Current Situation and Causes Analysis of Cadmium Pollution in the Kakehashi River Basin.

Cadmium (Cd) pollution is a public environmental problem worthy of attention. Long-term exposure to Cd may have adverse effects on human health. Our previous study showed that urinary concentration of Cd (U-Cd) in the residents decreased when Cd-polluted paddy soil was removed. However, from 2008 to 2014, the concentration of U-Cd increased. At the same time, the concentration of urinary ß2-microglobulin (ß2-MG), which is considered to be an early sign of cadmium-induced renal dysfunction, increased continuously. To find the cause of elevated urinary cadmium (U-Cd) in residents of cadmium-contaminated areas, we measured the concentration of cadmium in the blood (B-Cd) of 29 elderly residents (15 female and 14 male) and edible rice (R-Cd), and correlations between R-Cd, B-Cd, and U-Cd were analyzed in the formerly cadmium-polluted areas (the Kakehashi River basin). In 2016, we collected blood, urine, and rice samples from each participant. The analysis showed a significant correlation between age and B-Cd, U-Cd, and ß2-MG. However, there was no significant correlation between R-Cd and U-Cd, B-Cd, or ß2-MG concentrations. Although we found a slightly higher level of Cd in rice and urine than reported in 2008, we cannot be sure that it indicates an increased Cd contamination in the Kakehashi River basin because larger studies are required for such a conclusion. The increased urinary Cd concentrations in this area may be because Cd in tissues and organs returns to blood and urine as participants age, which leads to an increasing trend.

Cadmium body burden and health effects after restoration of cadmium-polluted soils in cadmium-polluted areas in the Jinzu River basin.

BACKGROUND: Itai-itai disease is caused by environmental cadmium (Cd) pollution in the Jinzu River basin in Japan. To reduce the Cd contamination of rice, soil restoration of paddy fields was carried out. We evaluated the effect of soil restoration on the health status of residents of the former Cd-polluted area. METHODS: Participants were 1,030 men and 944 women who lived in the area of restoration of Cd-polluted rice paddies. First morning urine was collected and urinary Cd, ß2-microglobulin (ß2MG), and N-acetyl-ß-D-glucosaminidase (NAG) levels were measured. Associations among age, years of residence before and after soil restoration, and urinary Cd, ß2MG, and NAG levels were evaluated by multiple regression analysis. RESULTS: The geometric mean (interquartile range) of urinary Cd (µg/g Cr) was 1.00 (0.58-1.68) in men and 1.67 (1.02-2.91) in women. The geometric means of urinary ß2MG (µg/g Cr) and NAG (U/g Cr) were 174.6 (92.6-234.2) and 1.47 (0.72-3.14) in men, and 217.6 (115.3-28.7) and 1.48 (0.73-2.96) in women, respectively. Urinary Cd, ß2MG, and NAG were significantly positively correlated (p < 0.01 all). Age and duration of residence in the Cd-polluted area before soil restoration were independently associated with urinary Cd, ß2MG, and NAG. Among the 916 participants who had resided in the area before the soil restoration, urinary Cd concentrations were significantly higher, thus by 1.03-fold (95% CI, 1.01-1.04) in men and 1.03-fold (95% CI, 1.01-1.05) in women, when the years of residence before soil restoration by each 5-years increment. By contrast, urinary Cd concentrations were significantly lower, thus 0.97-fold (95% CI, 0.96-0.99) lower in men and 0.97-fold (95% CI, 0.95-0.99) lower in women, by each 5-year increment of residence after soil restoration. A similar association was observed for urinary ß2MG concentration, and no significant association was observed for urinary NAG levels in men or women. CONCLUSIONS: Cd exposure and associated renal tubular dysfunction in residents of a former Cd-polluted area were influenced by Cd exposure from the environment prior to soil restoration. Soil restoration in Cd-polluted areas reduced the Cd exposure of local residents.

Effect of renal tubular damage on non-cancer mortality in the general Japanese population living in cadmium non-polluted areas.

