and employees retiring, and new workers and employees

recruited during the same period of time. The company had expanded its workforce during

2009 to 2010 because of an increase in business volume. About half of these workers were

normally exposed to heat at work.

Data collected in the health surveillance system include: health surveillance ID, age, sex,

birth place, the type of work, the department, the length of service, kidney ultrasonography

results, electrocardiogram (ECG), blood pressure (BP), urine test, blood test, hepatitis B virus

infection test, and health check years. Parts of the above information, which were believed to

be closely relevant to urolithiasis and heat exposure, were selected for statistical analyses in

this study.

To investigate the ambient heat exposure of workers, OHSOs in the shipbuilding company

were invited to estimate average exposure time per day for different types of work based on

their observation and experience. The total exposure time for subjects (both cases and

controls) was then calculated according to the average exposure time per day and a worker‟s

length of service.

3.2.4 Criteria for selection

Cases were determined by the positive results of kidney ultrasonography. Ultrasound is an

effective and commonly used screening test for urolithiasis with a sensitivity of 98% and

specificity of 74% [51]. Controls were selected from those health check records with negative

results of kidney ultrasonography, with the criteria for selection as follows: the same sex and

similar age (± 1 year old) matched with cases in the closest health check years. The order of

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this selection procedure was sex, age, health check year, and health surveillance ID. For

example, when a male case was defined as 30 years old with health check in 2003, the

matched controls were selected from other 30 year old males with health check in 2003; this

selection process began from the male of the earliest health surveillance ID to the one of the

latest ID in 2003, e.g. from 440049000001 to 440049000002, then 440049000003. If the

health check file of an earlier health surveillance ID was lacking of some important

information, e.g. without information on type of work, department or BP, the next completed

health record file would be chosen as a control. When there was a lack of controls of 30 year

olds in 2003, controls amongst 30 year olds in 2005 would be checked instead. The rest were

selected in the same manner. If there was a lack of controls amongst 30 years old in all health

check years, controls amongst 31 or 29 year olds in the same health check year would be

checked beginning from the smallest health surveillance ID. A health surveillance ID could

only be chosen once in the process of subject selection. This avoided the situation of selecting

controls from cases that had passed out stones or had their stone removed surgically.

Missing values in the data set were less than 5%. A number of strategies were used to deal

with these missing values. Firstly, as the health surveillance data covered six years, some

missing values could be imputed by other years‟ health check records of the same subjects.

For example, if one‟s age was missing in the file of 2005 health check, the same information

from his or her health check files in 2003 and 2007 could be examined, and then his or her

age in 2005 could be calculated. Secondly, the definition of certain binary variables without

numerical results was clarified in the individual health check files. For the binary variables in

this study such as BP, besides those with the exact blood pressure results recorded, some

health check files in 2003 and 2005 did not contain the exact numeric BP results but only

reported “abnormal blood pressure” or “hypertension” or “normal” in the conclusion columns

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of health checks. Due to this situation, this study defined that those subjects with “abnormal

blood pressure” or “hypertension” recorded in the conclusions of health check files belong to

subjects of “hypertension”, and those with only “normal” in the conclusion columns of health

checks were subjects of “normal blood pressure”. Thirdly, certain variables were excluded if

they had over 10% of missing values. For example, although urine test was thought to be one

of the good non-invasive measurements for potential urolithiasis screening [65, 66], the

records of urine test were not included in this study because about 30% of these values were

missing.

The data were examined to identify outliers. Normal Q-Q plots were used to examine

whether there were outliers in the data collected. No outliers were identified in these data

through a preliminary analysis.

Age and sex were chosen as the matched criteria for the following reasons. Age is a

recognised risk factor for urolithiasis. Epidemiological studies have found that older people

are more likely to have urolithiasis [27, 67-69]. Sex was chosen because males have been

found to have a higher prevalence of urolithiasis than females [10, 69-71]. Although a recent

study reported no difference in the prevalence of urolithiasis in males [68], sex was still

chosen as a matched criterion.

In terms of diet, the company provided at least two meals per day on workdays, cases and

controls were considered that had similar diet. All cases and controls in the study were born

in Guangdong Province, and they had the same race. Because of the physical requirement for

heavy workloads, it is to be expected that the prevalence of metabolic diseases would be

lower in workers of the shipbuilding company than the general population.

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Possible risk factors in this study included type of work, department, total exposure time,

ECG and BP. The reasons for choosing these factors are explained below.

Type of work and department were the key occupational risk factors, and were used to

characterise the type of ambient heat exposure. These variables could not only reflect the

association between ambient heat exposure and urolithiasis, but could also categorise high

risk groups of outdoor workers. In this study, the subjects fell into eight work categories

including spray painter, smelter, welder, production security and quality inspector, assembler,

planing machine operator, gas-cutting worker and indoor employees. Six of these categories

worked mainly outdoors except for smelter and indoor employees who usually worked indoor.

Indoor employees were defined as employees working in rooms equipped with air-

conditioning. They consisted of executive staff in the company, teachers in its affiliated

kindergarten, primary school, middle school, and the medical staff in its affiliated hospital.

Department was also a risk factor, reflecting the association between work conditions

relevant to heat exposure and urolithiasis, however it was not used to define type of work due

to the fact that workers moved between departments regularly. For example, because the

shipbuilding and ship-repair departments shared workers from the same types of work

(including smelter, welder, production security and quality inspector, assembler, planing

machine operator, gas-cutting worker but not spray painter who was located only in ship-

repair department), when the volume of ships needing repair increased, the number of

workers in the ship-repair department would increase due to a movement of workers from the

shipbuilding department. As a result, the numbers of workers in the shipbuilding department

would also decrease. Given that the volume of workers in the ship-repair business was not

constant because clients would drop in when their ships were in need of repair due to

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42

accidents or corrosion, the numbers of workers in shipbuilding and ship-repair departments

could often fluctuate. Hence, while it was hard to specify fixed numbers for these two

departments, fixed numbers could be defined for types of work according to the fact that the

movement between job titles was seldom because the workers in this company were technical

workers who had to be trained and certified before going on duty. Therefore, department was

used in this study as the supplement for type of work. Four categories of departments were

used in this study, including shipbuilding, ship-repair, production security and indoor

departments. The production security department consisted of several sections including

production security, quality security, manufacture management and occupational safety

security. These sections had similar period of ambient heat exposure during daily work.

Indoor departments included the human resource department, the administrative office, the

sales department, the accounting department, the affiliated kindergarten, the affiliated

primary school, the middle school, the technical school and the affiliated hospital.

Length of service, average exposure time and total exposure time were used to determine the

extent of ambient heat exposure. These data were collected from the health surveillance data

directly. For cases, length of service was determined by the year when the worker entered the

company and the year of first diagnosis according to kidney ultrasonography results. Average

exposure time was estimated based mainly on types of work and OHSOs‟ daily observation

and experience. Thus, average exposure time was expressed in terms of hours per workday.

Total exposure time was calculated by multiplying the adjusted length of service by average

exposure time under some necessary unit conversion (e.g. converting „hour‟ into „day‟, then

into „year‟). According to the actual situation of 5 workdays per week and 6 hot months per

year in Guangzhou, every adjusted year of length of service was around 130 workdays of heat

exposure. The calculation formula was 365 × (5/7) × (6/12) ≈ 130 days. Average exposure

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43

time (hours) was multiplied by adjusted length of service (days) to get the result of total

exposure time (hours), and then the result was converted from hours into years.

Although the length of service could partly indicate cumulative heat exposure, it was not as

direct as total exposure time. Because total exposure time estimated the entire amount of heat

exposure for every worker or employee, the length of service only recorded the whole length

of employment from entering the company to the diagnosed time.

ECG result is a medical test that detects cardiac (heart) abnormalities by measuring the

electrical activity generated by the heart as it contracts. It is the most commonly performed

cardiac test reflecting heart diseases. Abnormal BP (hypertension) in this study was defined

as systolic blood pressure 140 mmHg or diastolic 90 mmHg or both. There are existing

occupational health policies that if workers have serious heart problems or/and hypertension,

they might be at risk when exposed to high levels of heat [49]. This means that heart disease

and hypertension are associated with heat exposure. Meanwhile, hypertension has also been

reported to be associated with urolithiasis [65]. So it is possible that abnormal ECG and

hypertension were risk factors for heat-related urolithiasis. Hence, the ECG and BP results

were included in this study as risk factors for occupational urolithiasis formation.

3.3 Data analysis

3.3.1 Descriptive statistics

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The characteristics (e.g. sex, age, type of work, department, length of service, average

exposure time and total exposure time) of cases and controls were examined using descriptive

statistics, which described the association between ambient heat exposure and urolithiasis.

3.3.2 Univariate analysis

As the data in this study were of a 1:4 design, they could not be simply analysed the same as

the 1:1 matched design; the strata of 1 case to 4 controls had to be taken into consideration. In

SPSS, the Generalized Estimating Equations (GEE) suite offers analysis within clusters

which can also fit to analyse the 1: n matched case-control data; and it can analyse variables

of different categories (e.g. scale variables, binary variables and nominal variables). This

study used GEE for the univariate analysis of scale variables (age, length of service, average

exposure time and total exposure time), binary variables (sex, BP and ECG) and nominal

variables (type of work and department). In order to understand more about the distribution

of different levels of total exposure time between cases and controls, total exposure time was

divided equally into three range groups representing low, medium and high levels of

exposure, and percentages of these three levels were compared between cases and controls.

The distribution (percentages) of low, medium and high levels of total exposure time among

eight types of work was also described.

3.3.3 Selecting variables for modelling process

Because total exposure time is a measure of average exposure time and length of service, they

were strongly correlated with each other. So it was necessary to select one of them for

entering into the multivariable model. Total exposure time was selected because it derives

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45

from ambient heat exposure and length of service and directly represents ambient heat

exposure.

As type of work and department provided similar occupational information from two

different layers, it was possible that they would suffer from collinearity when put into the

model together. In order to check whether there was collinearity with each other, both type of

work and department were put into the conditional logistic regression model together. If there

was collinearity, type of work would be chosen to put into the multivariable model with other

risk factors together for the main analyses, as type of work was more constant and could

provide more detailed information than department. Department could be used to test the

sensitivity of the final multivariable model.

