The use of parent-completed questionnaires to investigate developmental outcomes in large populations of children exposed to antiseizure medications in pregnancy.

OBJECTIVE: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives. METHODS: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases. RESULTS: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%). SIGNIFICANCE: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3.

Neurodevelopment of babies born to mothers with epilepsy: A prospective observational cohort study.

OBJECTIVE: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow-up. METHODS: Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition). RESULTS: There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (-.74, SE = 2.9, 95% confidence interval [CI] = -6.5 to 5.0, p = .80) or levetiracetam (-1.57, SE = 3.1, 95% CI = -4.6 to 7.7, p = .62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low. SIGNIFICANCE: These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow-up is required to rule out later emerging effects.

Antiepileptic Drug Teratogenicity and De Novo Genetic Variation Load.

OBJECTIVE: The mechanisms by which antiepileptic drugs (AEDs) cause birth defects (BDs) are unknown. Data suggest that AED-induced BDs may result from a genome-wide increase of de novo variants in the embryo, a mechanism that we investigated. METHODS: Whole exome sequencing data from child-parent trios were interrogated for de novo single-nucleotide variants/indels (dnSNVs/indels) and de novo copy number variants (dnCNVs). Generalized linear models were applied to assess de novo variant burdens in children exposed prenatally to AEDs (AED-exposed children) versus children without BDs not exposed prenatally to AEDs (AED-unexposed unaffected children), and AED-exposed children with BDs versus those without BDs, adjusting for confounders. Fisher exact test was used to compare categorical data. RESULTS: Sixty-seven child-parent trios were included: 10 with AED-exposed children with BDs, 46 with AED-exposed unaffected children, and 11 with AED-unexposed unaffected children. The dnSNV/indel burden did not differ between AED-exposed children and AED-unexposed unaffected children (median dnSNV/indel number/child [range] = 3 [0-7] vs 3 [1-5], p = 0.50). Among AED-exposed children, there were no significant differences between those with BDs and those unaffected. Likely deleterious dnSNVs/indels were detected in 9 of 67 (13%) children, none of whom had BDs. The proportion of cases harboring likely deleterious dnSNVs/indels did not differ significantly between AED-unexposed and AED-exposed children. The dnCNV burden was not associated with AED exposure or birth outcome. INTERPRETATION: Our study indicates that prenatal AED exposure does not increase the burden of de novo variants, and that this mechanism is not a major contributor to AED-induced BDs. These results can be incorporated in routine patient counseling. ANN NEUROL 2020;87:897-906.

Non-toxic total nitrogen determination using a low alkaline persulfate digestion.

Measuring total nitrogen, nitrate, and nitrite is critical for compliance with water safety standards. Previous methods for measuring total nitrogen were hazardous, time consuming, and expensive. Here we report a method for measuring total nitrogen in water and soil using alkaline persulfate digestion combined with a Nitrate Reductase assay. In this method the alkaline persulfate reaction oxidizes all nitrogen present in the sample to nitrate, Nitrate Reductase then is used to catalyze the reduction of nitrate to nitrite in the presence of NADH. The nitrite is then treated with Griess reagents to produce a pink color. The absorbance of this color is measured at 540 nm using a spectrophotometer and when compared to a standard curve of nitrate, treated with both the reduction and colorizing steps, can be used to determine the total nitrogen content of measured samples. This method customizes the measurement of total nitrogen by combining alkaline persulfate digestion with a Nitrate Reductase assay using enzyme based green chemistry. •Customization of total nitrogen analysis by combining alkaline persulfate digestion, driving all nitrogen to nitrate, with a colorimetric nitrate reductase assay•Nitrate reductase catalyzes all nitrate, produced by alkaline persulfate digestion and present in the original sample, to nitrite•Nitrite is measured by the addition of sulfanilamide and N-(1-napthyl)ethylenediamine dihydrochloride, resulting in a pink color.

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy.

OBJECTIVE: To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME). METHODS: People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12-month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females. RESULTS: We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08-1.13], P < 0.001) and female sex (1.41 [1.07-1.85], P = 0.02) were associated with shorter trial duration. Valproate was associated with the longest treatment duration; trials with carbamazepine and topiramate were significantly shorter (HR [CI]: 3.29 [2.15-5.02], P < 0.001 and 1.93 [1.31-2.86], P < 0.001). The relative frequency of valproate trials shows a decreasing trend since 2003 while there is an increasing trend for levetiracetam. Fewer females than males received valproate (76.2% vs 92.6%, P = 0.001). SIGNIFICANCE: In people with JME, valproate is an effective AED; levetiracetam emerged as an alternative. Valproate is now contraindicated in women of childbearing potential without special precautions. With appropriate selection and safeguards in place, valproate should remain available as a therapy, including as an alternative for women of childbearing potential whose seizures are resistant to other treatments.

