Validation of a modified obstetric comorbidity index for prediction of postpartum adverse events including fetal morbidity - a retrospective cohort study from Qatar.

BACKGROUND: The Obstetric Comorbidity Index (OBCMI) is an internationally validated scoring system for maternal risk factors intended to reliably predict the occurrence of severe maternal morbidity (SMM). This retrospective cohort study applied the OBCMI to pregnant women in Qatar to validate its performance in predicting SMM and cumulative fetal morbidity. METHODS: Data from 1000 women who delivered in July 2021 in a large tertiary centre was extracted from medical records. The OBCMI index included maternal demographics, pre-existing comorbidities, and various current pregnancy risk factors such as hypertension, including preeclampsia, intrauterine fetal death, prolonged rupture of membranes and unbooked pregnancies. SMM was based on the ACOG consensus definition, and the cumulative fetal morbidity (CFM) included fetal distress in labour, low APGAR and umbilical artery (UA) pH, admission to neonatal intensive care (NICU), and hypoxic-ischemic encephalopathy (HIE). A c-statistic or area under curve (AUC) was calculated to determine the ability of OBCMI to predict SMM and CFM. RESULTS: The median OBCMI score for the cohort was 1 (interquartile range- 0 to 2); 50% of women scored 0, while 85% (n = 842) had a score ranging from 0 to 2. Ten women (1%) scored ≥ 7; the highest score was 10. The incidence of SMM was 13%. According to the modified scoring system, the mean OBCMI score in those who developed SMM was 2.18 (± 2.20) compared to a mean of 1.04 (± 1.40) in those who did not (median 1, IQR:1-3 versus median 0, IQR: 0-2; p < 0.001). The incidence of CFM was 11.3%. The incidence of low APGAR score, HIE and NICU admission was nearly 1 in 1000. Around 5% of the babies had fetal distress in labour and low UA pH. For every 1 unit increase in OBCMI score, the odds of SMM increased by 44% (OR 1.44 95% CI 1.30-1.59; p < 0.001; AUC 0.66), and CFM increased by 28% (OR 1.28 95% CI 1.15-1.42; p < 0.001; AUC 0.61). A cut-off score of 4 had a high specificity (> 90%); 1 in 4 and 1 in 6 women with OBCMI score ≥ 4 developed SMM and CFM, respectively. CONCLUSION: The OBCMI performed moderately well in predicting SMM in pregnant women of Qatar and can be effectively used as a risk assessment tool to red-flag high-risk cases so that appropriate and timely multidisciplinary care can be initiated to reduce SMM and maternal mortality. The index is also helpful in predicting fetal morbidity; however, further prospective studies are required to validate OBCMI for CFM.

Time-resolved fluorescence and diffuse reflectance for lung squamous carcinoma margin detection.

OBJECTIVES: A major challenge in non-small cell lung cancer surgery is the occurrence of positive tumor margins. This may lead to the need for additional surgeries and has been linked to poor patient prognosis. This study aims to develop an in vivo surgical tool that can differentiate cancerous from noncancerous lung tissue at the margin. METHODS: A time-resolved fluorescence and diffuse reflectance bimodal device was used to measure the lifetime, spectra, and intensities of endogenous fluorophores as well as optical properties of lung tissue. The tumor and fibrotic tissue data, each containing 36 samples, was obtained from patients who underwent surgical removal of lung tissue after being diagnosed with squamous carcinoma but before any other treatment was administered. The normal lung tissue data were obtained from nine normal tissue samples. RESULTS: The results show a statistically significant difference between cancerous and noncancerous tissue. The results also show a difference in metabolic related optical properties between fibrotic and normal lung tissue samples. CONCLUSIONS: This work demonstrates the feasibility of a device that can differentiate cancerous and noncancerous lung tissue for patients diagnosed with squamous cell carcinoma.

Maternal and neonatal outcomes associated with multiple repeat cesarean deliveries: A registry-based study from Qatar.