3.3.4 Bivariate and multivariable modelling

A conditional logistic regression analysis by fitting a Cox regression model was used in the

modelling process. Model building used the purposeful selection of covariates approach [72].

3.3.4.1 Conditional logistic regression

The matched study is an important special case of the stratified case-control study. The

rationale for matched studies is discussed by Breslow and Day [73], Kleinbaum, Kupper, and

Morgenstern [72], Schlesselman [74], Kelsey, Thompson, and Evans [75] and Rothman and

Greenland [76], discussed the rationale for matched studies. In matched studies, subjects are

stratified on the basis of variables supposed to be associated with the outcome, so they do not

interfere with the covariates being studied. By design, a matched case-control study controls

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46

for the effect that is matched on. An assumption of matched design is that the effect of

covariates is expected to be the same across strata.

Conditional logistic regression is useful in investigating the association between an outcome

and a set of explanatory variables in a matched case-control study. The outcome in such a

study is whether the subject is a case or a control.

When there is one case and one control in a matched set, the matching is 1:1. A “trick” can be

used to allow a standard logistic regression approach to fit a conditional logistic regression.

For the ith

matched set, let ui to be the covariate vectors for the case and let vi1,…, vini be the

covariate vectors for the ni controls. The likelihood for the M matched sets is given by

M

in

j ij

i

i

v

u

11

)'exp(

)'exp()(

for the 1:1 matching, the likelihood is reduced to

M

i ii

i

vu

u

1 1 )'exp()'exp(

)'exp()(

by dividing the numerator and the denominator by exp (v‟i1β), one obtains

)'exp(1

)'exp()(

1

1

1 ii

iiM

i vu

vu

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47

When there is one case and multiple controls in a matched set, the matching is 1: n, Cox

regression can then be adapted to fit the conditional logistic regression model [43].

Cox regression is a widely used method, which was firstly introduced by Cox in 1972. It is

often used on censored survival or other time-to-event data for identifying differences in

survival due to treatment and prognostic factors in clinical studies.

The basic model is as the following:

λ (t, Xi) = λ0(t) exp (β‟ Xi)

for i =1,…, N.

N is the number of individuals in the study; T is the failure time and censored or not. So

its observed vector is (ti, δi, Xi). It assumes that the hazard function for failure time T for an

individual i with covariate vector X‟i= (x1i , x2i ,…,xki ,…,xKi) is the equation above [73].

The Cox model is a semi-parametric model since it does not specify the form of λ0(t).

However, it specifies the hazard ratio for any two individuals with covariate vectors X1 and

X2 [73], given that the ratio does not depend on time:

)]('exp[)'exp()(

)'exp()(

),(

),(21

20

10

2

1

t

t

t

t

(1)

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48

Therefore, this model is a proportional hazard regression model. It assumes that the failure

rates of any two individuals are proportional throughout the whole survival experience. If

X1=1, X2= 0, it becomes:

)'exp()(

)'exp()(

)0,(

),(

0

0

t

t

t

t

(2)

λ0 (t) is often termed the baseline hazard as it may be regarded as the hazard function of all

covariates are zero.

The model above is articulated for the purposes of modelling time-to-event data. However,

the use of this model for the conditional logistic regression needs modifications, and the

adapted Cox regression model can be used in matched case-control studies for estimating

proportional odds, rather than the proportional hazard. In this case the odds are substituted

into equation (1) and (2).

In SPSS 18.0, the Cox proportional hazard regression can be adapted to fit a conditional

logistic regression for 1: n matched case-control studies.

3.3.4.2 Purposeful selection of covariates

When selecting variables for inclusion in the regression model, there were two main aspects

to consider. Firstly, theoretically for the sake of obtaining a numerically stable and easily

generalizable model, the number of selected variables should be minimized. Secondly, from

the perspective of epidemiologic methodologists, in order to have a possible complete control

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49

of confounding [11, 77], all clinically and intuitively relevant variables should be included

into the model.

Hosmer [72] proposed a six-step approach to select covariates to build a multivariable model

which is appropriate for meeting the objectives illustrated above. This approach is called

“Purposeful Selection of Covariates” and while being mainly empirically driven, it allows the

researcher the discretion of ensuring that clinically important covariates are considered. It is a

method completely controlled by the researcher according to the research aim as opposed to

other statistical methods such as stepwise and best subsets selection [68]. This approach is

used here to build an appropriate conditional logistic regression model.

Step 1. Bivariate analysis

A bivariate analysis of each variable was conducted as the first step of the selection. This

produced crude odds ratios (ORs) estimates measuring the association between individual

risk factor and urolithiasis. Every variable was individually added to a conditional logistic

regression model to test whether it had a significant effect resulting in a table of crude ORs

and their corresponding P-values and confidence intervals.

Variables with „P-value<0.25‟ were added to enter an initial multivariable model in Step 2;

but those with „P-value>0.25‟ were excluded from bivariate analysis.

This screening criterion used in Step 1 for the variable selection was based on previous

studies on linear regression and logistic regression [68]. It showed that the traditional

inclusion criterion of P-value<0.05 often failed to identify variables known to be important

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50

[12, 78]. The higher P-value of 0.25 allowed the inclusion of all statistically significant

variables and those with the potential to be important confounders [68].

Step 2. Multivariable modelling

The second step was to fit an initial multivariable model with a set of covariates chosen from

Step 1; in this case, covariates with P-value<0.05 were kept in the model, and those with P-

value>0.05 were excluded.

Step 3. Reintroduce variables excluded from the initial multivariable model

The third step was to check whether the variables excluded from the initial multivariable

model are confounders, or have become significant in the new model. Also, at this step, it

was decided, according to the research aim, whether variables should be added to the model.

Following Step 2, covariates with P-value<0.05 were kept; and in this step, all variables with

P-value>0.05 were reintroduced one at a time into the model, and re-analysed to see whether

they were confounders or statistically significant.

A covariate was considered a confounder if its addition to the model resulted in a change≥20%

in the coefficient of covariates kept in the model. Confounders and variables important to the

research aim were kept in the model as well for the following steps.

Step 4. Reintroduce variables excluded from bivariate analysis

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The fourth step was to check whether the variables excluded from bivariate analysis were

confounders, or had become significant in the new model. Also, at this step any covariates

important to the research aims were added to the model.

After adjusting the multivariable model in Step3, variables excluded after bivariate analysis

were reintroduced into the model one at a time. This helped in identifying covariates that

were not significant by themselves but contributed to other present covariates, or were

identified as a confounder (as defined in step 3).

Step 5. Check for effect modification

The fifth step was to check whether the covariates remaining in the multivariable model

interacted with each other. That is, whether one covariate acted as an effect modifier of one

or more of the other covariates. An interaction was considered significant if the interaction

had a corresponding P-value<0.05. Only two way interactions were considered.

Step 6. Model adequacy

After checking the interaction of variables in Step 5, the final multivariable model was built.

Once the covariates to be included in the model were determined, the adequacy of the model

needed to be assessed. In the case of logistic regression models, this was done by simply

assessing overall model significance.

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After the main multivariable model was built, a sensitivity test using the same process was

conducted but replacing variables with variables of similar information, for example,

replacing “type of work” with “department”. Then the adequacy of the model was tested.

In this study, statistical analysis was performed using the SPSS 18.0 software package; in all

cases, two sided tests and a significance level of 0.05 were used.

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CHAPTER 4: RESULTS

4.1 Descriptive statistics and univariate analyses

In this study, there were 190 cases and 760 matched controls, with 83% of males among

cases and controls and the age range of total subjects being from 20 to 59 years. Age was also

matched well among cases and controls (38±11 years). Details are described in Table 3.

Length of service, average exposure time and total exposure time were three potential risk

factors indicating occupational ambient heat exposure. All these three were significantly

longer among cases compared with controls. Length of service of subjects ranged from 3 to

38 years, and was significantly longer among cases (17±11 years) than controls (16±11 years)

(P<0.01). Average exposure time ranged from 0.5 hours to 8 hours, and it was significantly

longer among cases (7±3 hours) than controls (5±3 hours) (P<0.01). Total exposure time

ranged from 0.0 years to 4.5 years, and it was also statistically longer among cases (1.6±1.4

years) than controls (0.9±1.1 years) (P<0.01). For sub-group comparisons, cases and controls

were allocated into three levels of total exposure time: 0.0 to 1.5 years for low level exposure,

1.5 to 3.0 years for medium level exposure, and 3.0 to 4.5 years for high level exposure (See

Figure 6). 25.8% of cases had a high level exposure compared to 11.6% of controls (χ2=24.9,

P < 0.00), which indicated that cases had a significantly greater percentage of high level

exposure than controls.

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Figure 6. Bar graph of percentages by three levels of total exposure time

Types of work included eight different categories, such as 297 indoor employees (31.3% of

total subjects), 16 gas-cutting workers (1.7%) and 12 planing machine operators (1.3%).

Among cases, 53 welders (27.9%), 41 assemblers (21.6%) and 16 smelters (8.4%) were three

larger types of work. Among controls, 270 indoor employees (35.5%) were the largest, 162

assemblers (21.3%) the second, and 8 planing machine operators (1.1%) the smallest. There

was statistically significant difference between cases and controls in “type of work” as a

whole (P<0.01). In order to show the difference in total exposure time among types of work,

cases and controls were put into three groups (See the previous paragraph) using three levels

of total exposure time (0.0 to 1.5 years for low level exposure, 1.5 to 3.0 years for medium

level exposure, and 3.0 to 4.5 years for high level exposure) for each type of work. The

results showed that cases with outdoor types of work usually had a medium to high level heat

exposure (See Figure 7).

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Figure 7. Bar graph of percentages by three levels of total exposure time among eight types

of work

Four categories of departments in this study were analysed, namely shipbuilding, ship-repair,

production security and indoor departments. The shipbuilding department contained 37.6% of

the total subjects, with indoor, production security and repair departments representing for

31.9%, 16.7% and 13.8% of the total, respectively. Among cases, 86 workers (45.3%) were

from the shipbuilding department, with 40 workers (21.1%) from ship-repair, 33 workers

(17.4%) from production security, and 31employees (16.3%) from indoor departments.

