The role of community pharmacists in the prevention and management of osteoporosis and the risk of falls: results of a cross-sectional study and qualitative interviews.

UNLABELLED: In a mailed survey and qualitative interviews, it was observed that community pharmacists and public health authorities believe that pharmacists should play a significant role in the prevention and management of osteoporosis and the risk of falls. However, pharmacists acknowledge a wide gap between their ideal and actual levels of involvement. INTRODUCTION: The aim of this study was to explore perceptions of community pharmacists and public health authorities regarding the role of pharmacists in providing services in relation to osteoporosis and risk of falls and the barriers to providing them. METHODS: Using a modified five-step version of Dillman's tailored design method, a questionnaire was mailed to a random sample of 1,250 community pharmacists practicing in Montreal (Quebec, Canada) and surrounding areas. A similar questionnaire was sent to public health officers in these regions. Additionally, telephone interviews were conducted with regional and ministry level public health officers. RESULTS: Of the 1,250 pharmacists contacted, 28 were ineligible. In all, 571 of 1,222 (46.7 %) eligible community pharmacists and all the public health officers returned the questionnaire. Six public health officers (five regional and one at ministry level) were interviewed. Most pharmacists believed they should be involved in screening for osteoporosis (46.6 %) and risk of falls (50.3 %); however, fewer reported actually being involved in such services (17.4 % and 19.2 %, respectively). In their view, the main barriers to providing these services in current practice were lack of time (78.8 %), lack of clinical tools (65.4 %), and lack of coordination with other healthcare professionals (54.5 %). Public health authorities also thought community pharmacists should play a significant role in providing osteoporosis and fall risk services. However, few community pharmacist-mediated activities are in place in the participating regions. CONCLUSIONS: Although community pharmacists and public health authorities believe pharmacists should play a significant role with regard to osteoporosis and the risk of falls, they acknowledge a wide gap between the ideal and actual levels of pharmacist involvement.

Effectiveness of interventions to improve the detection and treatment of osteoporosis in primary care settings: a systematic review and meta-analysis.

This study aims to evaluate the effectiveness of primary care interventions to improve the detection and treatment of osteoporosis. Eight electronic databases and six gray literature sources were searched. Randomized controlled trials, controlled clinical trials, quasi-randomized trials, controlled before-after studies, and interrupted time series written in English or French from 1985 to 2009 were considered. Eligible studies had to include patients at risk (women ≥ 65 years, men ≥ 70 years, and men/women ≥ 50 years with at least one major risk factor for osteoporosis) or at high risk (men/women using oral glucocorticoids or with previous fragility fractures) for osteoporosis and fractures. Outcomes included bone mineral density (BMD) testing, osteoporosis treatment initiation, and fractures. Data were pooled using a random effects model when applicable. Thirteen studies were included. The majority were multifaceted and involved patient educational material, physician notification, and/or physician education. Absolute differences in the incidence of BMD testing ranged from 22% to 51% for high-risk patients only and from 4% to 18% for both at-risk and high-risk patients. Absolute differences in the incidence of osteoporosis treatment initiation ranged from 18% to 29% for high-risk patients only and from 2% to 4% for at-risk and high-risk patients. Pooling the results of six trials showed an increased incidence of osteoporosis treatment initiation (risk difference (RD) = 20%; 95% CI: 7-33%) and of BMD testing and/or osteoporosis treatment initiation (RD = 40%; 95% CI: 32-48%) for high-risk patients following intervention. Multifaceted interventions targeting high-risk patients and their primary care providers may improve the management of osteoporosis, but improvements are often clinically modest.

Exposure to anti-infective drugs during pregnancy and the risk of small-for-gestational-age newborns: a case-control study.

