Exposure to Macrolides During Pregnancy and the Risk for Spontaneous Abortions: A Population-Based Retrospective Cohort Study.

Previous studies evaluating the risk of spontaneous abortions following exposure to macrolides reported controversial results. The goal of the current study was to examine the risk for spontaneous abortions following exposure to macrolides during pregnancy. We conducted a population-based retrospective cohort study by linking three computerized databases: Clalit Health Services drug dispensation database, Soroka Medical Center (SMC) birth database, and SMC hospitalizations database. Multivariate time-varying Cox regressions were performed and adjusted for suspected confounders and known risk factors for spontaneous abortions. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. A secondary analysis was performed to assess the association between exposure to macrolides in terms of the defined daily dose dispensed and spontaneous abortions. The study cohort included 65,457 pregnancies that ended at Soroka Medical Center between 2004 and 2009, of which 6508 (9.9%) resulted in a spontaneous abortion. A total of 825 (1.26%) pregnancies were exposed to macrolides during the exposure period. Exposure to macrolides was not associated with spontaneous abortions as a group (adjusted HR 1.00 95% CI 0.77-1.31) or as specific medications. There was no evidence of a dose-response relationship between exposure to macrolides and spontaneous abortions. In conclusion, this population-based retrospective cohort study did not detect an increased risk for spontaneous abortion following exposure to macrolides during the first trimester of pregnancy.

Therapeutic drug monitoring of lacosamide among children: is it helpful?

Objective: This study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with epilepsy using LCM serum concentration and its correlation to the age of the participants and the dosage of the drug. Methods: Demographic and clinical data were collected from the medical records of children with epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered weight-based medication dosing and clinical report. Results: Forty-two children aged 10.43 ± 5.13 years (range: 1-18) were included in the study. The average daily dose of LCM was 306.62 ± 133.20 mg (range: 100-600). The average number of seizures per day was 3.53 ± 7.25 compared to 0.87 ± 1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74 ± 3.27 mg/L. No statistically significant association was found between LCM serum levels and the clinical response (p = 0.58), as well as the correlation between LCM dosage and the change in seizure rate (p = 0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n = 17) females (n = 23) (p = 0.31 and p = 0.94, respectively). A positive trend was found between age and LCM serum concentrations (r = 0.26, p = 0.09). Conclusion: Based on the data that has been obtained from our study, it appears that therapeutic drug monitoring for LCM may not be necessary. Nonetheless, further research in this area is needed in the light of the relatively small sample size of the study.

Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Patient safety culture as a space of social struggle: understanding infection prevention practice and patient safety culture within hospital isolation settings - a qualitative study.

BACKGROUND: In recent times, infection prevention and patient safety have become a global health policy priority with thought being given to understanding organisational culture within healthcare, and of its significance in initiating sustained quality improvement within infection prevention and patient safety. This paper seeks to explore the ways in which engagement of healthcare workers with infection prevention principles and practices, shape and inform patient safety culture within the context of hospital isolation settings; and vice-versa. RESEARCH METHODS: In this paper, we utilise focus group interviews at two hospital sites within one health board in order to engage healthcare staff in elaborating on their understandings of infection prevention practices and patient safety culture within isolation settings in their organisation. Focus group transcripts were analysed inductively using thematic analysis in order to identify and develop emerging empirical themes. RESULTS: Positioned against a background of healthcare restructuring and ever-increasing uncertainty, our study found two very different hospitals in regard to patient safety culture and infection prevention practice. While one hospital site embodies a mixed picture in regard to patient safety culture, the second hospital is best characterised as being highly fragmented. The utilisation of focus group interviews revealed themes that capture the ways in which interviewees position and understand the work they perform within the broader structural, political and cultural context, and what that means for infection prevention practice and patient safety culture. CONCLUSION: Drawing on the insights of Bourdieu, this paper theorises the field of patient safety as a space of social struggle. Patient safety is thus positioned within its structural, cultural and political context, rather than as merely an epidemiological dilemma.