Among controls, employees from indoor department and workers from the shipbuilding

department accounted for 35.8% and 35.7% of the cases, respectively. There was a

statistically significant difference of the percentage composition of departments between

cases and controls (P<0.01) (See Table 3).

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56

In addition, statistical analyses showed that there was no significant difference in abnormal

ECG and hypertension between cases and controls. It was considered that heat exposure

could induce and exacerbate both heart diseases and hypertension according to the literature.

Hypertension was also reported to be associated with urolithiasis [65]. However, the

descriptive analyses suggested that abnormal ECG and hypertension might not be risk factors

of urolithiasis in this particular working population.

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Table 3. Descriptive statistics and univariate analysis of variables

Case Control P-value

M ± SD M ± SD

Age 37.8 ± 11.4 37.8 ± 11.4 0.45

Length of service (yr) 16.7 ± 11.3 15.9 ± 11.0 0.00**

Average exposure time (hr) 6.6 ±2.6 5.0 ± 3.4 0.00**

Total exposure time (yr) 1.6 ± 1.4 0.9 ± 1.1 0.00**

Sex Frequency (%) Frequency (%) 1.00

Male 158 (83.2) 632 (83.2)

Female 32 (16.8) 128 (16.8)

Type of work

0.00**

Welder 53 (27.9) 125 (16.5)

Assembler 41 (21.6) 162 (21.3)

Production security and quality inspector 33 (17.4) 126 (16.6)

Smelter 16 (8.4) 32 (4.2)

Planing machine operator 4 (2.1) 8 (1.1)

Spray painter 12 (6.3) 25 (3.3)

Gas-cutting worker 4 (2.1) 12 (1.6)

Indoor 27 (14.2) 270 (35.5)

Department

0.00**

Shipbuilding 86 (45.3) 271 (35.7)

Ship-repair 40 (21.1) 91 (12.0)

Production security 33 (17.4) 126 (16.6)

Indoor 31 (16.3) 272 (35.8)

ECG

0.66

Abnormal 39 (20.5) 146 (19.2)

Normal 151 (79.5) 614 (80.8)

BP

0.08

Abnormal 42 (23.7) 129 (17.0)

Normal 148 (77.9) 631 (83.0)

** P-value < 0.01

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4.2 Overlapping effect

When “type of work” and “department” were entered into a conditional logistic regression

model, there was an obvious overlapping effect which led to the absence of production

security department (See Table 4). The reason was that the “production security department”

provided the same information as “production security and quality inspector” when both put

into one model together. This was another reason why “type of work” and “department” were

not included in the same model.

Table 4. Overlapping effect between type of work and department

Covariates Degree of freedom OR [95% CI] P-value

Type of work 7 0.00

Welder 1 4.4 [2.0–9.4] 0.00

Assembler 1 2.6 [1.2–5.8] 0.02

Production security and quality inspector 1 3.8 [2.0–6.9] 0.00

Smelter 1 4.4 [1.7–11.2] 0.00

Planing machine operator 1 6.0 [1.4–25.6] 0.02

Spray painter 1 4.9 [1.6–14.6] 0.00

Gas-cutting worker 1 3.4 [0.9–13.4] 0.07

Department 2a 0.10

Shipbuilding 1 1.4 [0.7–2.8] 0.34

Ship-repair 1 2.1 [1.0–4.4] 0.05

a. Degree of freedom reduced because of constant or linearly dependent covariates

b. Constant or Linearly Dependent Covariates S=Stratum effect. Production security

department = Production security and quality inspector (type of work) + S.

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4.3 Association between risk factors and urolithiasis

Due to a strong correlation, it was decided that type of work and department should be

examined in two separate models. Therefore, the model using type of work was performed

for the main analysis in this section, and the model using department was run as a sensitivity

test in section 4.4.

In Step 1 of the Purposeful Selection of Covariates, four risk factors, including type of work,

total exposure time, ECG and BP, were put into bivariate analyses one at a time.

Three risk factors (except ECG) with statistical significance (P<0.25) from Step 1 were

added into an initial multivariable model (Step 2), which was statistically significant (χ2=1.0,

df=9, P<0.01). All three covariates were of statistical significance (P<0.05). Thus type of

work, total exposure time and BP were added to the new model.

In Step 3, no variable was reintroduced into the new model because no variable was

excluded in Step 2. In Step 4, ECG was reintroduced into the model, and it showed no

statistical significance itself in the model. Also, it was not considered as a confounder for the

present covariates (type of work, total exposure time and BP). Thus ECG was still excluded

from the model.

Step 5 was an effect modification step which means the check for two way interaction

between every pair of covariates in the model. No significant interaction was found in this

step. In Step 6, the final accepted model included three covariates. Their ORs, 95% CIs and

P-values are presented in Table 5.

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Table 5. Odds ratios of risk factors of urolithiasis in the conditional logistic regression model

Covariate Crude1 OR

[95%CI]

P-value

(P<0.25)

Adjusted2 OR

[95%CI]

P-value

(P<0.05)

Type of work 0.00 0.00**

Welder 6.1 [3.4–10.9] 0.00 3.7 [1.9–7.2] 0.00**

Assembler 3.6 [2.0–6.6] 0.00 2.2 [1.1–4.3] 0.03*

PSQI3 3.5 [1.9–6.3] 0.00 2.7 [1.4–3.0] 0.00**

Smelter 6.4 [2.9–13.9] 0.00 4.0 [1.8–9.2] 0.00**

PMO4 7.2 [1.9–27.4] 0.00 4.0 [0.9–16.6] 0.06

Spray Painter 6.9 [2.7–17.7] 0.00 4.4 [1.7–11.4] 0.00**

Gas-cutting worker 4.3 [1.3–14.6] 0.02 2.6 [0.7–9.1] 0.15

Indoor employee REFERENT

Total exposure time (yr) 1.7 [1.5–2.1] 0.00 1.5 [1.2–1.8] 0.00**

BP 1.5[1.0–2.2] 0.08 1.6 [1.0–2.5] 0.04*

ECG 1.1 [0.7–1.6] 0.68 N/A (not entering the final model)

** P-value < 0.01; * P-value < 0.05.

1Crude ORs were results from the bivariate analysis in Step 1.

2Adjusted ORs were results from the final multivariable model in Step 6.

3PSQI: Production security and quality inspector.

4PMO: Planing machine operator.

When adjusted for total exposure time and BP, the odds of urolithiasis for welder were 3.7

times higher than indoor employees. Similarly, the ORs of smelter, spray painter, production

security and quality inspector, and assembler were adjusted. They suggested that the odds of

smelter, welder, spray painter, production security and quality inspector, and assembler of

having urolithiasis were increased by 302%, 273%, 293%, 168% and 116% compared to

those of indoor employees (See Table 5 and Figure 8). The OR of total exposure time was 1.5,

meaning that if the total exposure time increased by one more year, the odds of having

urolithiasis would increase by 50%. The OR of BP was 1.6, which meant that if workers or

employees had hypertension, their odds of urolithiasis increased by 60% compared to those

having normal blood pressure.

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Figure 8. Odds ratios and 95% confidence intervals for seven different types of work

*PMO: planing machine operator; PSQI: production security and quality inspector; referent is

the red line represented for indoor employees.

4.4 Sensitivity test of the multivariable model

As “department” provides similar occupation information as “type of work”, “department”

was used to replace “type of work” to test the multivariable model built in the previous

process.

There were three covariates included in the model under the category of “department” (χ2

=55.05, df=5, P<0.05) (See Table 6). The adjusted ORs of total exposure time and BP

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62

changed little when adjusting for “department” instead of “type of work” in the modelling

procedure.

Table 6. Odds ratios of risk factors for urolithiasis in the conditional logistic regression

model for a sensitivity test

Covariate Crude OR

[95%CI]

P-value

(P<0.25)

Adjusted OR

[95%CI]

P-value

(P<0.05)

Department 0.00* 0.08

Shipbuilding 3.5 [2.2–5.8] 0.00* 1.9 [1.0–3.6] 0.04

Ship-repair 5.0 [2.8–9.0] 0.00* 2.5 [1.2–5.2] 0.01

Production Security 2.8 [1.6–5.0] 0.00* 2.0 [1.1–3.7] 0.03

Indoor REFERENT

Total exposure time (yr) 1.7 [1.5–2.1] 0.00 1.5 [1.2–1.9] 0.00**

BP 1.5 [1.0–2.2] 0.08 1.6 [1.0–2.5] 0.03*

ECG 1.1 [0.7–1.6] 0.68 N/A (not entering the final model)

** P-value < 0.01; * P-value < 0.05.

In conclusion, the analysis used descriptive, univariate and bivariate analyses, and a

conditional logistic regression modelling process to explore associations of risk factors with

urolithiasis. Descriptive and univariate analyses showed that cases had significantly longer

length of service, average exposure time and total exposure time than controls. Compared to

controls, cases also had a greater percentage of medium and high levels of total exposure time.

The percentages among different types of work were significantly different between cases

and controls, as were the percentages among different departments.

In the final conditional logistic regression model, results showed that the OR of urolithiasis

for total exposure time was 1.5 (95% CI: 1.2–1.8) in the multivariable model (Table 5). This

implies that if the total exposure time increased by one more year, the OR of urolithiasis

increased by 50%. Five types of work (spray painter, smelter, welder, production security and

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quality inspector, and assembler) had higher odds of urolithiasis compared with indoor

employees, which meant that workers of these five types of work were significantly more

likely to have urolithiasis. The values of adjusted ORs and 95% CIs for the workers were:

spray painter (OR=4.4, 95% CI: 1.7–11.4), smelter (OR=4.0, 95% CI: 1.8–9.2), welder

(OR=3.7, 95% CI: 1.9–7.2), production security and quality inspector (OR=2.7, 95% CI: 1.4–

3.0), and assembler (OR=2.2, 95% CI: 1.1–4.3). The OR of urolithiasis for hypertension was

1.6 (95% CI: 1.0–2.5) in the multivariable model (see Table 5). These data imply that

workers with hypertension were significantly more likely to have urolithiasis compared to

workers with normal blood pressure levels.