OBJECTIVE: To determine the association between anti-infective exposure during the last two trimesters of pregnancy and the risk of small-for-gestational-age (SGA) newborns. DESIGN: Case-control study within the Québec Pregnancy Registry. SETTING: Province of Québec, Canada. SAMPLE: Analyses were performed on prospectively collected data of 63,338 pregnant women that met eligibility criteria for the study (8192 cases and 55,146 controls). METHODS: Unconditional logistic regression models were used to quantify the association between exposure to anti-infective drugs and the risk of SGA. MAIN OUTCOME MEASURES: A case of SGA was defined as a pregnancy resulting in a baby that weighs below the tenth percentile, adjusted for gestational age and gender, according to the Canadian gender-specific reference curves. A control was defined as a pregnancy resulting in a baby that weighs greater or equal to the tenth percentile, adjusted for gestational age and gender. RESULTS: Exposure to all combined anti-infective drugs was not associated with the risk of SGA (OR 0.97; 95% CI 0.91-1.04). The use of sulfamethoxazole/trimethoprim was associated with SGA (OR 1.61; 95% CI 1.16-2.23), whereas the use of urinary anti-infective drugs decreased the risk (OR 0.80; 95% CI 0.65-0.97). CONCLUSIONS: Exposure to sulfamethoxazole/trimethoprim during the last two trimesters of pregnancy was associated with SGA. Further research is needed to address the use of other therapeutic alternatives in the management of infections that predispose infants being born SGA in pregnant women with other risk factors for this condition.

Impact of a primary care physician workshop on osteoporosis medical practices.

SUMMARY: Attendance at a fragility-fractures-prevention workshop by primary care physicians was associated with higher rates of osteoporosis screening and treatment initiation in elderly female patients and higher rates of treatment initiation in high-risk male and female patients. However, osteoporosis management remained sub-optimal, particularly in men. INTRODUCTION: Rates of osteoporosis-related medical practices of primary care physicians exposed to a fragility-fractures-prevention workshop were compared with those of unexposed physicians. METHODS: In a cluster cohort study, 26 physicians exposed to a workshop were matched with 260 unexposed physicians by sex and year of graduation. For each physician, rates of bone mineral density (BMD) testing and osteoporosis treatment initiation among his/her elderly patients 1 year following the workshop were computed. Rates were compared using multilevel logistic regression models controlling for potential patient- and physician-level confounders. RESULTS: Twenty-five exposed physicians (1,124 patients) and 209 unexposed physicians (9,663 patients) followed at least one eligible patient. In women, followed by exposed physicians, higher rates of BMD testing [8.5% versus 4.2%, adjusted OR (aOR) = 2.81, 95% CI 1.60-4.94] and treatment initiation with bone-specific drugs (BSDs; 4.8% vs. 2.4%, aOR = 1.95, 1.06-3.60) were observed. In men, no differences were detected. In patients on long-term glucocorticoid therapy or with a previous osteoporotic fracture, higher rates of treatment initiation with BSDs were observed in women (12.0% vs. 1.9%, aOR = 7.38, 1.55-35.26), and men were more likely to initiate calcium/vitamin D (5.3% vs. 0.8%, aOR = 7.14, 1.16-44.06). CONCLUSIONS: Attendance at a primary care physician workshop was associated with higher rates of osteoporosis medical practices for elderly women and high-risk men and women. However, osteoporosis detection and treatment remained sub-optimal, particularly in men.

Control and severity of asthma during pregnancy are associated with asthma incidence in offspring: two-stage case-control study.

The extent to which childhood asthma incidence is influenced by asthma control and severity during pregnancy is unknown. We have studied this association during the child's first 10 yrs of life. A two-stage, case-control study, nested in a cohort of 8,226 children of asthmatic mothers, was conducted using three interlinked databases of Quebec, Canada, and mailed questionnaires. A total of 2,681 asthmatic children and 30,318 age-matched controls were selected (< or =20 controls.case(-1); stage 1), and 3,254 selected mothers were mailed questionnaires to obtain additional information (stage 2). Asthma control and severity was defined using validated indexes and childhood asthma incidence based on at least one asthma-related diagnosis and prescription received within 2 yrs. A total of 44 confounders were considered. Compared with children of mild controlled asthmatic mothers, children whose mothers had moderate-to-severe uncontrolled asthma during pregnancy had an increased risk of asthma (adjusted OR 1.27, 95% CI 1.06-1.52). No increased risk was observed for children of mild uncontrolled and moderate-to-severe controlled mothers. Based on one of the largest studies of children of asthmatic mothers, a significant increase in asthma risk was demonstrated among children whose mothers had poor control and increased severity of asthma during pregnancy, indicating that this element should be added to the expanding list of determinants of childhood asthma. As it constitutes a risk factor where pregnant asthmatic females can intervene, it is of great importance for physicians to optimally treat asthmatic females during pregnancy and to encourage females to be adherent to the prescribed asthma medications.