Bone mineral density alteration in obstructive sleep apnea by derived computed tomography screening.

The association between obstructive sleep apnea (OSA) and bone mineral density (BMD) is poorly elucidated and has contradictory findings. Abdominal computed tomography (CT) for other indications can provide a valuable opportunity for osteoporosis screening. Thus, we retrospectively explored the association between OSA and BMD by examining abdominal CT vertebrae images for a multitude of conditions and indications. We included 315 subjects (174 with OSA and 141 without OSA) who performed at least two CT scans (under similar settings). Both groups had a similar duration between the first and second CT scans of 3.6 years. BMD decreased in those with OSA and increased age. A multivariate linear regression indicated that OSA is associated with BMD alterations after controlling for age, gender, and cardiovascular diseases. Here, we report that OSA is associated with BMD alterations. Further studies are required to untangle the complex affect of OSA on BMD and the possible clinical implications of vertebra-depressed or femoral neck fractures.

Comparison of Conditional and Marginal Models in Assessing a Child Nutrition Intervention in Armenia.

INTRODUCTION: Child malnutrition is a major issue in conflict zones. Evidence-based interventions and their thorough evaluation could help to eliminate malnutrition. We aimed to assess the causal effect of a community-based multidisciplinary nutrition program for children in a chronic conflict zone near the northeastern border of Armenia on two main outcomes: stunting and anemia. We further compared the interpretations and public health relevance of the obtained effect estimates. METHODS: In 2016, the study measured hemoglobin and anthropometric measures and collected data from the children's caregivers. We used propensity score matching analyses, inverse probability weighting, and overlap weighting methods to examine the average treatment effects among treated population (ATT), and among population with overlapping weights (ATO). RESULTS: The ATT for stunting among children who participated in the intervention program estimated by propensity score matching analyses (PSM-ATT) was (1.95; 95%CI 1.15-3.28). Nevertheless, children who took part in the program had a lower risk of anemia (0.28; 95%CI 0.19-0.42). The ATT, estimated by inverse probability weighting (IPTW-ATT), was slightly lower for stunting (1.82; 95%CI 1.16-2.86) while similar for anemia (0.33; 95%CI 0.23-0.46) compared to PSM-ATT. Compared to the IPTW-ATT and PSM-ATT the ATO was lower for stunting (1.75; 95%CI 1.14-2.68) and similar for anemia (0.31; 95%CI 0.22-0.43). DISCUSSION: Marginal models could be used in similar quasi-experimental settings to identify the causal effect of interventions in specific populations of interest. Nonetheless, these methods do not eliminate threats to internal validity. Thorough study design and accurate data collection are necessary to improve the efficiency of marginal models.

Modified bi-weekly cetuximab-cisplatin and 5-FU/leucovorin based regimen for effective treatment of recurrent/metastatic head and neck squamous cell carcinoma to reduce chemotherapy exposure of patients.

BACKGROUND: The standard chemotherapy treatment protocol for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) requires as long as 56 days of hospitalization over six months. Where the 5-Fluorouracil (5-FU) pump is available, most treatment will be on outpatient bases, however patients will still be under chemotherapy treatment for a comparable period of time (around 50 days). AIM: A modified protocol was assessed to decrease hospitalization and/or chemotherapy treatment time without sacrificing outcomes, to potentially increase patient quality of life. METHODS AND RESULTS: A retrospective analysis (2005-2018) of recurrent/metastatic HNSCC patients with a modified treatment protocol was performed. Treatment consisted of cisplatin, cetuximab, 5-fluorouracil bolus and leucovorin administered on day 1 of a 2-week cycle, and a continuous infusion of 5-fluorouracil on days 1-2 of the cycle. Outcomes were measured by progression-free survival, overall survival, and patient hospitalization time. Analysis was done using the Kaplan-Meier survival function curve. The study cohort consisted of 27 patients. The modified treatment protocol resulted in a median progression-free survival of nine months and median overall survival of 14 months, while hospitalization time was reduced by almost 80% in the first six months of treatment. CONCLUSIONS: Modification of the cisplatin, cetuximab, 5-FU and leucovorin protocol to a bi-weekly regimen utilizing alternative drug delivery methods, significantly reduced patient hospitalization from 56 days to 12 days in the first 6 months of treatment. This was achieved without compromising treatment outcome, while significantly reducing the days patients were exposed to chemotherapy, and thus potentially improving quality of life.