Comparative effectiveness of radiotherapy for early-stage hormone receptor-positive breast cancer in elderly women using real-world data.

BACKGROUND: Radiotherapy is the recommended treatment after breast-conserving surgery (BCS) for early-stage breast cancer (BC). However, there is no clear evidence whether radiotherapy after BCS improves the survival of elderly women diagnosed with early-stage hormone receptor-positive (HR+) BC. The aim of this study was to investigate the survival benefit associated with radiotherapy plus hormonal therapy vs hormonal therapy alone after BCS for early-stage HR+ BC patients. METHODS: Using the Surveillance, Epidemiology, and End Results linked with Medicare data, we identified elderly (65 years and older) women diagnosed with early-stage HR+ BC (2006-2011) who received hormonal therapy with or without radiotherapy after BCS. A log-rank test, Cox proportional hazards models, and propensity score matching were used to estimate the overall survival (OS) benefit associated with radiotherapy after BCS. RESULTS: Of the 5688 patients, there were 303 deaths from any cause. One hundred and eighty-five (61%) of these deaths occurred in the hormonal therapy group, and 118 (39%) deaths occurred in the radiotherapy plus hormonal therapy group. The mean survival time in the radiotherapy plus hormonal therapy group was 5.32 ± 1.86 years compared with 4.92 ± 1.86 years in the hormonal therapy group. Based on the adjusted and propensity score matching analysis, patients in the adjuvant radiotherapy group had a lower risk of death compared with those who did not receive radiotherapy. Radiotherapy plus hormonal therapy decreased the risk of death by 32%. The effect estimates were similar in the adjusted and matched cohorts. CONCLUSIONS: Radiotherapy plus hormonal therapy resulted in a significant improvement in the OS of elderly women diagnosed with HR+ BC.

Assessing the Level of Patient-Specific Treatment Recommendations in Clinical Practice Guidelines for Hemodialysis Vascular Access in the United States.

BACKGROUND: Hemodialysis is a procedure that requires efficient removal and return of blood to a patient's body. Despite being a life-sustaining process, hemodialysis is associated with morbidity, mortality, and high societal costs. A significant part of the financial costs to patients and society at large can be attributed to vascular access dysfunction. The cornerstone to efficient hemodialysis is a well-functioning vascular access that simultaneously allows efficient blood flow for dialysis and easy cannulation. It is hypothesized that the poor health outcomes associated with vascular access dysfunction can be improved by paying closer attention to patient-specific factors in clinical guidelines for hemodialysis vascular access. This may require a shift to a more patient-centered approach to vascular access management. OBJECTIVE: To assess the presence of patient-specific treatment recommendations in the current clinical practice guidelines for hemodialysis vascular access. METHODS: We conducted a systematic search of PubMed and professional nephrology organization websites for full-text clinical practice guidelines with treatment recommendations regarding hemodialysis vascular access. We developed a coding sheet to document the number of patient-specific treatment recommendations and other quality attributes found in the extracted clinical practice guidelines. RESULTS: Our search resulted in the extraction of 5 clinical practice guidelines for final review. Only 1 of the 5 extracted guidelines was found to contain patient-specific treatment recommendations, but the treatment recommendations were limited to juvenile patients. Of the 5 clinical practice guidelines, 4 were published within the past decade (ie, after 2006). CONCLUSION: Our findings show that current clinical practice guidelines for hemodialysis vascular access lack patient-specific recommendations. Future clinical guidelines must consider patient-specific treatment recommendations with the goal of improving hemodialysis vascular access outcomes for patients, a goal that is supported in the recommendations of the National Kidney Foundation.

Comparing Treatment Modalities for End-Stage Renal Disease: A Meta-Analysis.