This study aimed to clarify the cause-effect relationship between renal tubular damage and non-cancer mortality in the general Japanese population. We conducted a 19-year cohort study including 1110 men and 1,03 women who lived in three cadmium-non-polluted areas in 1993 or 1994. Mortality risk ratios based on urinary ß2-microglobulin (ß2MG) and N-acetyl-ß-glucosaminidase (NAG) concentrations were estimated for specific non-cancer diseases using the Fine and Gray competing risks regression model. In men, continuous urinary NAG (+1 µg/g cre) concentrations were significantly correlated with increased mortality caused by diseases of the respiratory system (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15). Urinary ß2MG (+100 µg/g cre) concentrations were significantly correlated with increased mortalities caused by kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.03), renal diseases (HR: 1.01, 95% CI: 1.00-1.03), renal failure (HR: 1.02, 95% CI: 1.00-1.03), and external causes of mortality (HR: 1.01, 95% CI: 1.00-1.02). In women, urinary NAG (+1 µg/g cre) concentrations were significantly associated with increased mortality caused by ischemic heart diseases (HR: 1.02, 95% CI: 1.00-1.04) and kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.04). Urinary ß2MG (+100 µg/g cre) concentrations were significantly correlated with increased mortality caused by cardiovascular diseases (HR: 1.01, 95%CI: 1.00-1.02), ischemic heart diseases (HR: 1.01, 95%CI: 1.00-1.02), and kidney and urinary tract diseases (HR: 1.02, 95% CI: 1.01-1.03). The present study indicates that renal tubular damage was significantly related to several non-cancer disease causes of mortality in Japan's general population living in cadmium-non-polluted areas.

A 30-year follow-up study in a former cadmium-polluted area of Japan: the relationship between cadmium exposure and ß2-microglobulin in the urine of Japanese people.

Cadmium (Cd) is an environmental pollutant. Long-term exposure to Cd may lead to adverse health effects in humans. Our epidemiological studies showed that urinary Cd (U-Cd) concentrations increased from 2008 through 2014, although they decreased from 1986 through 2008. The aim of this study was to elucidate the long-term effects of the changing trend of cadmium exposure levels (U-Cd) on residents' renal function within 30 years after Cd exposure ceased. In 2016, urine samples were collected from each subject by visiting 20 elderly Japanese people (9 females and 11 males) living in the Kakehashi River basin, a previously Cd-polluted area in Ishikawa, Japan. The geometric means of the ß2-microglobulin (ß2-MG) and urinary Cd (U-Cd) continued to increase from 2014 until 2016. Furthermore, Cd concentration and ß2-MG in urine were still higher than those in the non-polluted areas in Japan. Multivariate linear regression was performed to associate ß2-MG (dependent variable) and U-Cd with sex and age (independent variables). Significant correlations were found among age, U-Cd, and ß2-MG, and these were clearer in females than in males. In summary, we propose that three decades after Cd exposure ceased, age is associated with ß2-MG more strongly than Cd for bodily impact. Moreover, renal tubular dysfunction is irreversible and worsens after exposure to Cd, with females being more sensitive to exposure.

Possible Association between Physical and Cognitive Function and Stumbling and Falling in Elderly Workers.

The aim of this paper is to examine the association between physical and cognitive function and stumbling and falling in elderly workers by conducting work-related questionnaire surveys and physical and cognitive function measurements. A total of 611 men and 121 women aged 40-69 years who participated in physical function measurements between June 2017 and June 2021 were included in the study. The general physical function measurements of upper and lower limb muscle strength, dynamic and static balance, and agility and cognitive function included grip strength, Repeated Rise Test, Trail Making test (TMT), and Three-Meter Time Up Go Test (TUG). We also asked the men and women about their experience of falling and stumbling. Logistic regression analysis showed significant odds ratios (OR) for the associations between stumbling in men and age (OR: 1.98), mental burden (OR: 2.44), frequency of field work (OR: 1.74), seated stepping test count (OR: 0.95), and TMTB time (OR: 0.99). Significant ORs were found between falling in men and age (OR: 2.55), mental burden (OR: 2.40), exercise habits (OR: 2.55), and smoking (OR: 2.00). Significant ORs were found between stumbling in women and d_TUG (OR: 1.59) and mental burden (OR: 6.42). The study suggests that there may be an association between cognitive and physical decline and stumbling and falling in elderly workers.