Obstructive sleep apnea and metabolic disorders in morbidly obese adolescents.

BACKGROUND: Little known about the prevalence of obstructive sleep apnea (OSA) in morbid obese adolescents and the association between OSA and comorbid factors. AIM: To examine the association between apnea-hypopnea index (AHI, a measure for OSA severity) and metabolic morbidity among morbidly obese adolescents. METHODS: We performed a population-based retrospective cohort study by reviewing sleep study, metabolic indices, and comorbidity-related data of a cohort (n = 106) of adolescents referred to a bariatric surgery clinic. We compared subjects with moderate/severe OSA (AHI ≥ 5) versus no/mild OSA (AHI < 5) OSA and three groups of subjects with increasing body mass index (BMI) concerning sleep-study and metabolic indices using univariate analyses. To assess the link between AHI and ferritin levels a multivariate linear regression (adjusted for BMI and mean cell volume) was preformed. RESULTS: A total of 71 patients met the inclusion criteria. Subjects with moderate/severe OSA (n = 32, 45%) had higher BMI, cholesterol, cholesterol/high-density lipoprotein (HDL) ratio, hemoglobin A1c, and serum ferritin levels (p < .05). AHI significantly increased across BMI strata (p = .02). Multivariate linear regression indicated that moderate/severe OSA was associated with higher levels of ferritin, unstandardized ß = 49.1 (nIU/ml) (p = .025). CONCLUSIONS: Morbidly obese adolescents with moderate/severe OSA versus no/mild OSA have a higher risk for metabolic complications. Therefore, OSA management should be considered in adolescents with morbid obesity, in addition to weight loss.

Prenatal exposure to organophosphate and pyrethroid insecticides and the herbicide 2,4-dichlorophenoxyacetic acid and size at birth in urban pregnant women.

BACKGROUND: Organophosphate insecticides and the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) are used to protect crops or control weeds. Pyrethroids are used to manage pests both in agriculture and in residences, and to reduce the transmission of insect-borne diseases. Several studies have reported inverse associations between exposure to organophosphates (as a larger class) and birth outcomes but these associations have not been conclusive for pyrethroids or 2,4-D, specifically. We aimed to investigate the association between birth outcomes and urinary biomarkers of pyrethroids, organophosphates and 2,4-D among healthy pregnant women living in New York City. METHODS: We quantified urinary biomarkers of 2,4-D and of organophosphate and pyrethroid insecticides from 269 women from two cohorts: a) Thyroid Disruption And Infant Development (TDID) and b) Sibling/Hermanos cohort (S/H). We used weighted quantile sum regression and multivariable linear regression models to evaluate the associations between a mixture of urinary creatinine-adjusted biomarker concentrations and birth outcomes of length, birthweight and head circumference, controlling for covariates. We also used linear regression models and further classified biomarkers concentrations into three categories (i: non-detectable; ii: between the limit of detection and median; and iii: above the median) to investigate single pesticides' association with these birth outcomes. Covariates considered were delivery mode, ethnicity, marital status, education, income, employment status, gestational age, maternal age and pre-pregnancy BMI. Analyses were conducted separately for each cohort and stratified by child sex within each cohort. RESULTS: In TDID cohort, we found a significant inverse association between weighted quantile sum of mixture of pesticides and head circumference among boys. We found that the urinary biomarkers of organophosphate chlorpyrifos, TCPy, and 2,4-D had the largest contribution to the overall mixture effect in the TDID cohort among boys (b = -0.57, 95%CI: -0.92, -0.22) (weights = 0.81 and 0.16 respectively) but not among girls. In the multivariable linear regression models, we found that among boys, for each log unit increase in 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of organophosphate chlorpyrifos) in maternal urine, there was a -0.56 cm decrease in head circumference (95%CI: -0.92, -0.19). Among boys in the TDID cohort, 2,4-D was associated with smaller head circumference in the second (b = -1.57; 95%CI: -2.74, -0.39) and third (b = -1.74, 95%CI: -2.98, -0.49) concentration categories compared to the first. No associations between pyrethroid and organophosphate biomarkers and birth outcomes were observed in girls analyzed in WQS regression or individually in linear regression models in TDID cohort. In the S/H cohort, head circumference increased with higher concentrations of 3-phenoxybenzoic acid (3-PBA, a biomarker of several pyrethroids) (b = 0.53, 95%CI: 0.03, 1.04) among boys and head circumference was lower among girls in the high compared to low category of 2,4-D (b = -2.27, 95%CI: - 3.98, -0.56). Birth length was also positively associated with the highest concentration of 2,4-D compared to the lowest among boys (b = 4.01, 95%CI: 0.02,8.00). CONCLUSIONS: Weighted quantile sum of pesticides was negatively associated with head circumference among boys in one cohort. Nonetheless, due to directional homogeneity assumption in WQS no positive associations were detected. In linear regression models with individual pesticides, concentrations of TCPy were inversely associated with head circumference in boys and higher concentrations of 2,4-D was inversely associated with head circumference among girls; 2,4-D concentrations were also associated with higher birth length among boys. Concentrations of 3-PBA was positively associated with head circumference among boys.