BACKGROUND: End-stage renal disease (ESRD) imposes significant economic and social burdens on patients and healthcare systems. In the United States alone, more than 600,000 Americans have ESRD, with an estimated annual cost of treatment of more than $30 billion. Peritoneal dialysis and hemodialysis are competing renal replacement therapies in ESRD; however, data comparing quality-of-life outcomes between these 2 modalities are limited. OBJECTIVES: To compare the effectiveness of peritoneal dialysis with the more common treatment modality of hemodialysis on the health-related quality of life (HRQoL) of patients with ESRD in the general, physical, and psychological domains; and to determine whether the time of publication and the origin of each study influenced its findings regarding the effectiveness of the 2 modalities. METHODS: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to collect the data. PubMed, MEDLINE, and PsycINFO were the primary databases searched. Only articles published in English were included in this meta-analysis. The measure of effect size was Cohen's standardized mean difference. A random-effects model was used to test the hypothesis of equality in the mean HRQoL. RESULTS: A total of 15 studies with a combined sample size of 4318 patients met the study criteria and were included in the analysis. The pooled effect sizes based on the random-effects model were 0.24 (95% confidence interval [CI], -0.17-0.66) in the general domain; 0.10 (95% CI, -0.09-0.29) in the physical-functioning domain; and 0.29 (95% CI, -0.13-0.71) in the psychological-functioning domain. None of the summary effect sizes was statistically significant. Subgroup analyses favored peritoneal dialysis regarding the time and country of publication. CONCLUSION: The majority of the studies included in this analysis favored peritoneal dialysis over hemodialysis in all 3 domains. However, the pooled effect sizes were not significant, resulting in the inability to conclude that peritoneal dialysis is the more effective of these 2 treatment modalities.

Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations.

OBJECTIVES: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. METHODS: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. RESULTS: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). CONCLUSION: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes.

Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. METHODS: Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. RESULTS: Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. SIGNIFICANCE: Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS.

The Relation among Prostate Cancer Knowledge and Psychosocial Factors for Prostate Cancer Screening among African American Men: a Correlational Study.

African American (AA) men face disproportionately higher rates of prostate cancer (PCa) in comparison to other races. In addition, higher mortality rates from PCa amongst AA men signifies PCa as a formidable health disparity. Inconsistent PCa screening guidelines among medical organizations, further clouds one's decision on receiving a PCa screening. Examining various relations among factors which influence PCa screening may provide insight into their decision whether or not to receive a PCa screening. The purpose of the study was to examine the presence of associations among PCa knowledge, psychosocial factors, and PCa screening over a six month time frame. There were 76 participants at baseline, intervention group (n = 37) and control group (n = 35) and 54 participants, intervention group (n = 26) and control group (n = 28) remained at the 6 month follow up. At the six month follow up, the control group was more likely to have not received a PCa screening and the intervention group was more likely to have received a PCa screening, p < 0.01. PCa knowledge scores rose from 49% to 71%, intervention group, and 52% to 58%, control group. Significant associations were found among the following covariates, age and religion (rs = 0.499, p < 0.01), income and education (rs = 0.535, p < 0.01), income and healthcare coverage (rs = 0.528, p < 0.01), income and PCa knowledge at 6 months (rs = 0.424, p < 0.01), PCa screening and religion (rs = 0.353, p < 0.01), healthcare empowerment and preparation for decision making (rs = 0.421, p < 0.01), decisional self-efficacy and active surveillance knowledge (rs = 0.377, p < 0.01), and active surveillance knowledge and PCa knowledge (rs = 0.497, p < 0.01). The study revealed associations among PCa knowledge and psychosocial factors regarding a decision for PCa screening among the PCa high risk group, AA men.

Comparison of health utility weights among elderly patients receiving breast-conserving surgery plus hormonal therapy with or without radiotherapy.

BACKGROUND: The selection of the most appropriate treatment combinations requires the balancing of benefits and harms of these treatment options as well as the patients' preferences for the resulting outcomes. OBJECTIVE: This research aimed at estimating and comparing the utility weights between elderly women with early stage hormone receptor positive (HR+) breast cancer receiving a combination of radiotherapy and hormonal therapy after breast conserving surgery (BCS) and those receiving a combination of BCS and hormonal therapy. METHODS: The Surveillance, Epidemiology, and End Results (SEER) linked with Medicare Health Outcomes Survey (MHOS) was used as the data source. Health utility weights were derived from the VR-12 health-related quality of life instrument using a mapping algorithm. Descriptive statistics of the sample were provided. Two sample t-tests were performed to determine potential differences in mean health utility weights between the two groups after propensity score matching. RESULTS: The average age at diagnosis was 72 vs. 76 years for the treated and the untreated groups, respectively. The results showed an inverse relationship between the receipt of radiotherapy and age. Patients who received radiotherapy had, on average, a higher health utility weight (0.70; SD = 0.123) compared with those who did not receive radiotherapy (0.676; SD = 0.130). Only treated patients who had more than two comorbid conditions had significantly higher health utility weights compared with patients who were not treated. CONCLUSIONS: The mean health utility weights estimated for the radiotherapy and no radiotherapy groups can be used to inform a comparative cost-effectiveness analysis of the treatment options. However, the results of this study may not be generalizable to those who are outside a managed care plan because MHOS data is collected on managed care beneficiaries.

