Urinary and salivary endocrine measurements to complement Tanner staging in studies of pubertal development.

BACKGROUND: Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. OBJECTIVE: Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. METHODS: Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007-2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. RESULTS: Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. CONCLUSIONS: Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006).

BACKGROUND: During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users. METHODS: Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status. RESULTS: Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 µg/ml (n = 91, range <0.002-0.051 µg/ml) and 0.02 µg/ml (n = 32, range <0.004-0.069 µg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %). CONCLUSION: Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Timing of maturation and predictors of Tanner stage transitions in boys enrolled in a contemporary British cohort.

This study describes the timing of puberty in 8- to 14-year-old boys enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of advanced pubic hair stages. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported pubic hair Tanner staging collected annually. We used survival models to estimate median age of attainment of pubic hair stage >1, stage >2 and stage >3 of pubic hair development. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of pubic hair stages. Approximately 5% of the boys reported Tanner pubic hair stage >1 at age 8; 99% of boys were at stage >1 by age 14. The estimated median ages of entry into stages of pubic hair development were 11.4 years [95% confidence interval (CI) 11.3, 11.4] for stage >1, 12.7 years [95% CI 12.7, 12.8] for stage >2 and 13.5 years [95% CI 13.5, 13.6] for stage >3. Predictors of younger age at Tanner stage >1 included low birthweight, younger maternal age at delivery and being taller at age 8. Associations were found between younger age at attainment of stage >2 and gestational diabetes and taller or heavier body size at age 8. Being taller or heavier at age 8 also predicted younger age at Tanner stage >3. The results give added support to the strong influence of pre-adolescent body size on male pubertal development; the tallest and heaviest boys at 8 years achieved each stage earlier and the shortest boys later. Age at attainment of pubic hair Tanner stages in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. This cohort will continue to be followed for maturational information until age 17.

Nitrates in drinking water and methemoglobin levels in pregnancy: a longitudinal study.

BACKGROUND: Private water systems are more likely to have nitrate levels above the maximum contaminant level (MCL). Pregnant women are considered vulnerable to the effects of exposure to high levels of nitrates in drinking water due to their altered physiological states. The level of methemoglobin in the blood is the biomarker often used in research for assessing exposure to nitrates. The objective of this study was to assess methemoglobin levels and examine how various factors affected methemoglobin levels during pregnancy. We also examined whether differences in water use practices existed among pregnant women based on household drinking water source of private vs. public supply. METHODS: A longitudinal study of 357 pregnant women was conducted. Longitudinal regression models were used to examine changes and predictors of the change in methemoglobin levels over the period of gestation. RESULTS: Pregnant women showed a decrease in methemoglobin levels with increasing gestation although <1% had levels above the physiologic normal of 2% methemoglobin, regardless of the source of their drinking water. The multivariable analyses did not show a statistically significant association between methemoglobin levels and the estimated nitrate intake from tap water among pregnant women around 36 weeks gestation (ß = 0.046, p = 0.986). Four women had tap water nitrate levels above the MCL of 10 mg/L. At enrollment, a greater proportion of women who reported using water treatment devices were private wells users (66%) compared to public system users (46%) (p < 0.0001). Also, a greater proportion of private well users (27%) compared to public system users (13%) were using devices capable of removing nitrate from water (p < 0.0001). CONCLUSION: Pregnant women potentially exposed to nitrate levels primarily below the MCL for drinking water were unlikely to show methemoglobin levels above the physiologic normal. Water use practices such as the use of treatment devices to remove nitrates varied according to water source and should be considered in the assessment of exposure to nitrates in future studies.

A review of events that expose children to elemental mercury in the United States.

Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of elemental mercury exposures in children, describe the location and proportion of children affected, and make recommendations on how to prevent these exposures. In this review, we excluded mercury exposures from coal-burning facilities, dental amalgams, fish consumption, medical waste incinerators, or thimerosal-containing vaccines. We reviewed federal, state, and regional programs with data on mercury releases along with published reports of children exposed to elemental mercury in the United States. We selected all mercury-related events that were documented to expose (or potentially expose) children. Primary exposure locations were at home, at school, and at others such as industrial property not adequately remediated or medical facilities. Exposure to small spills from broken thermometers was the most common scenario; however, reports of such exposures are declining. The information reviewed suggests that most releases do not lead to demonstrable harm if the exposure period is short and the mercury is properly cleaned up. Primary prevention should include health education and policy initiatives.