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CHAPTER 5: DISCUSSION AND CONCLUSION

5.1 Key findings in this study

This study demonstrated that there was a clear association between ambient heat exposure

and urolithiasis among outdoor workers in Guangzhou, China. Workers with longer lengths

of total exposure time were more likely to have urolithiasis. Workers with outdoor work were

more likely to have urolithiasis than those in other types of work. Workers with hypertension

were also more likely to have urolithiasis compared to those with normal BP levels.

Therefore, this study provides evidence that ambient heat could contribute to increasing

urolithiasis prevalence, and therefore, outdoor workers are more likely to develop urolithiasis

compared to indoor employees.

5.2 Public health implications

This study found a significant association between ambient heat exposure and urolithiasis

among shipbuilding workers in a subtropical area in China. The results have several major

implications for both the planning and implementation of public health interventions.

Firstly, health surveillance data can be an important source of reporting health outcomes (e.g.

urolithiasis) resulted from ambient heat exposure, and it can help to identify high risk

industries and occupations. This provides useful information for decision-makers to develop

intervention strategies to minimise adverse health outcomes from ambient heat exposure. For

example, to recommend training on heat-induced urolithiasis prevention, to detect the

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incidence of urolithiasis in high risk industries, and to implement governmental notification

programs if the incidence of urolithiasis continue to increase due to lacking of necessary

occupational health management performed by employers. These strategies will promote

spontaneous prevention of heat-induced urolithiasis in both outdoor and indoor workers. In a

long run, this can help to reduce the substantial financial burden to workers, industries and

health care system.

Secondly, this study suggests some characteristics for identifying the high risk types of work

in subtropical or tropical areas. For example, workers in long uniforms and full-covered

personal protective equipment (PPE) with long total exposure time to ambient heat are more

likely to have urolithiasis; occupations working with a heat source, heavy workloads and

fully-covered PPE are also at high risk; and workers with hypertension are susceptible to

urolithiasis. Therefore, after the research findings and recommendations were informed,

decision makers at a local level can use these characteristics to identify high risk groups for

implementing interventions, e.g. availability of free water supplies, reasonable water breaks

and working time schedules, and decreased workloads during hot days.

Thirdly, the findings of this study show that an annual health check program should include a

urolithiasis examination for outdoor working populations. This study was based on health

surveillance data collected from a shipbuilding company in Guangzhou, China. However,

urolithiasis-relevant medical examinations (e.g. kidney ultrasonography and abdominal X-ray)

were not an essential item for the health check program of shipbuilding workers according to

the official health surveillance requirements in China [66]. The shipbuilding company in this

study was one of a few companies that had their workers undertake regular health checks

with a urolithiasis examination, and it provided important medical information on heat-

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induced urolithiasis among outdoor workers. Hence, it is necessary to advocate the

incorporation of a urolithiasis examination in the health check program for outdoor workers.

More attention should be paid to preventing adverse health outcomes from long-term ambient

heat exposure.

5.3 Recommendations

From the findings of this study, preventative intervention should be taken to minimise the

adverse impacts of ambient heat exposure on urolithiasis among outdoor workers. There are

some practical recommendations on workplace and personal interventions and they are listed

as the follows.

Firstly, training is necessary to educate field supervisors and outdoor workers to recognize,

reduce and prevent ambient heat impacts on urolithiasis, especially for those at higher risk.

Some knowledge and skills are important for protecting outdoor workers from heat impacts

(e.g. effectively replenishing water such as drinking small amounts of water frequently before

they feel thirsty [79], avoiding working under the sun during the hottest period of hot days,

organising water breaks for rest and rehydration in cool areas and reducing workloads during

hot days).

Secondly, reducing workloads in hot months is an important measure for urolithiasis

prevention. According to “Threshold Wet Bulb Globe Temperature (WBGT) Levels”, the

heavier the workloads are, the lower the threshold levels should be [80, 81]. This means that

workers are more vulnerable to temperature increases when they have heavier workloads.

Because heavier workloads require more energy, such work usually causes an increase in

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body temperature in a short period of time. This can stimulate the thermoregulation system of

the body to balance the core body temperature through elevated skin blood flow, sweating

and respiration. Thus heavy workloads will increase water loss and aggravate dehydration

status facilitating urolithiasis [79]. Workers with heavier physical work under ambient heat

were more likely to have urolithiasis. Hence, it is necessary to reduce workloads in hot

months. One method of achieving this is to shorten work time. This can be integrated with

working time schedule adjustment in hot months, which includes avoiding working during

the hottest period of the day (e.g. 1 to 4 pm) and establishing work/rest schedules appropriate

for the current heat indices [79]. An appropriate work/rest regimen can also be beneficial. For

example, Attia et al. [82] performed a field study on heat stress and recovery welders and

found that the optimization work/rest regimen was work (2h)/rest (2h) because welders had

almost full recovery from heat stress, while welders of work (2h)/rest (1h) or work (1h)/rest

(1h) did not reach complete recovery during resting period.

Thirdly, it is necessary to encourage appropriate fluid intake [83, 84], because adequate

hydration is a primary element in preventing urolithiasis [83, 85]. This includes the proper

kinds of and the appropriate amount of liquid consumption. Evidence has shown that if

acclimatisation is good and sufficient liquids are consumed, the effect of heat on urolithiasis

is minimal [86]. However, the proper amount of liquid intake is yet to be determined. Since

normal urine is supersaturated with various stone forming salts, it is considered that urine

contains potent inhibitors for controlling crystal formation, aggregation and subsequent stone

formation [70]. Urolithiasis formation is usually determined by how much the urine is

supersaturated with respect to calcium oxalate and calcium phosphate on the one hand, and

the activity of various inhibitors on the other [71]. It is possible that too much fluid intake

will reduce the inhibitory activity sufficiently to negate the beneficial effect of reduced

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saturation. This was recognised in an epidemiological study performed by Tucak et al. [41]

which reported that people consuming less than 2 litres of liquid every day had the highest

incidence of urolithiasis, people with more than 2 litres was the second, and people with

around 2 litres had the lowest incidence of urolithiasis. In terms of the general population, 2

litres of liquid intake every day is recommended. However, for the working population under

ambient heat, it is better to measure their hydration status as they lose more water through

perspiration, and their liquid intake will therefore be greater than that of the general

population.

In order to adequately replenish water loss and encourage appropriate amount of fluid intake

for heat-exposed workers, hydration status needs to be measured. According to the

experience from Australian mining industry, measurement of urine gravity is a practical way

for identifying hydration status [87, 88]. It can be easily performed before work and after

work with the Hydrate 1TM

System [89] or with specific gravity test strips [90]. This

measurement indicates whether workers have condensed urine or not, which suggests the

needs to take more fluid or not. This measurement can also provide information to

supervisors on managing the fluid supply and the frequency of intermittent water breaks [79].

Specific gravity of urine measurement has been implemented in the mining industry for a

long period of time, and has successfully prevented miners exposed to underground heat from

heat stroke and urolithiasis in Australia [87, 88].

Fourthly, access to shade or cooling areas such as air-conditioned rooms or shaded areas with

fans is a common but important method [79] for preventing the core body temperature from

reaching over-heating status. The human body must maintain a core temperature between

36.0–37.2 °C to keep functioning properly [91], and if the core body temperature increases,

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the body will deal with heat stress through thermoregulation, which includes elevated skin

blood flow, sweating and respiration. When water loss generated by thermoregulation is not

compensated in time, dehydration can lead to acute effects such as exhaustion and even heat

stroke, and if the human body sweats over an extended period, it can result in chronic

dehydration and a decrease in the volume of urine. These are important risk factors for

urolithiasis. Thus, providing access to shade or cooling areas can also be an important

interventions for preventing urolithiasis by minimising dehydration.

Moreover, there are recommendations for urolithiasis prevention at an individual level, which

can be supplemented through workplace training programs. Poor personal hygiene habits can

fail to protect them from getting unnecessary chemicals or heavy metals of renal toxicity into

their body. For example, it may increase the potential cadmium absorption if spray painters

do not change their clothes and make sure their hands and mouths free of cadmium-

containing paint pigments before drinking water or having meals at the workplace. Besides,

individual recommendations should include suggestions on an increased dietary intake of

calcium. Lower calcium intake levels can stimulate 25(OH)D mediated absorption and

urinary excretion of calcium, while increased dietary intake of calcium is not associated with

a greater prevalence of urolithiasis [92, 93]. Recommendations should also contain

suggestions to increase appropriate levels and kinds of fluid consumption. A low urine

volume was considered to be an important risk factor for calcium stone formation, so a high

fluid intake may be beneficial in the management of urolithiasis. Distilled water is

recommended to be consumed, but one might anticipate adverse effects of various kinds of

other fluids (e.g. beer, mineral water, and soft drinks). Beer may contain considerable

amounts of calcium, oxalate and guanosine, which is metabolized almost completely to uric

acid [94-96]. Bicarbonate alkaline water and mineral water should also be avoided because

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drinking bicarbonate alkaline water with a high content of calcium leads to an increase in the

urinary calcium level by 50% [97]. It was found that replacing one litre of the usual fluid

intake with mineral water elevated the urinary calcium for normal subjects as well as

urolithiasis cases [98, 99]. The high oxalate content of soft drinks (e.g. apple juice and

grapefruit juice) are common examples for adverse effects [100]. Moreover,

recommendations should cover the promotion of healthy behaviours that will benefit

urolithiasis prevention, e.g. abatement or cessation of smoking, lower consumption of animal

protein and fat, and higher consumption of vegetables [101, 102].

5.4 Alternative explanations

5.4.1 Chance

In this study, the association between ambient heat exposure and urolithiasis was examined,

taking into account total exposure time, type of work, ECG and BP. These findings are

unlikely to be explained by chance because of the following reasons:

Firstly, all the statistically significant tests were driven by the hypotheses. All available data

were analysed and a whole spectrum of research findings was presented.

Secondly, there is consistent evidence that urolithiasis is associated with ambient heat

exposure among outdoor workers. Such evidence was not only observed for total heat

exposure time, but also through the association with different types of work with different

workloads and PPE.

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Thirdly, rigorous statistical approaches were used to examine the association between

ambient heat exposure and urolithiasis. The multivariable logistic regression models using

“types of work” or “departments” produced similar results, which strengthened the validity of

the research findings.