BACKGROUND: Cesarean delivery (CD) is associated with increased maternal and neonatal morbidity compared to vaginal delivery, particularly in cases classified as emergency procedures or when there are multiple CDs. This retrospective cohort study aims to examine the incidence of maternal and neonatal complications in women with multiple CDs. METHODS: This study used data from a national perinatal database obtained from a single tertiary maternity care hospital. Women who delivered a singleton live birth after 24 weeks of gestation by CD were stratified into five groups based on the number of CDs, with the last group having five or more CDs. The women were divided into those with five or more CDs (Group 5) versus those with fewer than five (Groups 1 to 4). The maternal outcomes included intra-operative surgical complications, blood loss, and intensive care unit (ICU) admission. The neonatal outcomes included preterm birth, neonatal ICU (NICU) admission, respiratory distress syndrome (RDS), and perinatal death. RESULTS: Of the 6,316 women in the study, 2,608 (41.3%) had a primary CD. 30.3%, 17.5%, and 7.3% of the cohort had their second, third, and fourth CDs, respectively. Women undergoing the 5th CD and above formed the remaining 3.5% (227). Women in Group 5 had the highest risk of suffering a surgical complication (3.1%, p = 0.015) and postpartum hemorrhage (7.5%, p = 0.010). 24% of babies in Group 5 were born preterm (p < 0.001). They also had a 3.5 times higher risk of having a surgical complication (RR = 3.5, 95% CI 1.6-7.6, p = 0.002), a 1.8 times higher risk of developing postpartum hemorrhage (RR = 1.8, 95% CI 1.1-2.9, p = 0.014), a 1.7 times higher risk of delivering between 32-37 weeks of gestation (RR = 1.7, 95% CI 1.3-2.2, p < 0.001), a higher risk of the baby getting admitted to NICU (RR = 1.3, 95% CI 1.0-1.6, p = 0.038), and developing RDS (RR = 1.5, 95% CI 1.2-2.0, p = 0.002) compared to Groups 1-4. The risks of neonatal outcomes such as NICU admission (RR 2.9, 95% CI 2.1-4.0) and RDS (RR 3.5, 95% CI 2.3-5.5) were much higher in elective CDs performed at term compared to preterm births (p < 0.001 for both). CONCLUSION: Maternal morbidity significantly increases with the increasing number of CD. The increased risk of RDS and NICU admissions in the neonate with multiple CDs reflects lower gestational age and birthweight in these groups-consideration of preoperative steroids for lung maturation in these women to reduce neonatal morbidity warrants further discussion.

Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system.

OBJECTIVE: This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated. METHOD: In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue. RESULTS: Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification. CONCLUSION: With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.

The impact of abnormal maternal body mass index during pregnancy on perinatal outcomes: a registry-based study from Qatar.

OBJECTIVES: Abnormal body mass index (BMI) during pregnancy, a growing public health concern, increases maternal and neonatal complications. This study aimed to investigate the impact of abnormal BMI on perinatal outcomes compared to normal BMI. METHODS: A total of 14,624 women having singleton births were categorized as underweight (BMI<18.5 kg/m2), overweight (25.0-29.9 kg/m2), obesity class I (30.0-34.9 kg/m2), obesity class II (35.0-39.9 kg/m2), and obesity class III (≥40.0 kg/m2) and compared to those with normal BMI (18.5-24.9 kg/m2). Outcomes included gestational diabetes (GDM), gestational hypertension (GHT), postpartum haemorrhage (PPH), cesarean delivery (CD), preterm birth (PTB), low birth weight (LBW), congenital anomalies and neonatal intensive care unit admission. RESULTS: Women with increasing BMI had increasingly higher odds of developing specific adverse outcomes, the highest being in the class III obesity group (GDM-aOR 2.71, 95 % CI 2.25-3.27, p<0.001, GHT-aOR 5.32 95 % CI 3.49-8.11, p<0.001, CD-aOR 2.33 95 % CI 1.85-2.94, p<0.001, PPH-aOR 1.77 95 % CI 1.35-2.33, p<0.001). On the other hand, being underweight during pregnancy was associated with increased odds of PTB (aOR 2.09, 95 % CI 1.37-3.20, p=0.001), LBW (OR 1.88, 95 % CI 1.27-2.79, p=0.002) and congenital anomalies (aOR 2.52 95 % CI 1.12-5.64, p=0.025). Majority in the underweight category gained less than expected gestational weight gain during the pregnancy. CONCLUSIONS: The findings of this study have important implications for the clinical management of pregnant women with abnormal BMI. Interventions to improve maternal and neonatal outcomes must focus on enhancing pre-pregnancy BMI and maintaining adequate gestational weight gain.