Risk for preeclampsia following exposure to PM2.5 during pregnancy.

BACKGROUND: Previous findings concerning the risk for preeclampsia following exposure to particulate matter are inconclusive. METHODS: We used data from all singleton pregnancies of women insured by the "Clalit health services" (CHS) maintenance organization in southern Israel that resulted in delivery or perinatal mortality at Soroka Medical Center (SMC). Daily PM2.5 concentrations were estimated by a hybrid satellite-based model at one-squared kilometer spatial resolution. We used Cox proportional hazard models coupled with distributed lag models to examine the association between the mean exposure to PM2.5 in every gestational week and the diagnosis of preeclampsia, adjusting for maternal age, parity, year of birth, season of birth and socio-economic status. Hazard Ratios (HR) and 95% Confidence Intervals (CI) were calculated for individual gestational weeks and for cumulative exposure until the 25th gestational week. RESULTS: A total of 133,197 pregnancies ended at SMC during the study period, of which 68,126 (51.1%) were Jewish and 65,071 (48.9%) were Bedouin. For pregnancies of Jewish women, exposure to PM2.5 from the 7th until the 14st gestational week was significantly associated with preeclampsia (maximal HR = 1.06; 95%CI: 1.01 - 1.11 during the 10th gestational week per 10 µg/m3 increase in PM2.5). Cumulative exposure to PM2.5 during the first 25th gestational weeks was also significantly associated with preeclampsia (HR = 2.08; 95%CI: 1.10 - 3.94 per 10 µg/m3 increase in PM2.5). We observed no association for pregnancies of Bedouin women. CONCLUSIONS: Exposure to PM2.5 between the 7th and the 14st gestational weeks was associated with preeclampsia among Jewish women but not among Bedouin women.

Hepatic and cardiac iron load as determined by MRI T2* in patients with congenital dyserythropoietic anemia type I.