Better adherence to antihypertensive agents and risk reduction of chronic heart failure.

AIMS: Antihypertensive (AH) agents have been shown to reduce the risk of major cardiovascular events including chronic heart failure (CHF). However, the impact of changes in patterns of AH agents use on CHF is unknown. Our objective was to estimate to which different patterns of AH agent use is associated with the occurrence of CHF in a population-based study. METHOD AND RESULTS: A cohort of 82 320 patients was reconstructed using the Régie de l'assurance maladie du Québec's databases. Patients were eligible if they were between 45 to 85 years of age, had no indication of cardiovascular disease and were newly treated with AH therapy between 1999 and 2004. A nested case-control design was used to study the occurrence of CHF. Every case of CHF was matched for age and duration of follow-up to a maximum of 15 randomly selected controls. Adherence level was reported as a medication possession ratio. Conditional logistic regression models were used to estimate the rate ratio (RR) of CHF adjusting for different covariables. The mean patient age was 65 years, 37% were male, 8% had diabetes, 19% had dyslipidaemia and mean time of follow-up at 2.7 years. High adherence level (95%) to AH therapy compared with lower adherence level (60%) was associated with an additional reduction of CHF events (RR: 0.89; 0.80-0.99). Risk factors for CHF were being on social assistance, diabetes, dyslipidaemia, higher chronic disease score and developing a cardiovascular condition during follow-up. CONCLUSION: Our study suggests that a better adherence is associated with a significant risk reduction of CHF. Adherence to AH therapy needs to be improved to optimize benefits.

Comparison of direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate: a population-based study.

UNLABELLED: This population-based study aimed to compare direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. During a 2-year follow-up period, compared to those with medication possession ratio (MPR) > or = 80%, women with MPR < 80% incurred significantly higher physician care costs and hospital care costs. INTRODUCTION: This study aimed to compare direct health care costs related to the treatment of osteoporosis and osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. METHODS: A cohort of 15,027 women having initiated alendronate or risedronate was identified. MPR and direct health care costs (physician care, hospital care, drugs) were assessed during a 2-year period. Regression models were used to estimate mean predicted cost for compliant (MPR > or = 80%) and noncompliant (MPR < 80%) women. RESULTS: Mean predicted physician care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among those with MPR > or = 80%: mean difference $17, 95% confidence interval (CI) $2-22. Mean predicted hospital care cost was $568 among women with MPR < 80% and $379 among those with MPR > or = 80%: mean difference $189, 95% CI $56-320. Mean predicted drug cost was $439 among women with MPR < 80% and $1,068 among those with MPR > or = 80%: mean difference $-639, 95% CI $-649 to -629. CONCLUSION: Compared to compliant women, noncompliant women incurred significantly higher physician care and hospital care costs. Due to lower drug costs, total direct health care costs were lower among noncompliant women.

MR Imaging-Based Radiomic Signatures of Distinct Molecular Subgroups of Medulloblastoma.