5.4.2 Bias

Information bias could occur in the process of data collection, although the health

surveillance data from the affiliated hospital of the company was considered reliable as they

were from original hard copies of health check files in this study. Firstly, measurement error

in urolithiasis diagnosis could be a source of information bias. Kidney ultrasonography

results from different health exam years were used as the main medical evidence for

urolithiasis diagnosis in this study. The kidney ultrasonography results were measured in the

same hospital but from different years (from 2003 to 2010). This means that there is a

possibility of diagnostic bias because the ultrasonic tests were conducted by different

practitioners using a variety of somascopes. Secondly, bias may have occurred from the strict

selection criteria for cases, which may have excluded some potential correct cases. For

example, three cases with less than three years of employment were not selected for analysis,

because an estimated time for generating urolithiasis among the general population was

longer than three years [68]. Although these cases could still be associated with ambient heat

exposure at work due to individual differences, the influence from the three excluded cases is

impossible to be significant when compared to the other 190 cases. Therefore, information

bias of such kind is unlikely to change the results remarkably. Thirdly, information bias

might also affect calculation for total exposure time and the estimation of average exposure

time, because both of these indices were not from actual measurement but based on OHSOs‟

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observation and experience. However, they were a useful estimation when the actual

measurement was difficult to carry out for a chronic disease which required a long period of

follow-up observation, and for a project with unidentifiable secondary data which were not

able to find those exact subjects for further information on previous ambient heat exposure.

5.5 Comparison with other studies

5.5.1 Previous studies on ambient heat and urolithiasis

Urolithiasis constitutes a major health problem worldwide and many studies report the role of

heat as a significant risk factor for urolithiasis [12]. These studies were all based on the

hypothesized mechanism that heat induced urolithiasis is attributed to water loss from

sweating. The decrease of extracellular fluid causes an increase in serum osmolality which

increased the vasopressin, leading to low urinary volume and concentrated urine.

Concentrated urine contains higher levels of relatively insoluble salts, e.g. calcium oxalate,

and these salts precipitate out of solution when their upper limits of solubility are exceeded,

forming urolithiasis. Sunlight exposure is an alternative explanation for the association

between heat and urolithiasis, as it has been related to hypercalciuria [24]. The association

between heat exposure and urolithiasis has been examined from different aspects: some

observed the association over geographical variation in epidemiological studies [12], some

investigated the association on temporal variation in the same geographic area by season

[103], while the others reported the association with general analyses [83].

Geographical variation in the prevalence of urolithiasis in previous national studies has been

observed. Sourcie et al. [12] mapped out the prevalence of urolithiasis based on nationwide

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survey data in the United States, and found that the trend of increasing prevalence was from

North to South and from West to East. The authors also found a higher risk in the hottest and

sunniest locations. Similar results were found in Australia [104], Iran [75], and Turkey [105].

Studies have shown that the role of heat in the pathogenesis of urolithiasis has seasonal

variation. Robertson et al. [103] performed one of the first studies to investigate the seasonal

variation on the incidence of urolithiasis in Leeds, Great Britain. They analysed 24-hour urine

samples and found that the values of calcium and oxalate were significantly higher in summer,

and their changes were correlated with heat and hours of sunlight. Studies have also been

performed in many other countries on the seasonal variation of urolithiasis in regards to

temperature difference, including Finland [105], Kuwait [106], Iraq [107], Saudi Arabia

[108], Iran [109], Japan [110], Taiwan [79], the United States [111] and Italy [112], with all

reporting similar results.

Temporal changes over time in the same geographical area were also observed. For example,

Stamatelou et al. [102] performed a study in the United States which compared the

prevalence of urolithiasis between 1988–1994 and 1976–1980. The prevalence of urolithiasis

increased for both males and females when temperature increased. Similar results were also

found in the United Kingdom [113], Italy [43, 97], Japan [104], and Germany [83].

Some studies have examined the association between occupational heat exposure and

urolithiasis. Pierce et al. [16] reported in 1945 that the incidence of urolithiasis among

American troops deployed in desert areas was two-fold higher than those in mountainous

areas. Later, Blacklock et al. examined the British Royal Navy on the incidence of

urolithiasis among different occupations, and found that engineers in the hot engine room had

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a higher incidence of urolithiasis [17]. Another study was conducted with British troops who

were transported from the United Kingdom to the Persian Gulf, and found that the group

transported in summer had a significantly higher level of urine calcium excretion than those

transported in winter. This had been attributed to longer hours of sunlight exposure and

higher temperatures [24]. A study in Italy and a study in Brazil found that workers exposed to

heat from glass production or furnaces in the steel plant had a much higher risk of urolithiasis

than those who were not exposed to heat [20, 21]. Pin et al. [26] reported that some outdoor

occupations had a higher prevalence of urolithiasis than indoor occupations in Singapore.

The above studies have provided a body of literature supporting the potential contribution of

heat to an increased prevalence of urolithiasis. Although studies were from different countries

demonstrated the possible role of heat in the development of urolithiasis, the quantified

association of heat exposure with urolithiasis in specific groups or occupations remains

unclear. In order to explore the quantified association with different occupations, this study

focused on outdoor workers in a shipbuilding company. The comparisons with previous

studies are indicated in the following section.

5.5.2 General comparisons of study designs and results

Impacts of ambient heat exposures were combined with effects of the sunlight in many

studies [16, 18, 19, 24, 26]. For example, the earliest study on the association between

ambient heat exposure and urolithiasis stated that American troops stationed in a “desert area”

had two-fold higher prevalence of urolithiasis than those in mountainous areas [16]. However,

this study did not provide an exact prevalence or any statistical analyses. It did not clearly

verify the association between the prevalence or incidence of American troops in desert areas

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and those in mountainous areas, nor the contribution of ambient heat or sunlight. In another

study on British troops, the group deployed from the United Kingdom to the Persian Gulf in

summer had a higher risk of hypercalciuria while those in winter did not; the results were

considered to be associated with longer sunlight exposure and higher temperature [24]. The

investigators in this study examined the association between the increased exposure to

sunlight and hypercalciuria. In a cross-sectional study performed by Better et al. [18] in Israel,

the risk of urolithiasis in lifeguards was ten-fold greater than that in the general population,

and metabolic changes in blood and urine were examined for evidence of urolithiasis

formation; again it was thought the increase should be due to both the intensive sunlight

exposure and heat on an almost completely bare body. Thus, the independent effect of

sunlight and ambient heat had not been thoroughly examined.

Sunlight exposure influences the serum concentration of 25(OH)D, which facilitates the

process of urolithiasis formation by inducing hypercalciuria [24]. Studies in Turkey and

Jordan showed a strong relationship with clothing and serum 25(OH)D, which decreased for

women in western clothing compared to those wearing the traditional hijab or completely

veiled in niqab [111, 114]. Thus skin covered by clothes played a predominant role in

determining sunlight-induced 25(OH)D increase which was associated with urolithiasis

formation. In comparison, the impact from sunlight exposure on workers in this study had

been minimised. As shipbuilding workers in this study had to be in long uniforms and put on

PPE (e.g. safety helmet, mask, gloves and safety shoes) on workdays due to occupational

health and safety purpose, most of their skin was protected from exposure to sunlight. This

minimised the impact from direct sun exposure on urolithiasis through increasing 25(OH)D

level, so this study was able to analyse the independent association of ambient heat exposure

and urolithiasis.

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The causal relationship between occupational ambient heat exposure and urolithiasis has been

described in previous literature in general terms only. For instance, a cross-sectional study

conducted in Singapore reported higher prevalence of urolithiasis in outdoor workers

(including quarry drilling and crusher workers, quarry truck and loader drivers and postal

deliverymen) than indoor workers based on a questionnaire methodology [26]. The study

only controlled for social class as a confounding factor and used a simple descriptive

statistical method for analysing the differences in prevalence between outdoor workers and

indoor workers. The authors stated that urolithiasis resulted from prolonged physical activity

under extreme tropical heat with low fluid intake. However, they failed to account for several

important confounders. In order to verify the association between occupational ambient heat

exposure and urolithiasis, careful consideration of other risk factors is required.

In this study, a matched 1:4 case-control design was used, and age and sex were used as two

matching criteria. More reliable data from medical health checks were collected instead of

questionnaires. For statistical analyses, a conditional logistic regression model was used for

analysing the association between heat exposure and urolithiasis. The risk factors considered

in this study included length of ambient heat exposure, different types of work with various

ambient heat exposure levels, and health status relevant to heat exposure such as heart

diseases and hypertension. The results of this study were consistent with those of previous

research.

5.5.3 Association between total exposure time and urolithiasis

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Several studies have investigated the association between length of service and urolithiasis,

but only two studies found a statistically significant difference in length of service between

heat-exposed and non-heat-exposed groups [18, 20, 21, 26]. Pin et al. [26] only provided the

average working time per week for both outdoor workers and indoor employees, and found a

statistical significant association between outdoor workers and urolithiasis. However, they

did not quantify ambient heat exposure time for describing this association. Better et al. [18]

performed a cross-sectional study among lifeguards in Israel, and reported on the average

length of service among cases which was significantly longer than that of the general

population. Their results were limited because average working time and length of service

alone were not able to provide all the relevant heat exposure information solely. In order to

reflect the cumulative amount of ambient heat exposure, this study used total exposure time

(average exposure time multiplied by adjusted length of service) for assessing the ambient

heat exposure for workers and employees in the shipbuilding company. Total exposure time

could be a good indicator because it contains information derived from both average

exposure time and length of service. This study showed that total exposure time was an

important risk factor for urolithiasis formation among subjects (See Table 5).

5.5.4 Association between the type of work and urolithiasis

Previous studies indicated that occupations in hot environments had an increased risk of

urolithiasis [17, 18, 20, 21, 26]. However, they often combined the effects of ambient heat

exposure and sunlight exposure together. By contrast, this study minimised the effect of

sunlight exposure on urolithiasis in the model, as was stated in 5.3.2. Hence, it was possible

for us to analyse the independent effect of ambient heat exposure on urolithiasis.