Impact of the fear of Covid-19 infection on intent to breastfeed; a cross sectional survey of a perinatal population in Qatar.

OBJECTIVES: Infection control measures during the Covid-19 pandemic have focused on limiting physical contact and decontamination by observing cleaning and hygiene rituals. Breastfeeding requires close physical contact and observance of hygienic measures like handwashing. Worries around contamination increase during the perinatal period and can be expressed as increase in obsessive compulsive symptoms. These symptoms have shown to impact breastfeeding rates. This study attempts to explore any relationship between the Covid-19 pandemic and perinatal obsessive-compulsive symptomatology and whether the Covid-19 pandemic has any impact on intent to breastfeed. METHODS: A cross sectional survey of perinatal women attending largest maternity centre in Qatar was carried out during the months of October to December 2020. Socio-demographic information, intent to breastfeed and information around obsessive compulsive thoughts around Covid-19 pandemic were collected using validated tools. RESULTS: 15.7% respondents report intent to not breastfeed. 21.4% respondents reported obsessive-compulsive symptoms. 77.3% respondents believed the biggest source of infection was from others while as only 12% of the respondents believed that the source of infection was through breastfeeding and 15.7% believed the vertical transmission as the main source of risk of transmission. CONCLUSIONS: The rates of Obsessive-compulsive symptoms were increased and the rates of intent to breastfeed were decreased when compared with pre pandemic rates. The obsessive-compulsive symptoms and the intent to not breastfeed were significantly associated with fear of infection to the new-born. Obsessive-compulsive symptoms were not significantly correlated with intent to breastfeed and can be seen as adaptive strategies utilized by women to continue breastfeeding in the context of fear of infection.

Maternal risk factors of COVID-19-affected pregnancies: A comparative analysis of symptomatic and asymptomatic COVID-19 from the Q-PRECIOUS registry.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has had consequences on the pregnant population, as disease severity is associated with the quality of maternal health and pregnancy complications, increasing maternal and neonatal morbidity. Worldwide descriptive data help describe risk factors that could predict symptomatic and severe COVID-19 in pregnancy. OBJECTIVES: To describe demographic features and risk factors of pregnant women with COVID-19 in Qatar and compare symptomatic versus asymptomatic disease. STUDY DESIGN AND METHODOLOGY: Clinical characteristics and risk factors of pregnant women with COVID-19 in Qatar from March 2020 to March 2021 was retrospectively reviewed, comparing the cohort with the general pregnant population. Crude and adjusted odds ratios (aORs) were computed, comparing symptomatic versus asymptomatic infection. RESULTS: Of the 500 women, 347 reported at least one symptom at diagnosis (347/500; 69.4%). The majority fell in the 30-39 years age group (241/500; 48%), with more than half in the obese body mass index (BMI) category. The cohort was 66% (332/500) Qatari women, compared with the 26% expected in the population (26.4% vs 66.4% p < 0.001). Compared with the 2019 national statistics, the number of women was higher in the >40 years age group (5% vs 7.6%, p = 0.027) and grand multiparous group (5.4% vs 13.6%, p < 0.001). The symptom most commonly reported by the symptomatic group was cough (276/500; 55%), followed by fever, fatigue, and myalgia. In the adjusted analysis, the symptomatic group had 2.7 times higher odds of being asthmatic (OR = 2.67, 95% CI 1.1-6.7, p = 0.037). Women aged >40 years had 6.6 times higher odds of symptomatic disease (aOR = 6.6, 95% CI 1.08-39.73, p = 0.041). A history of contact with a patient with symptomatic COVID and earlier gestational age at diagnosis increased the odds (aOR = 2.06, 95% CI 1.2-3.54, p = 0.009; aOR = 0.73 95% CI 0.57-0.96; p = 0.017). CONCLUSIONS: This study cohort included significantly more Qatari women, older women, grand multiparous women, a higher proportion with pre-existing and gestational diabetes, and higher BMI than national data. In addition, contact to a patient with symptomatic disease, history of asthma, older age, and earlier gestational age at diagnosis were significantly associated with symptomatic disease.

