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.

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.

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.

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.

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.

Seasonality of birth affects paediatric coeliac disease.

AIM: This study investigated the seasonality of birth in children diagnosed with coeliac disease (CD) at a tertiary University hospital in Southern Israel. METHODS: This was a population-based retrospective time series analysis study from January 1988 to December 2014. There were 308 903 live births at Soroka University Medical Centre during the study period and 699 were diagnosed with CD. We combined three databases covering births, CD diagnoses and weather indices. The daily proportion of births that resulted in CD for the different four seasons and high seasons were compared to the weather indices on the day of birth using negative binomial regression. RESULTS: Statistically significant associations were found between the season of birth and the rate of CD, with autumn births being associated with a higher risk for the development of CD than births during the summer, with an incidence ratio of 1.22. The association was further increased when the defined summer and autumn high seasons were used, with an incidence ratio of 1.40. No association was found between CD and the mean temperature and global radiation. CONCLUSION: Coeliac disease was associated with birth during the autumn and the autumn high season posed an even more significant risk factor.

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.

Vaginal antimycotics and the risk for spontaneous abortions.

BACKGROUND: Spontaneous abortions are the most common complication of pregnancy. Clotrimazole and miconazole are widely used vaginal-antimycotic agents used for the treatment of vulvovaginal candidiasis. A previous study has suggested an increased risk of miscarriage associated with these azoles, which may lead health professionals to refrain from their use even if clinically indicated. OBJECTIVE: The aim of the current study was to assess the risk for spontaneous abortions following first trimester exposure to vaginal antimycotics. STUDY DESIGN: A historical cohort study was conducted including all clinically apparent pregnancies that began from January 2003 through December 2009 and admitted for birth or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Beer-Sheva, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. Time-varying Cox regression models were constructed adjusting for mother's age, diabetes mellitus, hypothyroidism, obesity, hypercoagulable or inflammatory conditions, recurrent miscarriages, intrauterine contraceptive device, ethnicity, tobacco use, and the year of admission. RESULTS: A total of 65,457 pregnancies were included in the study: 58,949 (90.1%) ended with birth and 6508 (9.9%) with a spontaneous abortion. Overall, 3246 (5%) pregnancies were exposed to vaginal antimycotic medications until the 20th gestational week: 2712 (4.2%) were exposed to clotrimazole and 633 (1%) to miconazole. Exposure to vaginal antimycotics was not associated with spontaneous abortions as a group (crude hazard ratio, 1.11; 95% confidence interval, 0.96-1.29; adjusted hazard ratio, 1.11; 95% confidence interval, 0.96-1.29) and specifically for clotrimazole (adjusted hazard ratio, 1.05; 95% confidence interval, 0.89-1.25) and miconazole (adjusted hazard ratio, 1.34; 95% confidence interval, 0.99-1.80). Furthermore, no association was found between categories of dosage of vaginal antimycotics and spontaneous abortions. CONCLUSION: Exposure to vaginal antimycotics was not associated with spontaneous abortions.

Immortal time bias in drug safety cohort studies: spontaneous abortion following nonsteroidal antiinflammatory drug exposure.

OBJECTIVE: Experimental research of drug safety in pregnancy is generally not feasible because of ethical issues. Therefore, most of the information about drug safety in general and teratogenicity in particular is obtained through observational studies, which require careful methodologic design to obtain unbiased results. Immortal time bias occurs when some cases do not "survive" sufficient time in the study, and as such, they have reduced chances of being defined as "exposed" simply because the durations of their follow-ups were shorter. For example, studies that examine the risk for spontaneous abortions in women exposed to a drug during pregnancy are susceptible to immortal time bias because the chance of drug exposure increases the longer a pregnancy lasts. Therefore, the drug tested may falsely be found protective against the outcome tested. The objective of the current study was to illustrate the extent of immortal time bias using a cohort study of pregnancies assessing the risk for spontaneous abortions following nonsteroidal antiinflammatory drug exposure. STUDY DESIGN: We assembled 3 databases containing data on spontaneous abortions, births and drug dispensions to create the present study's cohort. The risk for spontaneous abortion was assessed using 2 statistical analysis methods that were compared for 2 definitions of exposure (dichotomous, exposed vs unexposed, regular Cox regression vs Cox regression with time-varying exposure). RESULTS: Significant differences were found in the risk for spontaneous abortions between the 2 statistical methods, both for groups and for most specific nonsteroidal antiinflammatory drugs (nonselective Cox inhibitors - hazard ratio, 0.70; 95% confidence interval, 0.61-0.94 vs hazard ratio, 1.10; 95% confidence interval, 0.99-1.22 for dichotomous vs time-varying exposure analyses, respectively). Furthermore, a significant correlation was found between the median misclassified immortal time for each drug and the extent of the bias. CONCLUSION: Immortal time bias can easily occur in cohort studies assessing the risk for adverse pregnancy outcomes following exposure to drugs. One way to prevent such a bias is by defining exposure only from the time of exposure during follow-up onward using a time-varying exposure analysis.