Utilizing Genomics through Family Health History with the Theory of Planned Behavior: Prediction of Type 2 Diabetes Risk Factors and Preventive Behavior in an African American Population in Florida.

AIM: African Americans are disproportionately affected by type 2 diabetes. The purpose of this study was to assess to what extent African Americans' knowledge and awareness of family health history and related risk factors for developing type 2 diabetes influence their likelihood of adopting a preventive behavior. METHODS: This study employed an anonymous pencil-and-paper, self-administered survey consisting of two sections. Section 1 was a modified version of the US Surgeon General's Family Health History Initiative and the American Diabetes Association Diabetes Risk Factor Survey. Section 2 of the survey was based on the constructs of the theory of planned behavior. Over 394 African American participants completed the survey. RESULTS: 'Perceived behavioral control' was the strongest predictor of 'likelihood of adopting preventive behavior'. Participants were aware of their family history as a risk factor for type 2 diabetes, but it was not a significant predictor of behavior modifications based on that knowledge. CONCLUSION: The lack of perceived risk in this population shows the importance of not only knowing one's risk factors but translating those risk factors to a more personalized form that fits into the current lifestyle of the individual in a meaningful way.

Determination of phosphate in soil extracts in the field: A green chemistry enzymatic method.

Measurement of ortho-phosphate in soil extracts usually involves sending dried samples of soil to a laboratory for analysis and waiting several weeks for the results. Phosphate determination methods often involve use of strong acids, heavy metals, and organic dyes. To overcome limitations of this approach, we have developed a phosphate determination method which can be carried out in the field to obtain results on the spot. This new method uses: •Small volumes.•An enzymatic reaction.•Green chemistry. First, the soil sample is extracted with deionized water and filtered. Next, an aliquot of the soil extract (0.5 mL) is transferred to a disposable cuvette, containing 0.5 mL of reaction mixture [200 mM HEPES, pH 7.6, 20 mM MgCl2, with 80 nmol 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG) and 1 unit of recombinant purine nucleoside phosphorylase (PNP; EC 2.4.2.1)], mixed, and incubated for 10 min at field temperature. Absorbance of the completed reaction is measured at 360 nm in open-source, portable photometer linked by bluetooth to a smartphone. The phosphate and phosphorus content of the soil is determined by comparison of its absorbance at 360 nm to a previously prepared standard phosphate curve, which is stored in the smartphone app.

Developmental changes in the connective tissues of the porcine recurrent laryngeal nerve.

The recurrent laryngeal nerve (RLN) branches from the vagus cranial nerve to innervate structures important for voicing and swallowing. Damage to this nerve, commonly associated with surgery or idiopathic etiologies that largely occur with aging, results in impaired voicing and swallowing (Myssiorek, 2004). Sunderland proposed a model of peripheral nerve damage whereby a nerve's ability to resist damage from stretch and compression is determined by the quantity and composition of its epineurial connective tissues (Sunderland, 1951). Thus, it would be expected that epineurium differs depending upon the forces imposed on a nerve within its anatomical setting. The purpose of this study was to investigate RLN epineurium quantity and composition with development. A porcine model (piglet vs. juvenile) was used because of the similarity between porcine and human laryngeal innervation, anatomy and function. The entire RLN was excised bilaterally, and stereological methods were used to quantify the composition of epineurial connective tissues. Compared with the piglet, the juvenile pig RLN was double the diameter. While the piglet had no differences in the percentage of epineurial collagen and adipose between proximal and distal segments of both sides of the RLN, the juvenile pig had a greater percentage of collagen in the proximal segment of both sides of the RLN and a greater percentage of adipose in the distal segment of the left RLN compared with the proximal segment. In addition, unlike the piglet, the juvenile pig had a greater number of fascicles in the proximal than distal segment of the RLN, regardless of nerve side. These findings are consistent with predicted patterns associated with the different anatomical settings of the left and right RLN, show that the RLN changes with age, and support Sunderland's model.

Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero.