GalaxyTrakr: a distributed analysis tool for public health whole genome sequence data accessible to non-bioinformaticians.

BACKGROUND: Processing and analyzing whole genome sequencing (WGS) is computationally intense: a single Illumina MiSeq WGS run produces ~ 1 million 250-base-pair reads for each of 24 samples. This poses significant obstacles for smaller laboratories, or laboratories not affiliated with larger projects, which may not have dedicated bioinformatics staff or computing power to effectively use genomic data to protect public health. Building on the success of the cloud-based Galaxy bioinformatics platform ( http://galaxyproject.org ), already known for its user-friendliness and powerful WGS analytical tools, the Center for Food Safety and Applied Nutrition (CFSAN) at the U.S. Food and Drug Administration (FDA) created a customized 'instance' of the Galaxy environment, called GalaxyTrakr ( https://www.galaxytrakr.org ), for use by laboratory scientists performing food-safety regulatory research. The goal was to enable laboratories outside of the FDA internal network to (1) perform quality assessments of sequence data, (2) identify links between clinical isolates and positive food/environmental samples, including those at the National Center for Biotechnology Information sequence read archive ( https://www.ncbi.nlm.nih.gov/sra/ ), and (3) explore new methodologies such as metagenomics. GalaxyTrakr hosts a variety of free and adaptable tools and provides the data storage and computing power to run the tools. These tools support coordinated analytic methods and consistent interpretation of results across laboratories. Users can create and share tools for their specific needs and use sequence data generated locally and elsewhere. RESULTS: In its first full year (2018), GalaxyTrakr processed over 85,000 jobs and went from 25 to 250 users, representing 53 different public and state health laboratories, academic institutions, international health laboratories, and federal organizations. By mid-2020, it has grown to 600 registered users and processed over 450,000 analytical jobs. To illustrate how laboratories are making use of this resource, we describe how six institutions use GalaxyTrakr to quickly analyze and review their data. Instructions for participating in GalaxyTrakr are provided. CONCLUSIONS: GalaxyTrakr advances food safety by providing reliable and harmonized WGS analyses for public health laboratories and promoting collaboration across laboratories with differing resources. Anticipated enhancements to this resource will include workflows for additional foodborne pathogens, viruses, and parasites, as well as new tools and services.

The intraoperative use of internal iliac artery balloon catheters in cesarean deliveries for abnormal invasive placentation: A 3-year retrospective cohort review in Doha, Qatar.

BACKGROUND: Abnormal invasive placentation leads to massive intraoperative hemorrhage and maternal morbidity. This study aimed to assess the impact of the preoperative use of internal iliac artery balloon occlusion (IIABO) catheters in patients who had a cesarean delivery (CD) for invasive placentation, commonly known as the placenta accreta spectrum. METHODS: This retrospective cohort study reviewed 67 pregnancies complicated by abnormal invasive placenta and confirmed intraoperatively. Preoperative planned placement of IIABO was performed in 33 women who underwent elective CD. Senior Obstetricians with the necessary expertise performed all CDs. The primary outcome measures were: intraoperative blood loss, blood transfusion requirement, duration of surgery and the need for hemostatic measures. Univariate comparison between the groups and regression analysis of the primary outcome and controlling for confounders, were performed. RESULTS: No statistically significant difference was observed between the groups with intraoperative hemorrhage volume of above 3000 mL (unadjusted odds ratio [OR] 0.94 [no-IIABO group as the reference]; p = 0.895) and the median duration of surgery (median 107, interquartile range [IQR] 80-135 vs. median 96, IQR 75-121; p = 0.3508). More than 40% of the IIABO group required intraoperative transfusion of packed red blood cells above six units (14 [42.4%] vs. 10 [29.4%]; p = 0.357]), and 30% required additional postoperative transfusion (10 [30.3%] vs. 8 [23.5%]; p = 0.706]), although not statistically significant. Multivariate logistic regression analysis showed that the difference remained nonsignificant after covariate adjustment (adjusted OR 0.585, p = 0.456). Cesarean hysterectomy was performed in fewer cases (seven [21.1%]) in the IIABO group than in the no-IIABO group (10 [29.4%]), although this difference was not significant (unadjusted OR 0.65, p = 0.442). CONCLUSIONS: The placement of IIABO catheters is an invasive procedure, which consumes time and resources. Its value as a means of reducing intraoperative blood loss or preserving the uterus in patients with abnormal placental adherence appears questionable. In this cohort study, there was no statistical difference in blood loss, and the need for other steps to control hemorrhage between women with and without IIABO catheters.