Iron overload comprises one of the main complications of congenital dyserythropoietic anemia type I (CDA-I). When analyzing magnetic resonance imaging T2* (MRI T2*) results in CDA patients, two previous studies reported discordant results regarding iron load in these patients. To further understand iron loading pattern in this group of patients, we analyzed MRI T2* findings in 46 CDA-I patients. Mild to moderate hepatic iron overload was detected in 28/46 (60.8%) patients. A significant correlation was found between serum ferritin and liver iron concentration (LIC). A significant correlation (p value = 0.02) was also found between the patient's age and LIC, reflecting increased iron loading over time, even in the absence of transfusion therapy. Notably, no cardiac iron overload was detected in any patient. Transfusion-naive patients had better LIC and better cardiac T2* values. These results demonstrate that a high percentage of CDA-I patients have liver iron concentration above the normal values, risking them with significant morbidity and mortality, and emphasize the importance of periodic MRI T2* studies for direct assessment of tissue iron concentration in these patients, taking age and transfusional burden into consideration.

Prenatal and early childhood exposure to phthalates and childhood behavior at age 7 years.

BACKGROUND: Emerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific. METHODS: In a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately. RESULTS: Among boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations. CONCLUSION: Concentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific.

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance.

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus. This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns. Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables. Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns. This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

Perinatal phthalates exposure decreases fine-motor functions in 11-year-old girls: Results from weighted Quantile sum regression.

INTRODUCTION: Phthalates are a group of high production chemicals, generally used as plasticizers and odor enhancers. Phthalates cross the blood-placenta barrier and are associated with deficits in cognitive functions and behavior problems in offspring. We previously reported sex-specific associations with motor function when phthalates are considered singly. Because exposure to phthalates usually occurs as mixtures, here we assess these associations between a mixture of phthalates and motor function at age 11 years. METHODS: Data come from the prospective cohort study of mothers and offspring who participated in the Columbia Center for Children's Environmental Health birth cohort (CCCEH). Seven phthalate metabolites were measured in maternal spot urine obtained during the third trimester and motor function was evaluated using the short form of the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2) at the age of 11 years. We used Weighted Quartile Sum (WQS) regression models to examine the effect of phthalate metabolites in males and females separately. The models were adjusted for child age in months, child BMI, maternal race (African-American vs. Dominican), prenatal alcohol consumption, maternal demoralization score, HOME score, and urine specific gravity. In a secondary analysis we used linear regression models to examine the association between the sum of molar concentrations of both DEHP and non-DEHP metabolites, and outcomes of gross and fine motor functions. RESULTS: 209 mother-child pairs were eligible for this analysis. A significant decrease in fine-motor functions was observed among females, but not among males, following exposure to high levels of weighted quartile sum of seven phthalate metabolites (Covariates-adjusted coefficient estimate B = -2.7, 95% Confidence Interval [CI] -4.64 to -0.75, p = 0.01 for females [n = 116] and B = -1.63, 95%CI -3.94 to 0.69, p = 0.16 for males [n = 93]). The most highly weighted phthalate metabolites, associated with fine-motor functions among females, were MBP, MBZP, and MIBP, all non-DEHP phthalates. No significant associations were found between the weighted quartile sum of seven phthalate metabolites and gross-motor functions at the age of 11 years for males (B = -0.81, 95%CI -1.17 to 1.96, p = 0.23). With the molar sum of four non-DEHP phthalates as main predictor of linear regression models, we found significant decrease in gross and fine motor functions among females prenatally exposed to non-DEHP phthalates B = -0.98, 95%CI -1.98 to 0.03, p = 0.05 and B = -0.85, 95%CI -1.49 to -0.20, p = 0.01, respectively). CONCLUSIONS: Phthalate exposure during pregnancy was associated with decreased motor functions among 11-year-old girls.

The safety of amoxicillin and clavulanic acid use during the first trimester of pregnancy.