A review of events that expose children to elemental mercury in the United States: [review] / Uma revisão dos eventos que expõem as crianças ao elemento mercúrio nos Estados Unidos: [revisão]

Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of elemental mercury exposures in children, describe the location and proportion of children affected, and make recommendations on how to prevent these exposures. In this review, we excluded mercury exposures from coal-burning facilities, dental amalgams, fish consumption, medical waste incinerators, or thimerosal-containing vaccines. We reviewed federal, state, and regional programs with data on mercury releases along with published reports of children exposed to elemental mercury in the United States. We selected all mercury-related events that were documented to expose (or potentially expose) children. Primary exposure locations were at home, at school, and at others such as industrial property not adequately remediated or medical facilities. Exposure to small spills from broken thermometers was the most common scenario; however, reports of such exposures are declining. The information reviewed suggests that most releases do not lead to demonstrable harm if the exposure period is short and the mercury is properly cleaned up. Primary prevention should include health education and policy initiatives.

Uma preocupação pela exposição de crianças ao elemento mercúrio estimulou a Agência para Substâncias Tóxicas e Registro de Doenças e os Centros para Controle e Prevenção de Doenças a rever as fontes de exposição a este elemento por crianças, descrever a locação e proporção de crianças afetadas e fazer recomendações de como prevenir essas exposições. Nesta análise, foi excluída a exposição a mercúrio em instalações de queima de carvão, amálgamas dentários, consumo de peixes, incineradores de lixo hospitalar ou vacinas contendo timerosal. Analisamos programas regionais, estaduais e federais com dados sobre liberação de mercúrio, juntamente com relatórios de crianças expostas ao elemento nos Estados Unidos. Selecionamos todos os eventos relacionados ao mercúrio que documentaram exposição (ou potencial exposição) de crianças. As principais localidades de exposição foram em casa, na escola e outras como indústrias não adequadas ou instalações médicas. A exposição a pequenos derramamentos de termômetros quebrados foram o cenário mais comum; todavia, relatos de tais exposições estão diminuindo. A informação analisada sugere que a maior parte dos comunicados não conduz a danos demonstráveis se o período de exposição for curto e o mercúrio for devidamente limpo. A prevenção primária deve incluir educação em saúde e iniciativas de políticas.

Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort.

This study describes the timing of puberty in 8- to 13-year-old girls enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of menarche. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported Tanner staging and menstrual status information collected annually from daughters up to age 13. We used survival models to estimate median age of attainment of stage >1 and stage >2 of breast and pubic hair development and of menarche. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of menarche. About 12% of girls reported Tanner breast stage >1 at age 8; 98% of girls were above stage 1 by age 13. For pubic hair, 5% and 95% of girls had attained a stage >1 by 8 and 13 years, respectively. The estimated median age of entry into stage >1 of breast development was 10.14 years (95% confidence interval [CI], 10.08, 10.19), and for pubic hair development the median age was 10.92 years [95% CI, 10.87, 10.97]. One girl (out of 2953) had attained menarche by age 8; 60% had attained menarche by age 13. The estimated median age at menarche was 12.93 years [95% CI, 12.89, 12.98]. Prenatal predictors of menarche by age 11 (12% of girls) included earlier maternal age at menarche, high maternal pre-pregnancy body mass index, smoking during the third trimester, and non-white race; the single postnatal predictor was the girl's body size at 8 years. Age at attainment of breast and pubic hair Tanner stage and age at menarche in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. The results also give added support to the strong influence of maternal maturation, pre-adolescent body size and race on the timing of a girl's menarche. This cohort will continue to be followed for maturational information until age 17.

A review of events that expose children to elemental mercury in the United States.

OBJECTIVE: Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of elemental mercury exposures in children, describe the location and proportion of children affected, and make recommendations on how to prevent these exposures. In this review, we excluded mercury exposures from coal-burning facilities, dental amalgams, fish consumption, medical waste incinerators, or thimerosal-containing vaccines. DATA SOURCES: We reviewed federal, state, and regional programs with information on mercury releases along with published reports of children exposed to elemental mercury in the United States. We selected all mercury-related events that were documented to expose (or potentially expose) children. We then explored event characteristics (i.e., the exposure source, location). DATA SYNTHESIS: Primary exposure locations were at home, at school, and at other locations such as industrial property not adequately remediated or medical facilities. Exposure to small spills from broken thermometers was the most common scenario; however, reports of such exposures are declining. DISCUSSION AND CONCLUSIONS: Childhood exposures to elemental mercury often result from inappropriate handling or cleanup of spilled mercury. The information reviewed suggests that most releases do not lead to demonstrable harm if the exposure period is short and the mercury is properly cleaned up. RECOMMENDATIONS: Primary prevention should include health education and policy initiatives. For larger spills, better coordination among existing surveillance systems would assist in understanding the risk factors and in developing effective prevention efforts.