Renal tubular dysfunction and cancer mortality in the Japanese general population living in cadmium-non-contaminated areas.

The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary ß2-microglobulin (ß2MG) and N-acetyl-ß-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02-1.19, pancreas: HR, 1.10, 95%CI, 1.02-1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67-0.96) and for ß2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93-1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.

Effects of Alcohol Consumption and Smoking on the Onset of Hypertension in a Long-Term Longitudinal Study in a Male Workers' Cohort.

AIM: To determine the effects of alcohol consumption and smoking on the onset of hypertension in a long-term longitudinal study. METHODS: 7511 non-hypertensive male workers were enrolled. This cohort study was performed over an 8-year period using the results of the annual workers-health screening. The end-point was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or use of antihypertensive drugs. For alcohol consumption, weekly alcohol intake (g ethanol/week) was estimated (1 "gou" = 22 g ethanol). Annual survey data were analyzed by pooled logistic regression that included alcohol consumption, smoking, age, body mass index, job schedule types, habitual exercise, and blood test measurements into the statistical model. RESULTS: A significant positive dose-response relationship between alcohol consumption and onset of hypertension was observed, with synergistic health effects present. Compared with abstainers and nonsmokers, the adjusted odds ratios (95% confidence interval) for the onset of hypertension were: 1.51 (1.27-1.79) for 154 g ethanol/week and nonsmokers, and 1.81 (1.54-2.11) for 154 g ethanol/week and smokers. An interaction between alcohol and smoking was confirmed. CONCLUSIONS: This study provided information useful to the prevention of hypertension. By reducing alcohol consumption and smoking simultaneously, the risk of hypertension may be considerably lowered.

The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan.

We evaluated the association between urinary cadmium concentration (uCd, µg/g Cr) and risk of cause-specific mortality according to urinary ß2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and ß2-MG were evaluated in a survey in 1981-1982, where those participants were followed-up over 35 years later. Among the participants with a urinary ß2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with <5.0 for cardiovascular disease [HR 1.92 (1.08-3.40) for men, 1.71 (1.07-2.71) for women], pneumonia or influenza [2.10 (1.10-4.00) for men, 2.22 (1.17-4.19) for women], and digestive diseases [for men; 3.81 (1.49-9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary ß2-MG of ≥1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

Estimation of Benchmark Dose of Cumulative Cadmium Exposure for Renal Tubular Effect.

OBJECTIVES: The aim of this study was to determine the no observed adverse effect level (NOAEL), the lowest observed adverse effect level (LOAEL) and the benchmark dose low (BMDL) of cadmium exposure by re-evaluation of the dose-response relationship between cumulative cadmium exposure and renal tubular damage reported previously. METHODS: The participants were workers (326 men and 114 women) employed for at least three months between 1931 and 1982. Blood cadmium (Cd-B) and air cadmium (Cd-A) were collected at regular intervals with urinary ß2-microglobulin as the tubular effect marker. Cumulative Cd-A and Cd-B were estimated by multiplying concentration and working period. The BMDL was calculated using Benchmark Dose Software (version 3.1.2). The benchmark response (BMR) was set at 5% or 10%. RESULTS: By logistic regression, the NOAEL of mean cumulative Cd-B was 7122 months nmol/L. The LOAEL of cumulative Cd-A and least-squares cumulative Cd-B was 691 yrs µg/m3 and 8586 months nmol/L, respectively. Among various models for dose-response relationships, a probit model was adopted as the best fitting model. The obtained BMDLs of cumulative Cd-A were 272.3 yrs µg/m3 (BMR5%) and 707.5 yrs µg/m3 (BMR10%). The BMDLs of mean cumulative Cd-B were 3967.2 months nmol/L (BMR5%) and 7798.1 months nmol/L (BMR10%). The BMDLs of least-squares cumulative Cd-B were 3588.6 months nmol/L (BMR5%) and 8616.3 months nmol/L (BMR10%). Assuming a working period of 40 years, the BMDLs for BMR10% corresponded to 17.7 µg/m3 (Cd-A) and 1.8~2.0 µg/L (Cd-B). DISCUSSION: This study provides new valuable information to enhance the reliability of limit values and thereby make a significant contribution to preventing the health effects of Cd in exposed workers.