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In general, heat stress on workers can be affected by climatic and non-climatic factors which

include workloads, clothing and high temperature operations, etc. [108, 115, 116]. For

outdoor workers in this study, the main climatic factor was ambient heat exposure during hot

months and this was determined by the climate itself. However, non-climatic factors varied

according to different types of work. Threshold WBGT is used to measure the highest

tolerable limit for health and safety of high temperature work.

For example, if workers undertake heavy work, their threshold WBGT should be reduced by

4 °C given the threshold level of 30 °C for light work when male workers normally clothed,

acclimatized, physically fit and in good health [80] (See Table 7). Meanwhile, this threshold

WBGT will be modified according to different conditions. If workers undertake heavy work

wearing impermeable full-length coats, it is recommended that threshold WBGT levels

should be reduced by another 4 °C [80] (See Table 8). In this study, spray painters were in

this situation because they were allocated to the heavy workload category by OHSOs and had

to wear impermeable full-length coats and other PPE including full face mask respirators,

chemical protective gloves and safety shoes. The possible explanations were that spray

painters had to hold high pressure spray guns to spray hulls involving stretching, bending and

twisting of their bodies on unshaded scaffolds [115], which required quite big amount of

calories that met the criterion of heavy work (See Table 7); and spray painters had to wear

impermeable PPE to avoid the exposure of high speed paint pigments and aerosols from

spraying [97]. Thus even under the same ambient temperatures in hot months, ambient heat

stress might impact on spray painters more severely than other types of work (OR=4.4,

95% CI: 1.7–11.4).

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Table 7. Threshold WBGT levels for different workloads among men normally clothed,

acclimatized, physically fit and in good health

Workload WBGT, °C

Light work (less than 200 kcal/hr) 30

Moderate work (201–300 kcal/hr) 28

Heavy work (301–400 kcal/hr) 26

Very heavy work (above 400 kcal/hr) 25

Source: Yousef, M., et al. [80]

Table 8. Modification of threshold WBGT level by different conditions

Condition Modification of WBGT

Unacclimatized Subtract 2 °C

Unfit Subtract 2 °C

Obese Subtract 1–2 °C

Old age Subtract 1–2 °C

Females Subtract 1 °C

Clothing

shorts or seminude Add 2 °C

impermeable jackets Subtract 2 °C

impermeable full-length coats Subtract 4 °C

impermeable completely enclosed suits Subtract 5 °C

Increased air velocity above 1.5 mps, as long as air

temperature is below 35

Add 2 °C

Source: Yousef, M., et al. [80]

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Working with exogenous heat generated by equipment or tools is another non-climatic factor.

Atan et al. [21] reported that steel workers exposed to heat from furnaces (ranging from 40–

1500 °C) had higher prevalence of urolithiasis than those not exposed. In this study, smelter

workers who worked beside furnaces also had a higher risk of urolithiasis (OR=4.0, 95% CI:

1.8–9.2). Moreover, the risk of urolithiasis was also high among welders (OR=3.7, 95% CI:

1.9–7.2) who had to face exogenous heat stress of 8.33 °C (15 °F) when welding [93], with

estimated heavy workloads by OHSOs and relevant PPE, e.g. full-length coats, welding mask

and welding gloves (See Table 10).

The occupations of assembler and production security and quality inspector are generally

regarded as to be of lower risk for urolithiasis, and few previous studies had studied these two

groups. However, this study found that there was a mild but statistically significant higher

risk of urolithiasis for assemblers (OR=2.2, 95% CI: 1.1–4.3) and production security and

quality inspectors (OR=2.7, 95% CI: 1.4–3.0), with common PPE and workloads estimated to

be heavy and moderate, respectively (See Table 10). These higher risks of urolithiasis

suggested that ambient heat exposure in these working groups could currently be

underestimated. These workers should take care to consume adequate water and take regular

water breaks for health protection purposes.

Two other types of work, planing machine operator and gas-cutting worker, showed no

increased risk of urolithiasis (See Table 5). The main task for planing machine operators and

gas-cutting workers is to groove metal for welding and to perform metal cutting with an

oxyacetylene cutting torch, respectively. The results were reasonable because their workloads

were regarded as light; and only 5 hours of their work time (as estimated by OHSOs) were

occupied by physical and strenuous work, which would also increase the threshold WBGT

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limits (See Table 9). Although the work environment for planing machine operators and gas-

cutting workers was shaded in concrete work sheds, these workers were still exposed to

ambient heat as no air-conditioners were installed. However, their work environment is

regarded as much more comfortable than many other types of work (e.g. spray painters,

welders and assemblers) operating outdoors or inside closed steel cabins heated by the sun on

hot days.

Table 9. Threshold WBGT limits

Work-rest regimen

Workload

Light Moderate Heavy

Continuous work 30.0 26.7 25.0

75% work+25% rest; each hour 30.6 28.0 25.9

50% work+50% rest; each hour 31.4 29.4 27.9

25% work+75% rest; each hour 32.2 31.1 30.0

Source: ACGIH (1996) [81]

Literature also suggested some potential factors that might pose the risk of urolithiasis to

certain types of workers besides ambient heat. For welders, cadmium exposure may be a

possible reason for an increasing risk of urolithiasis. Earlier studies reported that workers

exposed to cadmium had a higher prevalence of urolithiasis [117, 118]. Trevisan et al. [119]

published a clinical case report of urolithiasis on a welder who was exposed to cadmium at

work. A recent study performed by Ding et al. [120] in China reported that 6 out of 103

railway welders had urine cadmium levels exceed the Chinese reference value and 17% of

samples exceed the threshold limit value of the concentration of airborne cadmium. However,

cadmium had not been detected in the air samples of welding fumes at workplace and

shipbuilding material including the hull steel and welding rods (wires) in the 2010 technical

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83

report of the company carried out by an certified organization providing service of

construction project occupational hazard evaluations (Guangdong Province Hospital for

Occupational Disease Prevention and Treatment, unpublished data). Thus cadmium exposure

should not be the main reason for higher risk of urolithiasis among welders in this study.

For spray painters, paint and solvent exposure may be a possible causal factor for urolithiasis

formation. Laerum et al. [121] reported that railroad shopmen exposed to oxalic acid which

was used in a repainting and cleaning process for railroad cars was associated with

urolithiasis. Vitayavirasuk et al. [122] reported that spray painters working in automobile

body repair shops had significantly higher urine cadmium level than the matched general

population because cadmium was components of paint pigments. Increased cadmium level

was a risk factor for urolithiasis [94, 118]. However, Cadmium-containing paints are not

widely used any more in many countries including China. Meanwhile, spray painters in this

study wore full face mask respirators, impermeable full-length coats, chemical protective

gloves and safety shoes that should have been able to protect them from severe exposure to

paint and relevant solvents during the ship-repair process, which was much better than the

situations that railroad shopmen exposed to oxalic acid without efficient PPE and spray

painters with aerosol-removing respirators reported by Laerum et al. [121] and Vitayavirasuk

et al. [122]. Thus, paint and solvent exposure should not be the main reason for high

prevalence of urolithiasis among spray painters.

In this study, five types of work (i.e. spray painter, welders, assemblers and smelter,

production security and quality inspector) had a higher risk of urolithiasis than indoor

employees. These are the types of work with long impermeable suits and fully-covered PPE,

moderate to heavy workloads under ambient heat exposure, and/or working with extra heat

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84

from equipment or tools (See Table 10). The results of this study indicate that these types of

work may be more susceptible to urolithiasis, and require more attention in regards to

preventative care.

Table 10. Non-climate factors impacting on heat stress of different types of work and

relevant odds ratios of urolithiasis

Type of work OR

Non-climate factors

Clothing Workloads Heat source

Spray painter 4.4

Impermeable full-length coats, full face mask

respirator, chemical protective gloves , and

safety shoes

Heavy –

Welder 3.7

Full-length coats, welding mask, welding

gloves, safety helmet, and safety shoes

Heavy

Welding

machine

Assembler 2.2

Full-length coats, gloves, safety helmet, and

safety shoes

Heavy –

Production

security and

quality inspector

2.7

Full-length coats, safety helmet, and safety

shoes

Moderate –

Smelter 4.0

Impermeable full-length coats, smelter helmet,

smelter gloves, and safety shoes

Heavy Furnace

Planing machine

operator

– Full-length coats, safety helmet, and safety

shoes

Light –

Gas-cutting

workers

– Full-length coats, safety helmet, and safety

shoes

Light

Gas-cutting

machine

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85

5.5.5 Association between hypertension and urolithiasis

Evidence has shown that workers exposed to prolonged heat are at high risk of hypertension

[123, 124]. People with severe hypertension are not allowed to be recruited into heat exposed

occupations in many countries, including China. Those hypertensive subjects in this study

were more likely to develop hypertension after recruitment.

An eight-year follow-up cohort study on workers from the Olivetti factory performed by

Cappuccio et al. [125] reported that hypertension was a predictor for urolithiasis. This was

consistent with the finding in this study. It was demonstrated that people with hypertension

caused calcium homeostasis alteration which induced urolithiasis formation [51, 125-128].

This was the possible mechanism for explaining the result found in this study that workers

with hypertension were more likely to have urolithiasis. Outdoor heat exposure might

increase the risk of hypertension and urolithiasis, and hypertension could also increase the

risk of urolithiasis.

The results of this study indicate that outdoor workers had higher risk of urolithiasis than

indoor workers and so did workers with longer total exposure time than those with shorter

total heat exposure time. More attention should be paid to minimise the impact of ambient

heat exposure on urolithiasis, and to develop preventative strategies to protect outdoor

workers from the potential effects of climate change.

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86

5.6 Strengths and limitations

This study has five major strengths. Firstly, to our knowledge, it was the first case-control

study investigating the association between ambient heat exposure and urolithiasis between

shipbuilding workers and employees. Secondly, the datasets used in this study are quite

comprehensive with less than 5% missing values of health surveillance data. Thirdly, the data

were quite reliable as they were collected from the affiliated hospital of the company by GIHI

and derived from regular health surveillance. Fourthly, the study was able to examine the

independent effect of ambient heat exposure on urolithiasis after the confounding effects of

sunlight were minimised. Finally, this study controlled for most well-known confounding

factors, including age, sex, length of service (longer than three years), diet (at least two meals

per day were provided by the company), birth places (all of them were from Guangdong

Province) and heat exposure-related health status (hypertension and heart disease).