In utero exposure to a brominated flame retardant and male growth and development.

Whether environmental exposures alter the timing of puberty is the subject of increasing interest as pubertal age may have consequences for long term health. This study examines the association between exposure to a brominated flame retardant, polybrominated biphenyl (PBB), and puberty and growth. The population consists of sons born to women accidentally exposed to PBBs during 1973-74. Sons 5 to 17 years reported Tanner Stages and answered questions regarding current growth in a mailed questionnaire. Sons 18 to 30 years of age participated in a telephone interview in which they reported retrospective measures of development. Among sons 5-17 years, those with highest exposure (>3 ppb) were less likely to report advanced Tanner stage genital development (OR=0.4, 95% CI: 0.2-0.9) and were less likely to report advanced pubic hair development (OR=0.5; 95% CI: 0.2-1.0), after adjusting for current age, compared to those with lowest exposure (<= 1 ppb). No differences were seen in growth among sons 5-17. However, among sons 18-30 years, those with higher exposure were more likely to weigh less and have lower BMI as adults (test of trend p=0.01 and 0.04, respectively). They were less likely to recall being tall (OR=0.5; 95% CI 0.2-0.9) or heavy (OR=0.6; 95% CI 0.3-1.1) compared to their peers at age 11 years. These results suggest that sons exposed to PBBs in utero may be more likely to have delayed puberty. Further research is needed to corroborate these findings among structurally related compounds and shed light on the biological mechanisms that may be disrupted during puberty and development.

Keyboard use and musculoskeletal outcomes among computer users.

BACKGROUND: In this review, the epidemiological evidence examining associations between upper extremity musculoskeletal symptoms and disorders and keyboard use intensity (hours of computer use-per day or per-week) and computer user posture was explored. METHODS: An OVID Medline literature search was conducted to identify papers published in the peer-reviewed medical literature between 1966 and November, 2005. A total of 558 citations were found and reviewed. Those papers in which associations between musculoskeletal outcomes and (1) posture (ascertained by a study investigator) or (2) computer use, in units of hours-per-day, hours-per-week, or as a percent of work-time, were included in the review. RESULTS: Thirty-nine epidemiological studies examining associations between computer use and MSD outcomes were identified. While the observational epidemiological literature was heterogeneous, some trends did emerge. It appears that the most consistent finding was the association observed between hours keying and hand/arm outcomes. Associations between some postural effects and musculoskeletal outcomes may also be inferred from the literature. In particular, placing the keyboard below the elbow, limiting head rotation, and resting the arms appears to result in reduced risk of neck/shoulder outcomes. Minimizing ulnar deviation and keyboard thickness appears to result in reduced risk of hand/arm outcomes. CONCLUSIONS: Several methodological limitations, including non-representative samples, imprecise or biased measures of exposure and health outcome, incomplete control of confounding, and reversal of cause and effect, may contribute to the heterogeneity of observed results. Suggestions are made for improving the validity of future investigations.

Job strain and risk of musculoskeletal symptoms among a prospective cohort of occupational computer users.

OBJECTIVES: Most previous studies of the association between psychosocial stress and musculoskeletal illness among computer users have been cross-sectional and have yielded inconsistent results. The association between a measure of psychosocial stress, "job strain", and incident neck-shoulder and arm-hand musculoskeletal symptoms was investigated among recently hired computer users. METHODS: The participants worked for one of several large employers and were followed prospectively for 6 months. The "job demands" and "decision latitude" subscales of the Job Content Questionnaire were used to estimate the job-strain quadrants and a ratio measure of job strain which was subsequently categorized. Incident musculoskeletal symptoms were obtained with weekly diaries. Proportional hazards models were used to estimate associations between job strain and incident musculoskeletal symptoms. RESULTS: Those in the high-strain quadrant were at increased risk of neck-shoulder symptoms [hazard ratio (HR) 1.65, 95% confidence interval (95% CI) 0.91-2.99] when compared with those in the low-strain quadrant. Those in the highest strain-ratio category were also at increased risk of neck-shoulder symptoms when compared with those in the lowest strain-ratio category (HR 1.52, 95% CI 0.88-2.62). Modification by previous years of computer use was observed, with an elevated risk observed for those in the highest job-strain ratio category who also had low previous computer use (HR 3.16, 95% CI 1.25-8.00). There did not appear to be an association between either measure of job strain and incident arm-hand symptoms. CONCLUSIONS: In this cohort, workers who reported high job strain were more likely to develop neck-shoulder symptoms.