BACKGROUND AND PURPOSE: Distinct molecular subgroups of pediatric medulloblastoma confer important differences in prognosis and therapy. Currently, tissue sampling is the only method to obtain information for classification. Our goal was to develop and validate radiomic and machine learning approaches for predicting molecular subgroups of pediatric medulloblastoma. MATERIALS AND METHODS: In this multi-institutional retrospective study, we evaluated MR imaging datasets of 109 pediatric patients with medulloblastoma from 3 children's hospitals from January 2001 to January 2014. A computational framework was developed to extract MR imaging-based radiomic features from tumor segmentations, and we tested 2 predictive models: a double 10-fold cross-validation using a combined dataset consisting of all 3 patient cohorts and a 3-dataset cross-validation, in which training was performed on 2 cohorts and testing was performed on the third independent cohort. We used the Wilcoxon rank sum test for feature selection with assessment of area under the receiver operating characteristic curve to evaluate model performance. RESULTS: Of 590 MR imaging-derived radiomic features, including intensity-based histograms, tumor edge-sharpness, Gabor features, and local area integral invariant features, extracted from imaging-derived tumor segmentations, tumor edge-sharpness was most useful for predicting sonic hedgehog and group 4 tumors. Receiver operating characteristic analysis revealed superior performance of the double 10-fold cross-validation model for predicting sonic hedgehog, group 3, and group 4 tumors when using combined T1- and T2-weighted images (area under the curve = 0.79, 0.70, and 0.83, respectively). With the independent 3-dataset cross-validation strategy, select radiomic features were predictive of sonic hedgehog (area under the curve = 0.70-0.73) and group 4 (area under the curve = 0.76-0.80) medulloblastoma. CONCLUSIONS: This study provides proof-of-concept results for the application of radiomic and machine learning approaches to a multi-institutional dataset for the prediction of medulloblastoma subgroups.

Vitamin B12 Deficiency Induced by the Use of Gastric Acid Inhibitors: Calcium Supplements as a Potential Effect Modifier.

OBJECTIVE: Use of gastric acid inhibitors has emerged as a risk factor of vitamin B12 deficiency, especially in older adults. Calcium supplements could be an effect modifier of this relationship by its role in the absorption process of vitamin B12. The aim of this study is to examine whether the use of calcium supplements could be an effect modifier of the association between gastric acid inhibitors and vitamin B12 deficiency. DESIGN: Cross-sectional study based on medical chart reviews. SETTING: Geriatric Assessment Unit (GAU) of a university-affiliated hospital. PARTICIPANTS: The study included 172 patients discharged from the GAU between 2008 and 2012. MEASUREMENTS: Cases of vitamin B12 deficiency were identified as those who had received a diagnosis of vitamin B12 deficiency, and/or were receiving a treatment for vitamin B12 deficiency. Use of gastric acid inhibitors and calcium supplements at admission was determined from the pharmacist report. Associations between medications and vitamin B12 status were investigated using logistic regression models. RESULTS: Seventy-one patients (41%) had vitamin B12 deficiency. At admission, 42% were taking gastric acid inhibitors and 45% calcium supplements. After adjustment for covariates, analyses revealed that vitamin B12 deficiency was more likely among users of gastric acid inhibitors who did not concomitantly received calcium supplements [OR=3.12; P=0.01]. Conversely, no significant association was observed in patients using both, gastric acid inhibitors and calcium supplements [OR=1.30; P=0.59]. CONCLUSIONS: The present study provides the very first evidence that the use of calcium supplements could be an effect modifier of the association between gastric acid inhibitors and vitamin B12 deficiency. Failure to consider calcium supplements as an effect modifier could have led to biased risk estimates in previous published studies.

The use of basiliximab-infliximab combination for the treatment of severe gastrointestinal acute GvHD.

After allogeneic stem cell transplant, severe grade III-IV gastrointestinal (GI) acute GvHD is associated with significant morbidity and mortality, and generally results in poor outcomes. Salvage therapy for patients who fail steroid therapy is not well defined in the literature. In the current retrospective study, we reviewed our experience with the combination of basiliximab and infliximab in 21 patients with severe, grade III-IV GI acute GvHD of whom 16 met the definition for steroid-refractory disease. The overall response rate was 76%, with 43% CR at a median time of 21 days after beginning treatment. The survival at 1 year was 24%, with most deaths due to complications from GvHD and recurrence of primary disease. All five of the long-term survivors have chronic GvHD. On the basis of a review of the literature, this regimen does not seem to be significantly more effective than other strategies for severe GI GvHD and seems to be worse than the results reported for basiliximab alone. Future studies of single-agent basiliximab and newer agents are required.

Individual variation in the frequency of sperm aneuploidy in humans.