There are also several limitations in this study. Firstly, this study did not have information on

family history [40], obesity [129], social class [51], metabolic diseases [68], smoking and

drinking behaviours [94, 95, 130], which have been related to urolithiasis according to the

literature. Secondly, records for water drinking behaviour [65] of workers and employees

were not available because this study was mainly based on secondary health surveillance data.

Thirdly, the control selection process was not completely random, because health

surveillance files containing more information were prioritised, particular when matching by

same sex and age. However, after strictly matched 4 controls for 1 case by sex and age, there

were not a lot of choices for each set especially for male controls over 45 years old and

female controls of all age. Thus the control selection process should not significantly

influence the results. Fourthly, this study did not deal with the potential false positive results

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87

generated from the ultrasound specificity of 74% for urolithiasis screening because of the

time limit for a master‟s thesis. However, subjects with abnormal ultrasonography results in

the health checks would be required to re-examine by soma scopes for ensuring the validity

of the results and the re-examine results would also be attached to the health check files (as

mentioned by OHSOs). Not all cases were noticed that they were with the re-examine results

attached, but false positive results were rare according to the attached re-examine results in

the collected health surveillance data. So the potential positive results were considered that

they should not consist of a big percentage that generated important influence. Fifthly, this

study was lacking of actual heat exposure measurements due to mainly being based on

historical secondary data. However, according to literature, there were mainly two kinds of

occupational hazard exposure associated with kidney stones, which included heat exposure

and cadmium exposure. Potential cadmium exposure should not be the key risk factor for

outdoor workers in this study, and this has been discussed in Section 5.5.4. Ambient heat can

be interpreted to be the main key risk factor for outdoor workers. In addition, the movement

of workers between different types of work was not particularly controlled but it was really

rare for technical workers moving frequently from one certified type of work to other types as

shown in the data collected in this study, and in actual practice. The interpretation of the

findings in this study still should be treated with caution and further studies are necessary to

confirm our findings. A summary of the strengths and limitations of this study can be found

in Table 11.

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88

Table 11. Summary of strengths and limitations of this study

Order Strengths Limitations

1

The first case-control study on the association

between occupational heat exposure and

urolithiasis

There was no information on family history,

obesity, social class, metabolic diseases, smoking

and drinking behaviours

2 Missing values were less than 5%

Did not deal with the potential false positive

results due to the time limit

3 Based on the actual health check data

The control selection process was not completely

random

4

Examined the independent health impact from

heat

There was no information on water drinking

behaviours

5 Controlled for most of the confounding factors

There was lacking of actual heat exposure

measurements

6

Did not control movement between different

types of work

5.7 Directions for future research

This study used a 1:4 matched case-control study to examine the association between ambient

heat exposure and urolithiasis for 950 workers and employees in a big shipbuilding company

in China. Results showed that ambient heat exposure increased the risk of urolithiasis. In the

context of climate change, global warming will probably exacerbate the impacts of ambient

heat on urolithiasis. Thus, it is necessary to conduct further research in order to improve the

understanding of this relationship.

Firstly, improved data collection should be carried out. In this study, some potential

confounders such as family history of urolithiasis, social class and urine volume of workers

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89

and indoor employees were not available. It has been shown that an established personal or

family history of urolithiasis can increase the risk of urolithiasis by 50% [131]. Also, a low

urine volume is an important risk factor for urolithiasis in temperate climates [132]. Future

researchers can use first-hand data collection approaches for additional details of individual

information (e.g. family history, social class and metabolic diseases) through interviews or

questionnaires undertaken of workers.

Secondly, some risk factors could be better measured and observed. WBGT is a commonly

used index for the evaluation of a heat stress at threshold limits [81], and it should be set in

parallel to health check years for representing ambient temperature. The WBGT is a weighted

average of the three sensors on an area heat stress monitor: natural wet bulb temperatures

(WB), globe temperature (GT), and air temperature (dry bulb temperature, DBT). The

formula for outdoor measurements is WBGT=0.7WB + 0.2GT + 0.1DBT. This study was

based on secondary data collection, and it collected records of temperature from the official

meteorological bureau and records of health outcomes from the studied company. In future

research, ambient temperature for each workplace could also be measured by WBGT.

Similarly, important individual characteristics such as water consumption behaviour could

also be observed and recorded. Exposure time could be recorded by researchers‟ observation

or through collection of modified attendance sheets with self-reported ambient heat exposure.

Moreover, a stronger causal inference study design (e.g. a cohort study) could be employed to

evaluate the association between ambient heat exposure and urolithiasis. In this study, the

average exposure time (the main exposure index) was estimated by OHSOs, but whether the

OHSOs‟ estimations were precise enough to estimate the actual exposure still needs to be

confirmed in future studies. In a cohort study, average exposure time can be directly recorded,

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90

allowing health outcomes to be prospectively measured. A cost-benefit analysis of

preventative interventions on high risk groups could also be performed.

5.8 Conclusions

This study examined the relationship between ambient heat exposure and urolithiasis among

shipbuilding workers and indoor employees in Guangzhou, China. A conditional logistic

regression model was implemented in describing the odds ratios of various risk factors (e.g.

different types of work, total exposure time and hypertension). The study found that

shipbuilding workers with longer total exposure time, hypertension, and of certain types of

work including spray painter, smelter, welder, production security and quality inspector and

assembler were at higher risk of urolithiasis. Four of the above five occupations worked

mainly outdoors except for smelters with furnaces indoors. There were several possible

reasons for why these types of work may be impacted by ambient heat stress more than others.

These included heavier workloads, fully-covered PPE (for spray painters and welders), and

working with exogenous source of heat (for welders).

Findings in this study may have important public health implications in the control and

prevention of urolithiasis associated with ambient heat exposure among outdoor working

populations. These findings provide information for decision-makers to prioritise potential

industries similar to shipbuilding affected by ambient heat for public health interventions, and

support practical recommendations that could be incorporated into relevant industrial

regulations.

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91

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dietary calcium, oxalate, and medication exposures. American Journal of

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environments: a review. International Archives of Occupational and Environmental

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13(5): p. 361-371.

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APPENDIX 1: Tables of Results for Statistical Analyses

The multivariable modelling process with conditional logistic regression model

The multivariable modelling process (excluding department)

Step 1. Bivariate analysis (P<0.25*)

1. Type of work

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

556.7 51.8 7 0.00 54.9 7 0.00 54.9 7 0.00

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

Covariate P OR 95%CI

Type of work 0.00*

Welder 0.00* 6.1 (3.4, 10.9)

Assembler 0.00* 3.7 (2.0, 6.6)

Production security and

quality inspector

0.00* 3.5 (1.9, 6.4)

Smelter 0.00* 6.4 (2.9, 13.9)

Planing machine

operator

0.00* 7.2 (1.9, 27.4)

Spray painter 0.00* 6.9 (2.7, 17.7)

Gas-cutting worker 0.02* 4.3 (1.3, 14.6)

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2. Total exposure time

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

567.0 46.0 1 0.00* 44.6 1 0.00 44.6 1 0.00

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

Covariate P OR 95.0% CI

Total exposure time (yr) 0.00* 1.7 (1.5, 2.1)

3. Electrocardiogram

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

611.4 0.2 1 0.68 0.2 1 0.68 0.2 1 0.68

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

Covariate P OR 95.0% CI

Electrocardiogram 0.68 1.1 (0.7, 1.6)

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4. Blood pressure

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

608.6 3.1 1 0.08 3.0 1 0.08 3.0 1 0.08

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

Covariate P OR 95.0% CI

Blood Pressure 0.08* 1.5 (0.9, 2.2)

Step 2.An initial multivariable model(P<0.05*)

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

538.9 71.0 9 0.00* 72.7 9 0.00 72.7 9 0.00

a. Beginning Block Number 1. Method = Enter

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Variables in the Equation

Covariate P OR 95.0% CI

Type Of Work 0.00*

Welder 0.00* 3.7 (1.9, 7.2)

Assembler 0.03 2.2 (1.1, 4.3)

Production security and quality

inspector

0.00* 2.7 (1.4, 5.0)

Smelter 0.00* 4.0 (1.8, 9.2)

Planing machine operator 0.06 3.9 (0.9, 16.6)

Spray painter 0.00* 4.4 (1.7, 11.4)

Gas-cutting worker 0.15 2.6 (0.7, 9.1)

Total exposure time (yr) 0.00* 1.5 (1.2, 1.8)

BP 0.04* 1.6 (1.0, 2.5)

Step 3. Reintroduce variables excluded from the initial multivariable model

There is no variable excluded from the initial multivariable model.