The relationship between cadmium exposure and renal volume in inhabitants of a cadmium-polluted area of Japan.

This follow-up study was conducted over 30 years in a cadmium-polluted area of Japan. Urinary cadmium (U-Cd) concentration decreased by nearly half from 1986 to 2008 in men and women. However, it increased from 2008 to 2014 and maintained similar levels in 2016. Because renal atrophy may induce an increase in U-Cd, kidney volumes were determined using magnetic resonance imaging (MRI) scans in 2018. Based on the MRI results, we divided the participants into two groups, namely the normal group (n = 6, three men and three women) and the lesion group (n = 6, three men and three women). The level of urinary N-acetyl-ß-d-glucosaminidase/creatinine (U-NAG/Cr) in the lesion group was significantly higher than in the normal group. The level of serum alkaline phosphatase (Al-P) was positively associated with U-Cd. Age and renal cortex volumes showed significantly negative associations. However, U-Cd and renal cortex and kidney volumes showed no significant associations. These results suggest that U-NAG and serum Al-P were sensitive biomarkers to reflect renal tubular dysfunction and bone damage caused by cadmium poisoning. Individuals chronically exposed to Cd should be observed carefully, due to the increased effect of aging on renal cortex volumes.

Environmental cadmium exposure and noncancer mortality in a general Japanese population in cadmium nonpolluted regions.

The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U-Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U-Cd (µg/g cre) adjusted for urinary creatinine. Hazard ratio (HR) and 95% confidence interval (95% CI) for continuous U-Cd or the quartiles of U-Cd were calculated for noncancer mortality. By applying a Fine and Gray competing risk model, continuous U-Cd (+1 µg/g cre) showed significant HR for cardiocerebrovascular diseases (HR 1.05, 95% CI: 1.00-1.11), cerebrovascular diseases (HR 1.08, 95% CI: 1.01-1.16), and cerebral infarction (HR 1.11, 95% CI: 1.04-1.20) in men. However, notable significant HR for continuous and quartered U-Cd were not observed in women. In this study, U-Cd was associated with increased cardiocerebrovascular mortality in a general Japanese population, suggesting that environmental cadmium exposure is detrimental to the life prognosis in cadmium nonpolluted regions in Japan.

Relationship between urinary ß2 -microglobulin concentration and mortality in a cadmium-polluted area in Japan: A 35-year follow-up study.

The relationship between urinary ß2 -microglobulin (ß2 -MG) and the risk of all-cause mortality and cause-specific mortality in a cadmium (Cd)-polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35-year follow-up. The subjects had been participants in the 1981-1982 health impact survey that assessed Cd-induced renal dysfunction, as measured by the urinary ß2 -MG concentration. Hazard ratios were calculated to assess the risk of all-cause and cause-specific mortality according to the urinary ß2 -MG concentrations. Risk ratios (RRs) were assessed using the Fine and Gray regression model to account for competing risks of cause-specific mortality. The mortality rate was significantly higher in participants with urinary ß2 -MG concentrations >1000 µg/g creatinine (Cr) for men and >300 µg/g Cr for women. In the proportional hazard model, higher urinary ß2 -MG concentrations were associated with higher risks of circulatory disease, digestive system diseases, and kidney and urinary tract diseases in men and women, and with senility for women. However, when competing risk was accounted for, the RRs were significantly higher only for kidney and urinary tract diseases in men and women (RR for each increment of 1000 µg/g Cr [95% confidence interval]: 1.02 [1.00-1.04] for men, and 1.01 [1.00-1.02] for women). The long-term prognosis of participants with renal tubular dysfunction was poor, most likely due to kidney and renal tract diseases.