To examine interindividual differences in sperm chromosome aneuploidy, repeated semen specimens were obtained from a group of ten healthy men, aged 20-21 at the start of the study, and analyzed by multi-color fluorescence in situ hybridization (FISH) analysis to determine the frequencies of sperm aneuploidy for chromosomes X, Y, 8, 18 and 21 and of diploidy. Semen samples were obtained three times over a five-year period. Statistical analysis examining the stability of sperm aneuploidy over time by type and chromosome identified two men who consistently exhibited elevated frequencies of sperm aneuploidy (stable variants): one with elevated disomy 18 and one with elevated MII diploidy. Differences among frequencies of aneuploidy by chromosome were also seen. Overall, disomy frequencies were lower for chromosome X, 8 and 18 than for chromosomes 21 or Y and for XY aneuploidy. The frequency of chromosome Y disomy did not differ from XY sperm frequency. Also, the frequency of meiosis I (XY) and II (YY + XX) sex chromosome errors did not differ in haploid sperm, but the frequency of MII errors was lower than MI errors in diploid sperm. Frequencies of sperm aneuploidy were similar between the first sampling period and the second, two years later. However, the frequency of some types of aneuploidy (XY, disomy Y, disomy 8, total autosomal disomies, total diploidy, and subcategories of diploidy) increased significantly between the first sampling period and the last, five years later, while others remained unchanged (disomy X, 21 and 18). These findings confirm inter-chromosome differences in the frequencies of disomy and suggest that some apparently healthy men exhibit consistently elevated frequencies of specific sperm aneuplodies. Furthermore, time/age-related changes in sperm aneuploidy may be detected over as short a period as five years in a repeated-measures study.

Treating hyperlipidemia for the primary prevention of coronary disease. Are higher dosages of lovastatin cost-effective?

OBJECTIVE: To compare the average and marginal life-time cost-effectiveness of increasing dosages of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, for the primary prevention of coronary heart disease (CHD). METHODS: We estimated the lifelong costs and benefits of the modification of lipid levels achieved with lovastatin based on published studies and a validated CHD prevention computer model. Patients were middle-aged men and women without CHD, with mean total serum cholesterol levels of 6.67, 7.84, and 9.90 mmol/L (258, 303, and 383 mg/dL), and high-density lipoprotein cholesterol levels of 1.19 mmol/L (46 mg/dL), as described in clinical trials. We estimated the cost per year of life saved for dosages of lovastatin ranging from 20 to 80 mg/d that reduced the total cholesterol level between 17% and 34%, and increased high-density lipoprotein cholesterol level between 4% and 13%. RESULTS: After discounting benefits and costs by 5% annually, the average cost-effectiveness of lovastatin, 20 mg/d, ranged from $11,040 to $52,463 for men and women. The marginal cost-effectiveness of 40 mg/d vs 20 mg/d remained in this range ($25,711 to $60,778) only for persons with baseline total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, the marginal cost-effectiveness of lovastatin, 80 mg/d vs 40 mg/d, was prohibitively expensive ($99,233 to $716,433 per year of life saved) for men and women, irrespective of the baseline total cholesterol level. CONCLUSIONS: Assuming that $50,000 per year of life saved is an acceptable cost-effectiveness ratio, treatment with lovastatin at a dosage of 20 mg/d is cost-effective for middle-aged men and women with baseline total cholesterol levels of 6.67 mmol/L (258 mg/dL) or higher. At current drug prices, treatment with 40 mg/d is also cost-effective for total cholesterol levels of 7.84 mmol/L (303 mg/dL) or higher. However, treatment with 80 mg/d is not cost-effective for primary prevention of CHD.

Patterns of oral anticoagulants use in atrial fibrillation.

BACKGROUND: Novel oral anticoagulants are available for the management of atrial fibrillation and are considered more convenient to use than warfarin. OBJECTIVE: The main objective of this study was to describe patterns of oral anticoagulant use in the 6 months period following the availability of dabigatran at our hospital. METHODS: A cross-sectional study was conducted in a single University hospital in the province of Québec, Canada. Medical records of subjects on oral anticoagulants for atrial fibrillation that were hospitalized between October 1st, 2011 and March 31th, 2012 were reviewed. Type of use (prevalent, incident and switch) and patient's characteristics of warfarin and dabigatran users were compared using Chi-squared and T-tests. RESULTS: In the 6-month period following dabigatran availability in the hospital, 59 patients (13%) were on dabigatran and 388 (87%) on warfarin. Mean CHADS2 score, mean age and mean number of chronic medications were lower in the dabigatran group. The percentage of patients with coronary artery disease was lower and renal function was higher in the dabigatran group. CONCLUSION: Dabigatran use remained low in the first 6 months period following the approval of dabigatran at our hospital, which could be explained by limited data on the efficacy and safety of this agent in subjects with multiple comorbidities.