AIMS: The goal of the current study was to assess the risk for major congenital malformations following first-trimester exposure to amoxicillin, or amoxicillin and clavulanic acid (ACA). METHODS: A population-based retrospective cohort study was conducted, by linking 4 computerized databases: maternal and infant hospitalization records, drug dispensing database of Clalit Health Services in Israel and data concerning pregnancy terminations. Multivariate negative-binomial regression was used to assess the risk for major malformations following first-trimester exposure, adjusted for mother's age, ethnicity (Bedouin vs Jewish), parity, diabetes mellitus, lack of perinatal care, and the year of birth. RESULTS: The study included 101 615 pregnancies, of which 6919 (6.8%) were exposed to amoxicillin: 1045 (1.0%) to amoxicillin only and 6041 (5.9%) to ACA. No significant association was found, in the univariate and multivariate analyses, between first-trimester exposure to amoxicillin or ACA and major malformations in general (crude relative risk, 1.05 95% confidence interval 0.95-1.16; adjusted relative risk 1.09, 95% confidence interval 0.98-1.20), or for major malformations according to organ systems. No dose-response relationship was found between exposure in terms of the defined daily dose and major malformations. CONCLUSION: Exposure to amoxicillin and ACA during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations.

Pregnancy outcome following opioid exposure: A cohort study.

INTRODUCTION: Opioids constitute a cornerstone of pain relief treatment. However, opioid safety during pregnancy has not been well established. Recent studies reported an association between in utero opioid exposure and spina bifida. METHODS: In order to further evaluate the association of opioids exposure during pregnancy with adverse pregnancy outcomes, we conducted a large historical cohort by linking four databases: medications dispensations, births, pregnancy terminations for medical reasons and infant hospitalizations during the years of 1999-2009. Confounders that were controlled for included maternal age, ethnicity, maternal diabetes, smoking status, parity, obesity, year and folic acid intake. A secondary analysis for total major malformations and for spina bifida was performed using propensity score matching for first trimester exposure. RESULTS: Of the 101,586 women included in the study, 3003 were dispensed opioids during the first trimester. Intrauterine exposure to opioids was not associated with overall major malformations (adjusted odds ratio (aOR) 0.97, 95% CI 0.83-1.13), cardiovascular malformations (aOR = 0.89, 95% CI 0.70-1.13) other malformations by systems or spina bifida in particular. However, the risk for spina bifida among newborns and abortuses who were exposed to codeine was four times higher than that of the unexposed (aOR = 4.42, 95% CI 1.60-12.23). This association remained significant in a secondary analysis using propensity score matching. Third trimester exposure to opioids was not associated with low birth weight (aOR = 1.08, 95% CI 0.77-1.52), perinatal death (aOR = 1.38, 95% CI 0.64-2.99) and other adverse pregnancy outcomes. CONCLUSIONS: These findings suggest that opioids exposure (as a homogenous group) is not a significant risk factor for overall major malformations. Exposure to codeine during the first trimester was found to be associated with increased risk of spina bifida. However, this finding was based on a small number of cases and need to be verified in future work.

Infection prevention control and organisational patient safety culture within the context of isolation: study protocol.

BACKGROUND: Healthcare associated infection (HCAI) is a major cause of morbidity and mortality. In recent years, there have been high profile successes in infection prevention control (IPC), such as the dramatic reductions in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (which is viewed as one proxy indicator of overall harm) and Clostridium difficile in the UK. Nevertheless, HCAI remains a costly burden to health services, a source of concern to patients and the public and at present, is receiving priority from policy makers as it contributes to the global threat of antimicrobial resistance. METHODS: The study involves qualitative case studies within isolation settings at two National Health Service (NHS) district general hospitals (DGHs) in Wales, in the UK. The 18-month study incorporates Manchester Patient Safety Framework (MaPSaF) workshops with health workers and other hospital staff, in depth interviews with patients and their relative / informal carer, health workers and hospital staff, and periods of hospital ward observation. DISCUSSION: The present study aims to investigate the ways in which engagement of health workers with IPC strategies and principles, shape and inform organisational patient safety culture within the context of isolation in surgical, medical and admission hospital settings; and vice-versa. We want to understand the meaning of IPC 'ownership' for health workers; the ways in which IPC is promoted, how IPC teams operate as new challenges arise, how their effectiveness is assessed and the positioning of IPC within the broader context of organisational patient safety culture, within hospital isolation settings.