Lifetime Cadmium Exposure and Mortality for Renal Diseases in Residents of the Cadmium-Polluted Kakehashi River Basin in Japan.

Very few studies have investigated the dose-response relationship between external cadmium (Cd) exposure and mortality. We aim to investigate the relationship between lifetime Cd intake (LCd) and mortality in the Cd-polluted Kakehashi River basin in Japan. Mortality risk ratios for a unit of increase of LCd and urinary Cd were analyzed using Cox's proportional model. LCd was estimated based on residency and Cd in rice produced in their living areas. In men, mortality for all causes was significantly increased for a 10-µg/g Cr increase in urinary Cd, but not for a 1-g increase in LCd. In women, mortality risks for all causes and renal diseases, particularly renal failure, were significantly increased for a 10-µg/g Cr increase in urinary Cd. Similarly, mortality risks for renal diseases and renal failure were significantly increased for a 1-g increase of LCd in women. Comparing the contribution of two exposure markers to increased mortality in women, LCd was more effective for increasing mortality risks for renal diseases and renal failure, while urinary Cd contributed more to increased mortality risk for all causes. LCd may show a better dose-response relationship with mortality risk for renal diseases in women.

Relationship between cancer mortality and environmental cadmium exposure in the general Japanese population in cadmium non-polluted areas.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd (U-Cd) on cancer mortality in the general Japanese population. A 19-year cohort study was conducted in 1107 men and 1697 women who lived in three Cd non-polluted areas in Japan. Mortality risk ratio and 95% confidence interval (95%CI) for continuous U-Cd were estimated for all malignant neoplasms and specific cancers using a Fine and Gray competing risks regression model. The all-cause, including cancer and non-cancer mortality rates per 1000 person-years were 29.8 and 13.9 in men and women, respectively. By using Fine and Gray's method, continuous U-Cd adjusted for creatinine (+1 µg/g cre) was significantly related to mortalities for all malignant neoplasms (risk ratio = 1.06, 95%CI: 1.02-1.11) and pancreas (risk ratio = 1.13, 95%CI: 1.03-1.24) in women. In the present study, U-Cd was significantly associated with increased cancer mortality in the general Japanese population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan.

Health status of workers approximately 60 years of age and the risk of early death after compulsory retirement: A cohort study.

OBJECTIVES: The increasing number of working elderly people has enhanced the importance of workplace health promotion activities. We investigated the association between the health status of workers approximately 60 years of age and the risk of all-cause mortality after compulsory retirement in Japan. METHODS: The 2026 participants (1299 males and 727 females) had retired from a metal-products factory at ≥60 years of age. Baseline health examinations were conducted at 60 years of age and included questions about medical history and lifestyle factors; the participants also underwent a physical examination. The participants were followed up annually by mail for an average of 7.4 years. The association between health status at age 60 years and the risk of all-cause mortality was assessed by Cox proportional hazards regression analysis. RESULTS: During the study, 71 deaths were reported. The age- and sex-adjusted hazard ratio (HR [95% confidence interval]) for all-cause mortality was higher for males (HR, 3.41 [1.73-6.69]) compared with females, participants with a low body mass index (<18.5 kg/m2 ; HR 3.84 [1.91-7.73]) compared with normal body weight, smokers (HR, 2.63 [1.51-4.58]) compared with nonsmokers, and those with three or more of four metabolic abnormalities (obesity, high blood pressure, dyslipidemia, and glucose intolerance) (HR 2.29 [1.04-5.02]) compared with no metabolic abnormalities. The associations were unaffected by adjustment for these factors. CONCLUSION: Maintenance of an appropriate body weight, smoking cessation, and elimination of metabolic syndrome are required for older workers to prevent early death after retirement.

Cancer Mortality in Residents of the Cadmium-Polluted Jinzu River Basin in Toyama, Japan.