Step4. Reintroduce variables excluded from the bivariate analysis

Reintroduce ECG (not a confounder)

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

538.9 71.0 10 0.00 72.7 10 0.00 72.7 10 0.00

a. Beginning Block Number 1. Method = Enter

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111

Variables in the Equation

Covariate P OR 95.0% CI

Type Of Work 0.00

Welder 0.00 3.7 (1.9, 7.2)

Assembler 0.03 2.2 (1.1, 4.3 )

Production security and quality

inspector

0.00 2.7 (1.5, 5.0)

Smelter 0.00 4.0 (1.8, 9.2)

Planing machine operator 0.06 3.9 (0.9, 16.6)

Spray painter 0.00 4.4 (1.7, 11.5)

Gas-cutting worker 0.14 2.6 (0.7, 9.1)

Total exposure time (yr) 0.00 1.5 (1.2, 1.8)

BP 0.04 1.6 (1.0, 2.6)

ECG 0.93 1.0 (0.7, 1.6)

Step 5. Interaction checking

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

520.3 91.2 24 0.00 91.3 24 0.00 91.3 24 0.00

a. Beginning Block Number 1. Method = Enter

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112

Variables in the Equation

Covariate P OR 95.0% CI

Type Of Work 0.10

Welder 0.25 1.7 (0.7, 4.0)

Assembler 0.89 0.9 (0.4, 2.3)

Production security and quality

inspector

0.18 1.9 (0.8, 4.7)

Smelter 0.02 4.3 (1.3, 14.6)

Planing machine operator 0.17 5.4 (0.5, 58.8)

Spray painter 0.06 3.5 (0.9, 13.1)

Gas-cutting worker 0.68 1.7 (0.1, 18.9)

Total exposure time (yr) 0.32 0.5 (0.1, 1.9)

BP 0.98 1.0 (0.4, 3.0)

ECG 0.92 1.0 (0.7, 1.6)

Total exposure time (yr)*Type Of Work 0.46

Total exposure time (yr)*Welder 0.05 3.8 (1.0, 14.5)

Total exposure time (yr)*Assembler 0.08 3.4 (0.9, 13.1)

Total exposure time (yr)*Production

security and quality inspector

0.16 2.9 (0.7, 13.3)

Total exposure time(yr)*Smelter 0.23 2.3 (0.6, 9.3)

Total exposure time (yr)*Planing

machine operator

0.27 2.3 (0.5, 10.7)

Total exposure time(yr)*Spray painter 0.21 2.5 (0.6, 10.6)

Total exposure time (yr)*Gas-cutting

worker

0.23 3.4 (0.5, 24.1)

BP*Type Of Work 0.66

BP*Welder 0.62 1.5 (0.3, 6.7)

BP*Assembler 0.09 3.4 (0.8, 13.5)

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BP*Production security and quality

inspector

0.94 0.9 (0.2, 4.8)

BP*Smelter 0.49 1.9 (0.4, 10.9)

BP*Planing machine operator 0.72 0.6 (0.0, 13.3)

BP*Spray painter 0.26 3.1 (0.4, 23.4)

BP*Gas-cutting worker 0.97 0.0 (0.0, 1.2)

Step 6.The final model

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

538.9 71.0 9 0.00 72.7 9 0.00 72.7 9 0.00

a. Beginning Block Number 1. Method = Enter

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114

Variables in the Equation

Covariate P OR 95.0% CI

Type Of Work 0.00*

Welder 0.00* 3.7 (1.9, 7.2)

Assembler 0.03* 2.2 (1.1, 4.3)

Production security and quality

inspector

0.00* 2.7 (1.4, 5.0)

Smelter 0.00* 4.0 (1.8, 9.2)

Planing machine operator 0.06 3.9 (0.9, 16.6)

Spray painter 0.00* 4.4 (1.7, 11.4)

Gas-cutting worker 0.15 2.6 (0.7, 9.1)

Total exposure time (yr) 0.00* 1.5 (1.2, 1.8)

BP 0.04* 1.6 (1.0, 2.5)

The multivariable modelling process (a sensitivity test)

Step 1. Bivariate analysis (P<0.25*)

1. Department

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step

Change From Previous

Block

Χ2 df P Χ2

df P Χ2 df P

572.0 37.0 3 0.00 39.6 3 0.00 39.6 3 0.00

a. Beginning Block Number 1. Method = Enter

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115

Variables in the Equation

Covariate P. OR 95.0% CI

Department 0.00

Shipbuilding 0.00 3.5 (2.2, 5.8)

Ship-repair 0.00 5.0 (2.8, 9.0)

Production security 0.00 2.8 (1.6, 5.0 )

2. Total exposure time

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

567.0 46.0 1 0.00* 44.6 1 0.00 44.6 1 0.00

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

Covariate P OR 95.0% CI

Total exposure time (yr) 0.00* 1.7 (1.5, 2.1)

3. Electrocardiogram

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

611.4 0.18 1 0.68 0.2 1 0.68 0.2 1 0.68

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

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116

Covariate P OR 95.0% CI

ECG 0.68 1.1 (0.7, 1.6)

4. Blood pressure

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

608.6 3.1 1 0.08 3.0 1 0.08 3.0 1 0.08

a. Beginning Block Number 1. Method = Enter

Variables in the Equation

Covariate P OR 95.0% CI

BP 0.08* 1.5 (0.9, 2.2 )

Step 2.An initial multivariable model(P<0.05*)

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step

Change From Previous

Block

Χ2 df P Χ2

df P Χ2 df P

555.9 55.1 5 0.00 55.7 5 0.00 55.7 5 0.00

a. Beginning Block Number 1. Method = Enter

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117

Variables in the Equation

Covariate P OR 95.0% CI

Department 0.08

Shipbuilding 0.04 1.9 (1.0, 3.6)

Ship-repair 0.01 2.5 (1.2, 5.2)

Production security 0.03 2.0 (1.1, 3.7)

Total exposure time (yr) 0.00* 1.5 (1.2, 1.8)

BP 0.03* 1.6 (1.0, 2.5)

According to our research aim, department is one of the important risk factor so it was

decided not to exclude it from the model.

Step 3. Reintroduce variables excluded from the initial multivariable model

There was no variable excluded from step 2

Step 4. Reintroduce variables excluded from the bivariate analysis

ECG (not a confounder)

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

555.9 55.1 6 0.00 55.7 6 0.00 55.7 6 0.00

a. Beginning Block Number 1. Method = Enter

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118

Variables in the Equation

Covariate P OR 95.0% CI

Department 0.08

Shipbuilding 0.04 1.9 (1.0, 3.6)

Ship-repair 0.01 2.5 (1.2, 5.2)

Production security 0.03 2.0 (1.1, 3.7)

Total exposure time (yr) 0.00* 1.5 (1.2, 1.8)

BP 0.03* 1.6 (1.0, 2.5)

ECG 0.94 1.0 (0.7, 1.5)

Step 5. Interaction checking

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

546.1 67.0 12 0.00 65.5 12 0.00 65.5 12 0.00

a. Beginning Block Number 1. Method = Enter

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119

Variables in the Equation

Covariate P OR 95.0% CI

Department 0.01

Shipbuilding 0.21 1.6 (0.8, 3.4)

Ship-repair 0.00 4.2 (1.8, 10.2)

Production security 0.07 2.3 (0.9, 5.5)

Total exposure time (yr) 0.83 .8 (0.2, 4.4)

BP 0.17 1.9 (0.8, 4.6 )

Department*Total exposure time (yr) 0.45

Shipbuilding*Total exposure time (yr) 0.46 1.9 (0.4, 10.1)

Ship-repair*Total exposure time (yr) 0.68 1.4 (0.3, 7.7 )

Production security*Total exposure time

(yr)

0.62 1.6 (0.3, 9.6)

BP*Department 0.24

BP*Shipbuilding 0.78 .8 (0.2, 3.2)

BP*Ship-repair 0.14 .3 (0.1, 1.5)

BP*Production security 0.25 .4 (0.1, 1.9)

BP*Total exposure time (yr) 0.30 1.2 (0.8, 1.9)

Step 6.The final model

Omnibus Tests of Model Coefficientsa

-2 Log

Likelihood

Overall (score) Change From Previous Step Change From Previous Block

Χ2 df P Χ2

df P Χ2 df P

555.9 55.1 5 0.00 55.7 5 0.00 55.7 5 0.00

a. Beginning Block Number 1. Method = Enter

Page 136: AMBIENT HEAT EXPOSURE AND UROLITHIASIS AMONG

120

Variables in the Equation

Covariate P OR 95.0% CI

Department 0.08

Shipbuilding 0.04 1.9 (1.0, 3.6)

Ship-repair 0.01 2.5 (1.2, 5.2 )

Production security 0.03 2.0 (1.1, 3.7)

Total exposure time (yr) 0.00* 1.5 (1.2, 1.8 )

BP 0.03* 1.6 (1.0, 2.5)

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121

APPENDIX 2: Ethics Application Exempt

Dear Ms Haiming Luo

Project Title: The impacts of high ambient temperature on the prevalence of

urolithiasis among outdoor workers in Guangzhou, China

Ethics Category: Human

Status: Exempt

Exempt Number: 1000001329

This email is to advise that your application has been reviewed by the Chair, University

Human Research Ethics Committee (UHREC) and deemed exempt from the need for

UHREC review, approval and monitoring in conformity with sections 5.1.22 and 5.1.23 of

the National Statement on Ethical Conduct in Human Research (2007).

Please note that since this exemption has been granted, responsibility for ensuring that the

project is conducted in accord with the National Statement, with relevant legislation and with

QUT policies still rests with you, the investigator, and responsibility for monitoring

compliance rests with your Supervisor and/or Head of School. Please inform your Supervisor

and/or Head of School of any changes to the study protocol, also informing.

UHREC, via the Research Ethics Unit, if the study protocol changes in ways that might affect

this exemption, for example altering risks or the usage of personal information.

Please also note you are required to keep an auditable record of any human research that is

exempted from ethical review as per section 5.2.9 of the National Statement.

Please note that exemption is not equivalent to approval and therefore care must be taken to

accurately describe the conditions under which this study has been reviewed. UHREC

recommends the following statement be used when drafting manuscripts for publication:

"The QUT University Human Research Ethics Committee assessed this research as meeting

the conditions for exemption from HREC review and approval in accordance with section

5.1.22 of the National Statement on Ethical Conduct in Human Research (2007)."

Should you have any further queries please do not hesitate to contact the Research Ethics

Unit on 3138 5123.

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122

Regards,

Janette Lamb on behalf of the Chair UHREC

Research Ethics Unit | Office of Research

Level 4 | 88 Musk Avenue | Kelvin Grove

p: +61 7 3138 5123

e: [email protected]

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APPENDIX 3: GIHI Approval Letter

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APPENDIX 4: Information Collection Form to OHSOs

1. When was the period of highest temperature at the workplace in summer from 2003 to

2010 according the company‟s historical records? What were the highest temperature

records of different sites?

2. Could you estimate the outdoor working time (hours/day) and relevant workloads (light,

medium and heavy) for the following types of work? Welder, assembler, production

security and quality inspector, smelter, planing machine operator, spray painter and gas

cutting worker.

3. Did the company supply free drinking water to workers in shipbuilding and ship-repair

departments, and arrange regular water breaks for them especially in summer?

4. Did the company provide free meals for workers and employees in the company? If yes,

how many times?

5. Had the company ever noticed about the prevalence of urolithiasis according to the health

check files of 2003 to 2010? If yes, had any treatment ever been provided? What kinds of

treatment and at what time?

Participant Signature: Time:

Investigator Signature: Time: