Comparison of National Factor-based Models for Preeclampsia Screening.

OBJECTIVE: This study aimed to compare the predictive values of the American College of Obstetricians and Gynecologists (ACOG), the National Institute for Health and Care Excellence (NICE), and the Society of Obstetricians and Gynecologists of Canada (SOGC) factor-based models for preeclampsia (PE) screening. STUDY DESIGN: We conducted a secondary analysis of maternal and birth data from 32 hospitals. For each delivery, we calculated the risk of PE according to the ACOG, the NICE, and the SOGC models. Our primary outcomes were PE and preterm PE (PE combined with preterm birth) using the ACOG criteria. We calculated the detection rate (DR or sensitivity), the false positive rate (FPR or 1 - specificity), the positive (PPV) and negative (NPV) predictive values of each model for PE and for preterm PE using receiver operator characteristic (ROC) curves. RESULTS: We used 130,939 deliveries including 4,635 (3.5%) cases of PE and 823 (0.6%) cases of preterm PE. The ACOG model had a DR of 43.6% for PE and 50.3% for preterm PE with FPR of 15.6%; the NICE model had a DR of 36.2% for PE and 41.3% for preterm PE with FPR of 12.8%; and the SOGC model had a DR of 49.1% for PE and 51.6% for preterm PE with FPR of 22.2%. The PPV for PE of the ACOG (9.3%) and NICE (9.4%) models were both superior than the SOGC model (7.6%; p < 0.001), with a similar trend for the PPV for preterm PE (1.9 vs. 1.9 vs. 1.4%, respectively; p < 0.01). The area under the ROC curves suggested that the ACOG model is superior to the NICE for the prediction of PE and preterm PE and superior to the SOGC models for the prediction of preterm PE (all with p < 0.001). CONCLUSION: The current ACOG factor-based model for the prediction of PE and preterm PE, without considering race, is superior to the NICE and SOGC models. KEY POINTS: · Clinical factor-based model can predict PE in approximately 44% of the cases for a 16% false positive.. · The ACOG model is superior to the NICE and SOGC models to predict PE.. · Clinical factor-based models are better to predict PE in parous than in nulliparous..

Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Impact of Audits and Multifaceted Intervention on Vaginal Birth After Caesarean: Secondary Analysis of the QUARISMA Trial.

OBJECTIVES: This study estimated the effect that a multifaceted intervention aiming to improve the quality of obstetrical care and reduce Caesarean section (CS) had on the rate of vaginal birth after Caesarean (VBAC). METHODS: This is a secondary analysis of the cluster randomized controlled trial Quality of Care, Obstetrics Risk Management, and Mode of Delivery involving (1) audits regarding the indications for CS, (2) provision of feedback to health professionals, and (3) implementation of best practices to reduce CS rates in Quebec. The impact of intervention on VBAC, trial of labour (TOL), and maternal and neonatal morbidity was reported using adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Out of 105 351 women who delivered during the pre- and postintervention period, 12 493 (11.9%) had a previous CS. We observed no significant impact of the multifaceted intervention on the rates of TOL (adjusted OR 1.22; 95% CI 0.96-1.56, P = 0.11) and VBAC (adjusted OR 1.20; 95% CI 0.97-1.48, P = 0.10) in women with one previous CS. However, the rate of TOL was reduced (adjusted OR 0.38; 95% CI 0.14-0.99) in women with more than one previous CS. The intervention has no influence on maternal and neonatal morbidity. CONCLUSIONS: A multifaceted intervention including audits, feedback to health professionals, and implementation of best practices did not affect VBAC rates or maternal and neonatal morbidity. Our results pointed out the need for decision-making processand risk management tools specific to women with previous CS.

Reporting Caesarean Delivery in Quebec Using the Robson Classification System.

OBJECTIVE: The increasing rates of Caesarean sections throughout the world is preoccupant, and a good understanding of which groups of women contribute the most to the CS rate represents an important question in public health. Therefore, we sought to report the CS rate according to the Robson's classification system in the Quebec population. METHOD: We performed a secondary analysis of the QUARISMA database, including all deliveries after 24 weeks' gestation from 32 maternity wards in the province of Quebec between 2008 and 2011 (n = 184 952 deliveries). CS rates were reported according to the modified Robson criteria from The Society of Obstetricians and Gynaecologists of Canada with the relative contribution to the total number of CSs. RESULTS: We observed a global CS rate of 22.9%. Women with previous CS and a fetus in cephalic presentation at term accounted for 35% of all Caesarean deliveries. Nulliparous women with cephalic presentation at term accounted for 30% of all CSs. Among nulliparous women with cephalic presentation, women with spontaneous labour contributed to 12% of all CSs, whereas women with an induction of labour contributed to 16% of all CSs. Non-cephalic fetal presentation accounted for 19% of all CSs. Other indications accounted for the remaining 16% of CSs. CONCLUSION: Most CSs are performed for multiparous women with previous CS; nulliparous women with a cephalic presentation at term, especially those undergoing labour induction; and non-cephalic fetal presentation.

Prognosis Driven Rehabilitation After Rotator Cuff Repair Surgery.

BACKGROUND: Rehabilitation after rotator cuff repair surgery has been the focus of several clinical trials in the past decade. Many illuminate new evidence with regard to the prognosis of structural and functional success after surgery. METHODS: A selective literature search was performed and personal physiotherapeutic and surgical experiences are reported. RESULTS: Post-operative rehabilitation parameters, namely the decision to delay or allow early range of motion after surgery, play a large role in the overall success after surgery. Using a prognosis driven rehabilitation program offers clinicians a means of prescribing optimal rehabilitation parameters while ensuring structural and functional success. This commentary aims to synthesize the evidence in a spectrum of prognostic factors to guide post-operative rehabilitation. CONCLUSION: The optimal rehabilitation program after rotator cuff repair surgery is debatable; therefore, we suggest using a spectrum of prognostic factors to determine a rehabilitation program suited to ensure structural and functional success, quickly and safely.

Predicting Perinatal Outcome from Prenatal Ultrasound Characteristics in Pregnancies Complicated by Gastroschisis.

INTRODUCTION: The objective of the study was to establish the predictive value of prenatal ultrasound markers for complex gastroschisis (GS) in the first 10 days of life. MATERIAL AND METHODS: In this retrospective cohort study over 11 years (2000-2011) of 117 GS cases, the following prenatal ultrasound signs were analyzed at the last second- and third-trimester ultrasounds: intrauterine growth restriction, intra-abdominal bowel dilatation (IABD) adjusted for gestational age, extra-abdominal bowel dilatation (EABD) ≥25 mm, stomach dilatation, stomach herniation, perturbed mesenteric circulation, absence of bowel lumen and echogenic dilated bowel loops (EDBL). RESULTS: Among 114 live births, 16 newborns had complex GS (14.0%). Death was seen in 16 cases (13.7%): 3 intrauterine fetal deaths, 9 complex GS and 4 simple GS. Second-trimester markers had limited predictive value. Third-trimester IABD, EABD, EDBL, absence of intestinal lumen and perturbed mesenteric circulation were statistically associated with complex GS and death. IABD was able to predict complex GS with a sensitivity of 50%, a specificity of 91%, a positive predictive value of 47% and a negative predictive value of 92%. DISCUSSION: Third-trimester IABD adjusted for gestational age appears to be the prenatal ultrasound marker most strongly associated with adverse outcome in GS.

A cluster-randomized trial to reduce cesarean delivery rates in Quebec.

BACKGROUND: In Canada, cesarean delivery rates have increased substantially over the past decade. Effective, safe strategies are needed to reduce these rates. METHODS: We conducted a cluster-randomized, controlled trial of a multifaceted 1.5-year intervention at 32 hospitals in Quebec. The intervention involved audits of indications for cesarean delivery, provision of feedback to health professionals, and implementation of best practices. The primary outcome was the cesarean delivery rate in the 1-year postintervention period. RESULTS: Among the 184,952 participants, 53,086 women delivered in the year before the intervention and 52,265 women delivered in the year following the intervention. There was a significant but small reduction in the rate of cesarean delivery from the preintervention period to the postintervention period in the intervention group as compared with the control group (change, 22.5% to 21.8% in the intervention group and 23.2% to 23.5% in the control group; odds ratio for incremental change over time, adjusted for hospital and patient characteristics, 0.90; 95% confidence interval [CI], 0.80 to 0.99; P=0.04; adjusted risk difference, -1.8%; 95% CI, -3.8 to -0.2). The cesarean delivery rate was significantly reduced among women with low-risk pregnancies (adjusted risk difference, -1.7%; 95% CI, -3.0 to -0.3; P=0.03) but not among those with high-risk pregnancies (P=0.35; P = 0.03 for interaction). The intervention group also had a reduction in major neonatal morbidity as compared with the control group (adjusted risk difference, -0.7%; 95% CI, -1.3 to -0.1; P=0.03) and a smaller increase in minor neonatal morbidity (adjusted risk difference, -1.7%; 95% CI, -2.6 to -0.9; P<0.001). Changes in minor and major maternal morbidity did not differ significantly between the groups. CONCLUSIONS: Audits of indications for cesarean delivery, feedback for health professionals, and implementation of best practices, as compared with usual care, resulted in a significant but small reduction in the rate of cesarean delivery, without adverse effects on maternal or neonatal outcomes. The benefit was driven by the effect of the intervention in low-risk pregnancies. (Funded by the Canadian Institutes of Health Research; QUARISMA Current Controlled Trials number, ISRCTN95086407.).

Outreach strategies for the promotion of HIV testing and care: closing the gap between health services and female sex workers in Benin.

BACKGROUND: Regular voluntary counseling and testing is a key component of the fight against HIV/AIDS. In Benin, the project SIDA-1/2/3 established to decrease HIV/sexually transmitted infection (STIs) among female sex workers (FSWs), implemented a multifaceted intervention, including outreach activities. The objective of this article was to present potential advantages and limitations of 3 categories of outreach interventions designed to increase the use of testing services among FSWs in Benin. METHODS: This analysis is based on ethnographic fieldwork conducted in Benin from June to December 2012. RESULTS: Sixty-six FSWs and 24 health care workers were interviewed. Their narratives revealed 3 main factors impeding the development of appropriate HIV testing behavior. These negative elements can be positioned along a continuum of health care behaviors, with each stage of this continuum presenting its own challenges: fear or lack of motivation to use testing services, inaccessibility of care when the decision to go has been made, and a perceived lack of quality in the care offered at the health care center. Many of these needs seem to be addressed in the outreach strategies tested. However, the study also exposed some potential barriers or limitations to the success of these strategies when applied in this specific context, due to social disruption, mobility, access to care, and hard to reach population. CONCLUSIONS: To increase the use of testing services, an outreach strategy based on community workers or peer educators, along with improved access to testing services, would be well adapted to this context and appreciated by both FSWs and health care workers.

Validation of a prediction model for vaginal birth after caesarean.

BACKGROUND: Pregnant women with a previous Caesarean section face making the decision to undergo an elective repeat Caesarean section or to attempt a trial of labour with the goal of achieving a vaginal birth after Caesarean (VBAC). One of the key factors in counselling these women is the probability of a successful VBAC. We aimed to validate a prediction model for VBAC success. METHODS: We performed an analysis of women at term with one prior low-transverse Caesarean section and a live cephalic singleton pregnancy who attempted a trial of labour after Caesarean (TOLAC) at 32 hospitals in Quebec between 2008 and 2012. The individual TOLAC probabilities of success were calculated without regard to ethnicity, using a prediction model previously developed in the United States. The predictive ability of the model was assessed using receiver operating characteristic curves and the area under the curve (AUC). In addition, a calibration curve was generated by plotting the predicted and observed VBAC rates. RESULTS: Of 3113 eligible women who underwent TOLAC, we found an overall rate of VBAC of 75.3%. Beyond a predicted probability of 40%, both observed and predicted TOLAC success rates were similar. The accuracy of the model was high (AUC = 0.72; 95% CI 0.70 to 0.74, P < 0.001) as was the correlation between observed and predicted probabilities of TOLAC success (R² = 0.98). Finally, for women requiring induction of labour, observed and predicted probabilities were similar for a predicted probability ≥ 70%. CONCLUSION: It is possible to estimate VBAC success accurately in Quebec using a validated prediction model from the United States. This model may be used in practice without regard to ethnicity as a primary method to refine counselling during antepartum visits for women with a prior Caesarean section.

Validation of a prediction model for predicting the probability of morbidity related to a trial of labour in Quebec.

BACKGROUND: Pregnant women with a history of previous Caesarean section face the decision either to undergo an elective repeat Caesarean section (ERCS) or to attempt a trial of labour with the goal of achieving a vaginal birth after Caesarean (VBAC). Both choices are associated with their own risks of maternal and neonatal morbidity. We aimed to determine the external validity of a prediction model for the success of trial of labour after Caesarean section (TOLAC) that could help these women in their decision-making. METHODS: We used a perinatal database including 185,437 deliveries from 32 obstetrical centres in Quebec between 2007 and 2011 and selected women with one previous Caesarean section who were eligible for a TOLAC. We compared the frequency of maternal and neonatal morbidity between women who underwent TOLAC and those who underwent an ERCS according to the probability of success of TOLAC calculated from a published model of prediction. RESULTS: Of 8508 eligible women, including 3113 who underwent TOLAC, both maternal and neonatal morbidities became less frequent as the predicted chance of VBAC increased (P < 0.05). Women undergoing a TOLAC were more likely to have maternal morbidity than those who underwent an ERCS when the predicted probability of VBAC was less than 60% (relative risk [RR] 2.3; 95% CI 1.4 to 4.0); conversely, maternal morbidity was not different between the two groups when the predicted probability of VBAC was at least 60% (RR 0.8; 95% CI 0.6 to 1.1). Neonatal morbidity was similar between groups when the probability of VBAC success was 70% or greater (RR 1.2; 95% CI 0.9 to 1.5). CONCLUSION: The use of a prediction model for TOLAC success could be useful in the prediction of TOLAC success and perinatal morbidity in a Canadian population. Neither maternal nor neonatal morbidity are increased with a TOLAC when the probability of VBAC success is at least 70%.

Decision aid tools to support women's decision making in pregnancy and birth: a systematic review and meta-analysis.

Support for a model of shared medical decision making, where women and their care providers discuss risks and benefits of their different options, reveal their preferences, and jointly make a decision, is a growing expectation in obstetric care. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of different decision aid tools compared to regular care for women facing several options in the specific field of obstetric care. We included published studies about interventions designed to aid mothers' decision making and provide information about obstetrical treatment or screening options. Following a search of electronic databases for articles published in English and French from 1994 to 2010, we found ten studies that met the inclusion criteria. In this systematic review and meta-analysis we found that all decision aid tools, except for Decision Trees, facilitated significant increases in knowledge. The Computer-based Information Tool, the Decision Analysis Tools, Individual Counseling and Group Counseling intervention presented significant results in reducing anxiety levels. The Decision Analysis Tools and the Computer-based Information tool were associated with a reduction in levels of decisional conflict. The Decision Analysis Tool was the only tool that presented evidence of an impact on the final choice and final outcome. Decision aid tools can assist health professionals to provide information and counseling about choices during pregnancy and support women in shared decision making. The choice of a specific tool should depend on resources available to support their use as well as the specific decisions being faced by women, their health care setting and providers.

Portrait of a lengthy vaccination trajectory in Burkina Faso: from cultural acceptance of vaccines to actual immunization.

BACKGROUND: The global recognition of vaccination is strongly related to the fact that it has proved in the past able to dramatically reduce the incidence of certain diseases. Nevertheless, reactions regarding the practice of vaccination still vary among communities, affecting the worldwide vaccination coverage. Numerous studies, conducted from varying perspectives, have focused on explaining this active refusal or resistance to vaccination. Although in some cases low immunization coverage has been well explained by active refusal or resistance to vaccination, little is known about the reasons for low coverage where those reactions are absent or play a minor role, especially outside an epidemic context. This study attempts to explain this situation, which is found in the health district of Nouna in Burkina Faso. METHODS: An in-depth ethnographic study was undertaken in the health district of Nouna in an effort to understand, from an anthropological point of view, the logic behind the parental decision-making process regarding the vaccination or non-vaccination of children, in a context where rejection of, and reservations concerning vaccination are not major obstacles. RESULTS: Three elements emerged from the analysis: the empirical conceptions of childhood diseases, the perceived efficacy of vaccine and the knowledge of appropriate age for vaccination uptake; the gap between the decision-making process and the actual achievement of vaccination; and the vaccination procedure leading to vaccination uptake in the particular context of the health district of Nouna. CONCLUSION: The procedures parents must follow in order to obtain vaccination for their children appear complex and constraining, and on certain points discord with the traditional systems of meaning and idioms of distress related to pregnancy, the prevention of childhood diseases and with the cultural matrix shaping decision-making and behaviour. Attention needs to be directed at certain promotional, logistical and structural elements, and at the procedure that must currently be followed to obtain vaccination for a child during routine vaccination sessions, which are currently limiting the active demand for vaccination. ABSTRACT IN FRENCH : See the full article online for a translation of this abstract in French.

Translating malaria as sumaya: Justified convention or inappropriateness?

In exchanges between health professionals and consultants in the West African context, the word malaria is often replaced by its equivalent in the local dialect. In the Nouna health district of Burkina Faso the term malaria is regularly translated as sumaya. Acknowledging that there may be important epistemological differences between malaria, a term issued from the biomedical epistemology, and sumaya, which is borrowed from traditional medicine epistemology, the possible mismatches between these two terms have been assessed to anticipate problems that may result from their translation by different health stakeholders. By consulting various traditional healers and other members of the communities about the local meaning of the term sumaya, it has been possible to compare the conceptualisation of sumaya to the biomedical conceptualisation of malaria and assess the gap between them. An investigation based on a sample of 13 traditional healers and over 450 individuals from Nouna's health district was conducted to document the meaning of the term sumaya. This paper demonstrates that the generally accepted translation of the word malaria as sumaya is a mistake when one looks at the different systems of belief and representations given to each of these two terms.

[Evaluation of transfer of knowledge about malaria by health professionals to patients' mothers in Nouna, Burkina Faso]. / Enquête sur le transfert de connaissances concernant le paludisme par les professionnels de la santé aux consultants dans la région de Nouna au Burkina Faso.

To reduce the infant mortality rate associated with malaria, the WHO recommends preventive home treatment by antimalarial drugs for all children with fever. This practice requires some medical knowledge by mothers who want to treat their children. In Burkina Faso, the main source of the transmission of such knowledge and skills is the interaction between health professionals and mothers during consultations for their children. The main objective of this study was to assess the transfer of knowledge by health professionals to mothers about the causes, symptoms and treatment of malaria in the health district of Nouna, in the province of Kossi, Burkina Faso. The results showed that at the time of the interview very few mothers were able to recognize malaria and treat it adequately. Mothers' lack of malaria-related knowledge and skills was quite substantial and even more pronounced in the sample of mothers from villages. Many did not know the exact cause of malaria or how to treat it. In view of the factors that must be taken into account for the successful treatment of malaria at home (appropriate dose for age, appropriate duration of treatment, appropriate, i.e.,antimalarial, drugs, quality of drugs) it is estimated that only 3.5% of all interviewed mothers had the knowledge necessary to treat malaria correctly at home. Health professionals appeared to agree that the mothers lacked these skills, but our data revealed that they did not provide information to the mothers to address this lack. Specifically, they did not routinely provide information about prevention by mosquito nets, diagnosis based on key symptoms such as fever, the importance of rapid consultation, rules for antimalarial dosing according to age, the risks of under-medication or the dangers related to the purchase and consumption of street drugs that may be counterfeit or have expired.

Identifying barriers and facilitators towards implementing guidelines to reduce caesarean section rates in Quebec.

OBJECTIVE: To investigate obstetricians perceptions of clinical practice guidelines targeting management of labour and vaginal birth after previous caesarean birth, and to identify the barriers to, facilitators of and obstetricians solutions for implementing these guidelines in practice. METHODS: This qualitative study was conducted in three hospitals in Montreal that represent around 10% of births in Quebec. Data was collected from 10 focus groups, followed by six semi-structured interviews. Two researchers jointly analysed the verbatim transcripts according to A manual for the use of focus groups. FINDINGS: The identified barriers to and facilitators of the implementation of guidelines can be classified into four categories: 1) the hospital level, including management and hospital policies; 2) the departmental level, including local policies, leadership, organizational factors, economic incentive, and availability of equipment and staff; 3) the health professionals motivations and attitudes, including medico-legal concerns, skill levels, acceptance of guidelines and strategies used to implement recommendations; and 4) patients motivations. CONCLUSION: Identifying the barriers to and facilitators of the adoption of recommendations is an important way to guide the development of efficient strategies. The findings of this study suggest that the adoption of guidelines may be improved if local health professionals perceptions are considered to make recommendations more acceptable and useful. Our findings also support the assumption that obstetricians seek to implement best practices, but require evidence tools and support to assess their practices and enhance their performance. In addition, peer review activities championed by opinion leaders have been identified by obstetricians as the most suitable strategy to improve the use of the guidelines in their practices.

Evidence-based strategies for implementing guidelines in obstetrics: a systematic review.

OBJECTIVE: To estimate effective strategies for implementing clinical practice guidelines in obstetric care and to identify specific barriers to behavior change and facilitators in obstetrics. DATA SOURCES: The Cochrane Library, EMBASE, and MEDLINE were consulted from January 1990 to June 2005. Additional studies were identified by screening reference lists from identified studies and experts' suggestions. METHODS OF STUDY SELECTION: Studies of clinical practice guidelines implementation strategies in obstetric care and reviews of such studies were selected. Randomized controlled trials, controlled before-after studies, and interrupted time series studies were evaluated according to Effective Practice and Organization of Care criteria standards. TABULATION, INTEGRATION, AND RESULTS: Studies were reviewed by two investigators to assess the quality and the efficacy of each strategy. Discordances between the two reviewers were resolved by consensus. In obstetrics, educational strategies with medical providers are generally ineffective; educational strategies with paramedical providers, opinion leaders, qualitative improvement, and academic detailing have mixed effects; audit and feedback, reminders, and multifaceted strategies are generally effective. These findings differ from data on the efficacy of clinical practice guidelines implementation strategies in other medical specialties. Specific barriers to behavior change in obstetrics and methods to overcome these barriers could explain these differences. The proportion of effective strategies is significantly higher among the interventions that include a prospective identification of barriers to change compared with standardized interventions. CONCLUSION: Prospective identification of efficient strategies and barriers to change is necessary to achieve a better adaptation of intervention and to improve clinical practice guidelines implementation. In the field of obstetric care, multifaceted strategy based on audit and feedback and facilitated by local opinion leaders is recommended to effectively change behaviors.

Arsenic toxicity at low doses: epidemiological and mode of action considerations.

Current approaches to risk assessment typically assume a linear dose-response for mutagenic compounds that directly interact with DNA or when the carcinogenic mechanism is unknown. Because the mode of action of arsenic-induced carcinogenesis is not well established, recent dose-response assessments for arsenic have assumed linearity at low doses despite evidence that arsenic is not a direct-acting mutagen. Several modes of action, including generation of oxidative stress, perturbation of DNA methylation patterns, inhibition of DNA repair, and modulation of signal transduction pathways, have been proposed to characterize arsenic's toxicity. It is probable that these mechanisms do not act in isolation, but overlap, and contribute to the complex nature of arsenic-induced carcinogenesis. All of the proposed mechanisms are likely to be nonlinear at low does. Furthermore, studies of populations outside the US exposed to arsenic in drinking water show increases in cancer only at relatively high concentrations, that is, concentrations in drinking water of several hundred micrograms per liter (microg/l). Studies in the US of populations exposed to average concentrations in drinking water up to about 190 microg/l do not provide evidence of increased cancer. Consideration of arsenic's plausible mechanisms and evidence from epidemiological studies support the use of nonlinear methods, either via biologically based modeling or use of a margin-of-exposure analysis, to characterize arsenic risks.

Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial.

CONTEXT: Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective. OBJECTIVE: To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics. PATIENTS: A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy. INTERVENTION: After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks. MAIN OUTCOME MEASURES: Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity). RESULTS: Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P =.007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P =.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group. CONCLUSION: Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.