After 26 years, we followed up 7348 participants in a 1979-1984 health screening survey in the Jinzu River basin, the heaviest cadmium-polluted area in Japan. We assessed the associations of cadmium exposure levels and mortality from cancer and renal damage, indicated by records of proteinuria and glucosuria in the original survey. Mortality risks (hazard ratios) were analyzed using the Cox proportional hazards model, stratified by sex, after adjusting for age, smoking status, and hypertension, as indicated in the original survey records. In men, the adjusted hazard ratio for mortality from lung cancer was significantly lower in individuals residing in an area of historically high cadmium exposure and in subjects with a historical record of proteinuria, glucosuria, and glucoproteinuria. The risk of mortality from prostate cancer was borderline higher in cadmium-exposed men. In women, historical cadmium exposure was not associated with an increased risk of mortality from malignant neoplasms, but the adjusted hazard ratios for death from total malignant neoplasms or from renal and uterine cancers were significantly higher in exposed subjects with a historical record of proteinuria, glucosuria, and glucoproteinuria. These findings suggest that women residing in cadmium-polluted areas who exhibit markers of renal damage may be at risk of dying of cancer.

[Work accommodation at the time of Return-to-Work for workers on sick leave: a qualitative systematic review with recommendations for Return-to-work Guidance 2017].

OBJECTIVE: We conducted a systematic review to determine whether work accommodation at the time of return-to-work (RTW) following a period of sick leave would improve work-related outcomes. Using a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, we developed recommendations applicable to the field of occupational health in Japan. METHOD: We approached our review question for "Evidence-based Return-to-work Guidance in Occupational Health 2017 (RTW 2017) " using a PICO framework (P: workers on sick leave; I: work accommodation; C: usual care; O: improvement of work-related outcomes, such as shortened sick leave period or lower rate of sick leave recurrence). To identify relevant intervention studies about work accommodation at the time of RTW, for example, modified work or partial RTW, we searched Cochrane Library, PubMed, and ICHUSHI Web using keywords/phrases such as workplace accommodation, partial RTW, rehabilitation, and modified work. Although we found no systematic reviews, we did identify 632 randomized controlled trials and cohort studies. Two researchers screened them independently using selection and exclusion criteria defined by the RTW guidance committee in the scope. For intervention studies, we extracted PICO and evaluated risk of bias using RevMan 5.3. For cohort studies, we applied the Newcastle-Ottawa scale for evaluation of risk of bias. We then evaluated the body of evidence based on risk of bias, indirectness, inconsistency, imprecision, and publication bias using GRADEPro GDT. Finally, we adopted Evidence to Decision from GRADE and developed recommendations based on anonymous panels' votes. RESULT: We identified three relevant studies, which were one randomized controlled trial and two cohort studies, on Partial RTW or modified work for musculoskeletal disorders. Although we could not conduct a meta-analysis, our qualitative systematic review of these studies led us to conclude that partial RTW could shorten the period of sick leave and modified work could lower the recurrence rates of sick leave. Therefore, "Work accommodation at the time of RTW could be provided for workers on sick leave for musculoskeletal disorders" was weakly recommended on the basis of low evidence. CONCLUSIONS: Our recommendation, though plausible, is weak, as it is based on evidence from a small number of studies of foreign occupational health systems. Development of robust recommendations will require accumulation of additional information on diverse factors, such as cost-effectiveness, and on other diseases, for example, mental health disorders or malignant diseases, in Japan.

Increase of lifetime cadmium intake dose-dependently increased all cause of mortality in female inhabitants of the cadmium-polluted Jinzu River basin, Toyama, Japan.

BACKGROUND: Exposure to cadmium (Cd) via food is supposed to affect life prognosis of inhabitants of Cd-polluted area in Japan. However, there have been few reports demonstrating a significant relationship between the amount of Cd intake and mortality. We aimed to investigate the relationship between mortality and individual lifetime Cd intake (LCd) in inhabitants of the polluted Jinzu River basin, Toyama, Japan. METHODS: We conducted a 26-year follow-up survey in 2407 inhabitants (1208 men and 1199 women) who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The calculation of LCd in each inhabitant was based on the formula of Nogawa (Nogawa et al., 1989): (mean Cd concentration in rice of the present hamlet × 333.5 g/day + 34 µg/day) × 365 days/year × number of years of residence in the present hamlet + 50 µg/day × 365 days/year × number of years living in Cd non-polluted regions. In this formula, 333.5 g/day is the 1970 average daily intake of rice in this area, 34 µg/day is the Cd intake from foods other than rice in this area, and 50 µg/day is the average intake of Cd in non-polluted areas in Japan. Mortality risk ratios of LCd for all and specific causes were estimated after adjustments for age at baseline, smoking status, and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. RESULTS: The mortality risk ratios of LCd (+ 1 g) for all causes in women were significantly dose-dependently increased (risk ratio: 1.08). Relative risk of LCd for kidney and urinal tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly higher in women. CONCLUSIONS: The present study documents that individual LCd dose-dependently decreased life prognosis over long-term observation in women. LCd was significantly related to the increased mortality for renal disease and toxic effect of Cd in women. The result provides clear evidence that life prognosis was adversely affected by Cd-exposure, especially in women.

Relationship between mortality and rice cadmium concentration in inhabitants of the polluted Jinzu River basin, Toyama, Japan: A 26 year follow-up.

The aim of this study was to investigate the relationship between mortality and rice cadmium (Cd) concentration in inhabitants of a polluted area in Japan. The target subjects were inhabitants of the Jinzu River basin who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The mean rice Cd concentration in each hamlet was used as an index of the Cd exposure. We conducted a 26 year follow-up survey in 3281 inhabitants (1544 men and 1737 women) whose data regarding the rice Cd concentration were available. Mortality risk ratios for all and specific causes were estimated after adjustments for age at baseline, smoking status and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. The mortality risk ratios of rice Cd concentration (+0.1 ppm) for all causes in women were significantly increased (risk ratio: 1.04). Furthermore, the relative risks of rice Cd concentration for kidney and urinary tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly increased in both sexes. These findings indicated that increased rice Cd concentration decreased the prognosis for life over a long-term observation in women. This result provides important information for determining the worldwide standard for allowable rice Cd concentration.

Causes of death in patients with Itai-itai disease suffering from severe chronic cadmium poisoning: a nested case-control analysis of a follow-up study in Japan.

OBJECTIVE: To clarify the causes of deaths among patients with Itai-itai disease and severe cadmium (Cd) poisoning. DESIGN: Nested case-control analysis of a population-based cohort study. SETTING: Database of patients with Itai-itai disease and residents of Cd-polluted areas, maintained by the Ministry of Environment, Japan. PARTICIPANTS: Subjects included 142 women with Itai-itai disease, 111 women with Cd-induced renal tubular dysfunction and 253 controls matched for sex, age and occupation. All subjects participated in a health impact survey between 1979 and 1984 and were followed until 30 November 2005. MAIN OUTCOMES AND MEASURES: Adjusted HRs with 95% CIs for cause of death in women with Itai-itai disease and screened female cases with tubular dysfunction were compared with matched pair controls, using Cox's proportional hazard model. Vital statistics data were used to determine cause of death. Direct causes of death from autopsy records were used in 29 patients who died from Cd poisoning. RESULTS: The most common cause of death among patients with Itai-itai disease was pneumonia, with a significantly increased adjusted HR of 4.54 (95% CI 2.65 to 7.76). Renal diseases were the most common cause of death in renal tubular dysfunction cases, with an increased HR of 12.0 (95% CI 3.92 to 36.8). The adjusted HR for renal diseases was also significantly increased in patients with Itai-itai disease (19.49 (95% CI 6.43 to 59.09)), with a greater impact on mortality of patients with Itai-itai disease than screened cases. The HR for gastrointestinal (GI) diseases was significantly increased (13.79 (95% CI 3.87 to 49.10)) in patients, especially in the first 10 years (37.1 (4.81 to 286.0)). CONCLUSIONS: Among patients with Itai-itai disease, pneumonia and GI diseases contributed to increased mortality risk. Renal disease is also a significant mortality risk in patients with Itai-itai disease and women with renal tubular dysfunction.