Semen quality and reproductive health of young Czech men exposed to seasonal air pollution.

This study of male reproductive health in the Czech Republic resulted from community concern about potential adverse effects of air pollution. We compared young men (18 years of age) living in Teplice, a highly industrialized district with seasonally elevated levels of air pollution, to those from Prachatice, a rural district with relatively clean air. Surveys were scheduled for either late winter, after the season of higher air pollution, or at the end of summer, when pollution was low. Participation included a physical examination, donation of a semen sample, and completion of a questionnaire on health, personal habits, and exposure to solvents and metals through work or hobby. Analysis of data from 408 volunteers showed that the men from Teplice and Prachatice were similar in physical characteristics, personal habits, and work- or hobby-related exposures. Sixty-six percent (272) of these men donated a single semen sample for routine semen analysis, computer-aided sperm motion analysis, and sperm chromatin structure assay. The mean (median) sperm concentration and sperm count were 61. 2 (44.0) million/mL semen and 113.3 (81.5) million, respectively, and were not associated with district of residence or period of elevated air pollution. However, periods of elevated air pollution in Teplice were significantly associated with decrements in other semen measures including proportionately fewer motile sperm, proportionately fewer sperm with normal morphology or normal head shape, and proportionately more sperm with abnormal chromatin. These results suggest that young men may experience alterations in sperm quality after exposure to periods of elevated air pollution, without changes in sperm numbers.

Exposure to hazardous substances and male reproductive health: a research framework.

The discovery in the mid-1970s that occupational exposures to pesticides could diminish or destroy the fertility of workers sparked concern about the effects of hazardous substances on male reproductive health. More recently, there is evidence that sperm quantity and quality may have declined worldwide, that the incidence of testicular cancer has progressively increased in many countries, and that other disorders of the male reproductive tract such as hypospadias and cryptorchidism may have also increased. There is growing concern that occupational factors and environmental chemical exposures, including in utero and childhood exposures to compounds with estrogenic activity, may be correlated with these observed changes in male reproductive health and fertility. We review the evidence and methodologies that have contributed to our current understanding of environmental effects on male reproductive health and fertility and discuss the methodologic issues which confront investigators in this area. One of the greatest challenges confronting researchers in this area is assessing and comparing results from existing studies. We elaborate recommendations for future research. Researchers in the field of male reproductive health should continue working to prioritize hazardous substances; elucidate the magnitude of male reproductive health effects, particularly in the areas of testicular cancer, hypospadias, and cryptorchidism; develop biomarkers of exposure to reproductive toxins and of reproductive health effects for research and clinical use; foster collaborative interdisciplinary research; and recognize the importance of standardized laboratory methods and sample archiving.

Teplice program--the impact of air pollution on human health.

The aim of the Teplice Program is to investigate and assess the impact of air pollution on the health of the population in the district of Teplice, Czech Republic. Characterization of the air pollutants demonstrated unusually high concentrations during winter inversions of fine particles dominated by acidic sulfates, genotoxic organic compounds, and toxic trace elements. The major source of airborne fine particles is the burning of coal for heating and power. Human exposure and biomarker studies demonstrated large seasonal variations in air pollution within the Teplice District and higher seasonal average pollution levels than the comparative district, Prachatice. Personal exposures to fine particles and organic carcinogens [e.g., polycyclic aromatic hydrocarbons (PAH)] were correlated with excretion of PAH metabolites in urine, several trace metals in blood, and DNA adducts in white blood cells. Respiratory and neurobehavioral studies of school children were conducted using questionnaires and clinical measures. A significantly higher prevalence of adverse respiratory symptoms and decreased lung function were found in the Teplice district than in Prachatice. The neurobehavioral studies indicated significantly higher teacher referrals for clinical assessment in Teplice, but the majority of objective performance measures did not differ. Reproductive studies were conducted in both males and females. A study of the effects of exposure on pregnancy and birth found an excess prevalence of low birth weight and premature births in Teplice; these adverse effects were more common in infants conceived in the winter and whose mothers were smokers. Based on questionnaires and medical examination, the reproductive development of young men was not different between districts and seasons, however, measures of semen quality suggest that exposure to high levels of air pollution are associated with transient decrements in semen quality.