NSAIDs and spontaneous abortions - true effect or an indication bias?

AIM: The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain. METHODS: We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression. RESULTS: A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non- selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non-selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion. CONCLUSIONS: The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions.

Fetal exposure to nonsteroidal anti-inflammatory drugs and spontaneous abortions.

BACKGROUND: Spontaneous abortion is the most common complication of pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used during pregnancy. Published data are inconsistent regarding the risk of spontaneous abortion following exposure to NSAIDs. METHODS: We performed a historical cohort study involving all women who conceived between January 2003 and December 2009 and who were admitted for delivery or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. We constructed time-varying Cox regression models and adjusted for maternal age, diabetes mellitus, hypothyroidism, obesity, hypercoagulation or inflammatory conditions, recurrent miscarriage, in vitro fertilization of the current pregnancy, intrauterine contraceptive device, ethnic background, tobacco use and year of admission. RESULTS: The cohort included 65,457 women who conceived during the study period; of these, 58,949 (90.1%) were admitted for a birth and 6508 (9.9%) for spontaneous abortion. A total of 4495 (6.9%) pregnant women were exposed to NSAIDs during the study period. Exposure to NSAIDs was not an independent risk factor for spontaneous abortion (nonselective cyclooxygenase [COX] inhibitors: adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.99-1.22; selective COX-2 inhibitors: adjusted HR 1.43, 95% CI 0.79-2.59). There was no increased risk for specific NSAID drugs, except for a significantly increased risk with exposure to indomethacin (adjusted HR 2.8, 95% CI 1.70-4.69). We found no dose-response effect. INTERPRETATION: We found no increased risk of spontaneous abortion following exposure to NSAIDs. Further research is needed to assess the risk following exposure to selective COX-2 inhibitors.

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.

Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes.

OBJECTIVE: Despite high rates of hypertension in pregnancy, the effects of hypertension have not been separated appropriately from the effects of the medications that are used. We evaluated the safety of exposure to antihypertensive medications during pregnancy, while accounting for disease effects. STUDY DESIGN: A population-based retrospective cohort study was performed that compared all pregnancies of women with hypertension who were either exposed or unexposed to antihypertensive medications. A computerized database of the medications that were dispensed to pregnant women from 1998-2008 was linked with computerized databases that contained maternal and infant hospitalization records from the district hospital during the same period. RESULTS: During the study period, 100,029 deliveries occurred; of those, 1964 pregnant women experienced chronic hypertension, and 620 neonates (0.6%) were exposed to at least 1 antihypertensive medication (methyldopa or atenolol) during pregnancy. A higher rate of intrauterine growth restriction (7.2% vs 2.1%, respectively; adjusted odds ratio [OR], 4.37; 95% confidence interval [CI], 3.00-6.36; P < .001), small for gestational age (3% vs 1.7%, respectively; adjusted OR, 2.23; 95% CI, 1.27-3.92; P = .005), and preterm deliveries (<37 weeks, 22.9% vs 8.0%, respectively; adjusted OR, 3.69; 95% CI, 2.90-4.69; P < .001) were noted among the pregnancies of women who were exposed to antihypertensive medications during the third trimester. Importantly, a similar association was detected when we compared women with chronic hypertension who were not treated during pregnancy (n = 1074) to women who had no chronic hypertension and who were unexposed to antihypertensive medications (n = 97,820). CONCLUSION: Chronic hypertension with or without treatment during pregnancy is an independent and significant risk factor for adverse perinatal outcomes such as intrauterine growth restriction, small for gestational age, and preterm delivery.

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.

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.

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.