PURPOSE: Use of antiepileptic drugs in pregnancy is associated with congenital malformations and developmental delay. Previous studies have suggested that women who have had one child with a congenital malformation are at increased risk of having other children with malformations. We sought to confirm the magnitude of risk in a large cohort drawn from the United Kingdom Epilepsy and Pregnancy Register. METHODS: The United Kingdom Epilepsy and Pregnancy Register is a prospective, observational registration and follow-up study set up to determine the relative safety of antiepileptic drugs in pregnancy. We have extracted data for those women who prospectively registered more than one pregnancy and calculated the recurrence risks for fetal malformations. KEY FINDINGS: Outcome data were available for 1,534 pregnancies born to 719 mothers. For women whose first child had a congenital malformation there was a 16.8% risk of having another child with a congenital malformation, compared with 9.8% for women whose first child did not have a malformation (relative risk 1.73, 95% confidence interval [CI] 1.01-2.96). The risk for recurrence was 50% for women who had had two previous children with a congenital malformation. There was a trend toward a higher risk for recurrent malformations in pregnancies exposed to valproate (21.9%, relative risk 1.47, 95% CI 0.68-3.20) and topiramate (50%, relative risk 4.50, 95% CI 0.97-20.82), but not for other drugs such as carbamazepine and lamotrigine. Recurrence risks were also higher for pregnancies exposed to polytherapy regimens and for those where the dose of antiepileptic drug treatment had been increased after the first pregnancy. SIGNIFICANCE: Women who have had a child with a malformation are at increased risk of having other children with malformations. This is in keeping with previous reports that have suggested that genetic influences may be one of the factors determining the teratogenic risk of antiepileptic drugs.

Cardiorenal medicine: partners in practice?

Cardiorenal medicine is an exciting and evolving area of medicine. There is still much to learn about the complex pathophysiological process of the cardiorenal syndrome. The latest ideas and research were discussed at the 5th Annual Cardiorenal Forum on 15th October 2010.

Regional variations in cancer screening rates found in women with diabetes.

BACKGROUND: A review of the literature gives conflicting findings regarding gender-specific cancer screening rates found in women with chronic illness. OBJECTIVES: The purpose of this study was to determine if women with diabetes have different patterns of cancer screening than women of the general population, and if so, to identify the determinants of these screening patterns guided by the Predisposing, Reinforcing, and Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE) model. METHODS: The 12 states using the optional women's health module for the 2003 Behavioral Risk Factor Surveillance System were downloaded into the STATA software. Contingency tables were used to identify the prevalence of cancer screening in women who self-report that they have diabetes in comparison with women who report being nondiabetic. Logistic regression was used to examine the association between the PRECEDE model determinants and the screening behaviors. RESULTS: No significant association was found between having a diagnosis of diabetes and having mammography screening rates (F = 1.5, p =.22). However, cervical cancer screening rates were statistically significantly different between the two groups of women (F = 39.01, p <.01). A gap in cervical cancer screening rates was identified among women with diabetes as compared with women without diabetes (78% versus 86%, respectively). Regional exceptions were noted between the 12 states. Ten of the 11 PRECEDE variables demonstrated a significant association with Papanicolaou test screening rates. The states demonstrating inadequate screening rates were the states with the most negative PRECEDE factors. DISCUSSION: Research has shown that the primary reason women seek cancer screening is when they are encouraged by a healthcare provider. If other care providers are focused on disease management, nurses who provide holistic care can build on the advocacy role inherent in nursing and encourage screening in underserved areas of the country.

Personal factors affecting African-American men's prostate cancer screening behavior.

PURPOSE: Although there are significant controversies about prostate cancer screening, it is the only method recognized to combat prostate cancer through early detection and appropriate treatment. The primary goal of this study was to identify personal factors influencing African-American men's participation in prostate cancer screening. METHODS: Two cross-sectional mail surveys were conducted over one year to test the validity of the Attitude-Social Influence-Efficacy model in predicting prostate cancer screening. Data were collected from African-American men age > or =40. The study hypotheses were tested using multiple linear regression and logistic regression analyses RESULTS: One-hundred-ninety-one African-American men participated in the first cross-sectional survey, and 65 African-American men responded to the follow-up survey a year later. The participants were mostly African-American men who were born and grew up in America, were 50-59 years of age, had some college training, were married, were urban residents, had full-time employment status and had a household income of $20,000-$39,000. The key determinants of intention to undergo prostate cancer screening were attitude, perceived behavioral control, past behavior and perceived susceptibility. Attitude was the primary determinant of screening behavior. CONCLUSION: To foster appropriate prostate cancer detection activities, the modifiable factors identified in this study should be considered.