Workshop to identify critical windows of exposure for children's health: reproductive health in children and adolescents work group summary.

This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied. Prioritized research needs include basic studies on the cellular-molecular and endocrine regulation of sexual differentiation and development; increased efforts regarding potential adverse effects on development in females, including breast development; expanded animal studies on different classes of chemicals, comparing responses during development (prenatal and postnatal) with responses in adults; and, more extensive explorations regarding the reproductive biology and toxicology of puberty in humans.

Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis.

OBJECTIVE: Two identical 24-week, double-blind, placebo-controlled trials of tobramycin solution for inhalation (TOBI [PathoGenesis Corporation, Seattle, Washington]) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States. The aim of the present study was to extrapolate the US trial data to a Canadian setting, using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces. BACKGROUND: Cystic fibrosis is a genetic disease in which persistent respiratory infection, usually due to P. aeruginosa infection, is the major cause of morbidity and mortality. METHODS: The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results, reduced sputum levels of P. aeruginosa, and resulted in a 26% reduction in the probability of hospitalization (95% CI, 2%-43% vs placebo in the clinical trials). Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy. To adjust for Canadian pricing, pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries. Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation. RESULTS: Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs (in Canadian dollars) of $4055 in Ontario and $4916 in Quebec, which would substantially offset the Canadian acquisition price of $8602 for the same 24-week period. CONCLUSIONS: Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting, use of TOBI would reduce the use of health care services, particularly hospital days, and lead to substantial savings in direct medical costs that would offset its acquisition price. Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation.

Variability in the human-hamster in vitro assay for fertility evaluation.

Sources of variability in the zona-free hamster egg penetration assay were evaluated. Internal consistency in the assay was examined in replicate experiments using sperm from 23 donors. The average difference in the percentage of fertilization between the replicates was 3.9%. Optimal preincubation conditions and insemination time were examined and shown to be 0.5 to 1.0 X 10(7) sperm/ml and 2 to 3 hours. Abstinence time was found to be a variable, and a critical abstinence of more than 12 hours was required. Prolonged exposure to seminal plasma (i.e., more than 30 minutes) produced a reduction in the fertilization test results. If the variables studied here are consistently controlled, then changes in the assay results greater than the experimental error should reflect true changes in the semen sample.

Smoking cigarettes is associated with increased sperm disomy in teenage men.

OBJECTIVE: To determine whether moderate cigarette smoking and alcohol consumption in teenage men is associated with increases in disomic sperm and detectable changes in semen quality. DESIGN: Cohort study. SETTING: Military recruiting station, Teplice, Czech Republic. PATIENT(S): Ten current smokers (20 cigarettes per day for at least 2 years, exposure confirmed by urine cotinine) who also consumed alcohol and 15 nonsmokers. All patients were exactly 18 years old, healthy, and of unproven fertility. MAIN OUTCOME MEASURE(S): Sperm aneuploidy by multicolor fluorescence in situ hybridization for chromosomes 8, X, and Y; conventional semen analyses; computer-aided sperm analysis for motility; and sperm chromatin structure analysis. RESULTS: Smokers showed elevated frequencies of sperm aneuploidy (Y disomy, P <0.001; aggregate of X, Y, and 8 disomies, P <0.01); reduced linearity of sperm motion (P <0.05); and more "round-headed" sperm (P <0.01). Smokers' semen contained fewer sperm (P <0.001) and fewer motile sperm (P <0.02), which was attributable, in part, to shorter abstinence intervals among smokers (P <0.02). CONCLUSION(S): Cigarette smoking among teenagers was associated with increases in disomic sperm and a diminution in specific aspects of semen quality. Such defects may affect male fertility and may increase future chances of fathering offspring with aneuploidy syndromes.