Epidemiology of musculoskeletal disorders among computer users: lesson learned from the role of posture and keyboard use.

Reports in the scientific literature and lay press have suggested that computer users are at increased risk of upper extremity musculoskeletal disorders (MSDs). Early studies often found elevated rates of MSD outcomes among keyboard users when compared to non-users. Attention soon focused on specific aspects of keyboard work that might be responsible for the observed rate increase. In this review, the epidemiological evidence examining associations between MSD outcomes and computer user posture and keyboard use intensity (hours of computer use per day or per week) are examined. Results of epidemiological studies of posture and MSD outcomes have not been entirely consistent. Reasons for the inconsistency in results include cross-sectional study design (with possible failure to assure that measured exposure preceded health effect), imprecision of posture measures used, and difficulties involved in analyzing multiple related variables. Despite the inconsistencies, it appears from the literature that posture is an independent risk factor of modest magnitude for MSDs among computer users. It appears that lowering the height of the keyboard to or below the height of the elbow and resting the arms on the desk surface or chair armrests is associated with reduced risk of neck and shoulder MSDs. Results of epidemiological studies examining computer use (hours keying per day or per week) are more consistent than those examining posture, although some inconsistency is observed. Reasons for the inconsistency include possible selective survival bias resulting from cross-sectional study design, differences in exposure categorization, and possible interaction with other exposure variables. Overall, the literature shows that daily or weekly hours of computer use is more consistently associated with hand and arm MSDs than with neck and shoulder MSDs.

A prospective study of computer users: I. Study design and incidence of musculoskeletal symptoms and disorders.

BACKGROUND: A prospective study of computer users was performed to determine the occurrence of and evaluate risk factors for neck or shoulder (N/S) and hand or arm (H/A) musculoskeletal symptoms (MSS) and disorders (MSD). METHODS: Individuals (n = 632) newly hired into jobs requiring > or = 15 hr/week of computer use were followed for up to 3 years. At study entry, workstation dimensions and worker postures were measured and medical and psychosocial risk factors were assessed. Daily diaries were used to document work practices and incident MSS. Those reporting MSS were examined for specific MSD. Incidence rates of MSS and MSD were estimated with survival analysis. Cox regression models were used to evaluate associations between participant characteristics at entry and MSS and MSD. RESULTS: The annual incidence of N/S MSS was 58 cases/100 person-years and of N/S MSD was 35 cases/100 person-years. The most common N/S MSD was somatic pain syndrome. The annual incidence of H/A MSS was 39 cases/100 person-years and of H/A MSD was 21 cases/100 person-years. The most common H/A disorder was deQuervain's tendonitis. Forty-six percent of N/S and 32% of H/A MSS occurred during the first month of follow-up. Gender, age, ethnicity, and prior history of N/S pain were associated with N/S MSS and MSD. Gender, prior history of H/A pain, prior computer use, and children at home were associated with either H/A MSS or MSD. CONCLUSIONS: H/A and N/S MSS and MSD were common among computer users. More than 50% of computer users reported MSS during the first year after starting a new job.

A prospective study of computer users: II. Postural risk factors for musculoskeletal symptoms and disorders.

BACKGROUND: Despite widespread recommendations regarding posture during computer use, associations between specific postures and musculoskeletal health are not well characterized. METHODS: Six hundred and thirty-two newly hired computer users were followed prospectively to evaluate associations between posture and neck or shoulder (N/S) and hand or arm (H/A) musculoskeletal symptoms and musculoskeletal disorders. Participants' postures were measured at entry and they reported symptoms on weekly diaries. Participants reporting symptoms were examined for specific disorders. Multivariate Cox regression models were used to estimate associations between postural variables and risk of symptoms and disorders, controlling for confounding variables. RESULTS: Keying with an inner elbow angle > 121 degrees, greater downward head tilt, and presence of armrests on the participants chair were associated with lower risk of N/S symptoms or N/S disorders. Keying with elbow height below the height of the "J" key and the presence of a telephone shoulder rest were associated with a greater risk of N/S symptoms or N/S disorders. Horizontal location of the "J" key > 12 cm from the edge of the desk was associated with a lower risk of H/A symptoms and H/A disorders. Use of a keyboard with the "J" key > 3.5 cm above the table surface, key activation force > 48 g, and radial wrist deviation of > 5 degrees while using a mouse was associated with a greater risk of H/A symptoms or H/A disorders. The number of hours keying/week was associated with H/A symptoms and disorders. CONCLUSIONS: The results suggest that the risk of musculoskeletal symptoms and musculoskeletal disorders may be reduced by encouraging specific seated postures.