Time to Open Repair of Mandibular Fractures and Associated Complications.

PURPOSE: The aim of this study was to determine whether a correlation exists between the time from injury to repair of mandibular fractures and the development of postoperative complications. We also sought to assess whether a delay in treatment manifests in an increased surgical time. PATIENTS AND METHODS: We performed a retrospective cohort study and enrolled a sample (N = 64) derived from patients treated with open repair of mandibular fractures at Augusta University Medical Center by the oral and maxillofacial surgery service from July 2015 to June 2018. Time from injury to surgical repair was analyzed as a continuous variable, and the primary outcome was the presence of any of the following postoperative complications: infection, mechanical complication, cranial nerve V3 deficit, or cranial nerve VII deficit. Secondary outcome variables included the presence of substance abuse, surgical approach, and surgery time. Logistical regression was performed. RESULTS: Among 64 patients, there were 27 patients with a total of 32 complications, including infection (n = 9), mechanical complications (n = 3), cranial nerve V3 deficits (n = 13), and cranial nerve VII deficits (n = 7). The mean time to fixation was 13.26 days in patients without complications versus 17.52 days in patients with complications. The association between time to surgical repair and complication rate was not statistically significant (P = .203). No association was found between time to surgical repair and surgery time (P = .699). CONCLUSIONS: Our study did not find a significant association between the timing of repair of mandibular fractures and complications. Our study also failed to show a correlation between a delay in surgical intervention and increased technical challenges manifested by an increased surgical time.

Salicylate enhances the response of prostate cancer to radiotherapy.

BACKGROUND: Radiotherapy (RT) is a key therapeutic modality for prostate cancer (PrCa), but RT resistance necessitates dose-escalation, often causing bladder and rectal toxicity. Aspirin, a prodrug of salicylate (SAL), has been associated with improved RT response in clinical PrCa cases, but the potential mechanism mediating this effect is unknown. SAL activates the metabolic stress sensor AMP-activated protein kinase (AMPK), which inhibits de novo lipogenesis, and protein synthesis via inhibition of Acetyl-CoA Carboxylase (ACC), and the mammalian Target of Rapamycin (mTOR), respectively. RT also activates AMPK through a mechanism distinctly different from SAL. Therefore, combining these two therapies may have synergistic effects on suppressing PrCa. Here, we examined the potential of SAL to enhance the response of human PrCa cells and tumors to RT. METHODS: Androgen-insensitive (PC3) and -sensitive (LNCaP) PrCa cells were subjected to proliferation and clonogenic survival assays after treatment with clinically relevant doses of SAL and RT. Balb/c nude mice with PC3 xenografts were fed standard chow diet or chow diet supplemented with 2.5 g/kg salsalate (SAL pro-drug dimer) one week prior to a single dose of 0 or 10 Gy RT. Immunoblotting analysis of signaling events in the DNA repair and AMPK-mTOR pathways and lipogenesis were assessed in cells treated with SAL and RT. RESULTS: SAL inhibited proliferation and clonogenic survival in PrCa cells and enhanced the inhibition mediated by RT. Salsalate, added to diet, enhanced the anti-tumor effects of RT in PC3 tumor xenografts. RT activated genotoxic stress markers and the activity of mTOR pathway and AMPK and mediated inhibitory phosphorylation of ACC. Interestingly, SAL enhanced the effects of RT on AMPK and ACC but blocked markers of mTOR activation. CONCLUSIONS: Our results show that SAL can enhance RT responses in PrCa. Salsalate is a promising agent to investigate this concept in prospective clinical trials of PrCa in combination with RT.

Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer.

PURPOSE: One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical procedure. METHODS: A time-resolved fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure fluorescence intensity and lifetime as well as collect diffuse reflectance (DR) of breast tissue, which can subsequently be used to extract optical properties (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone lumpectomy and mastectomy surgeries is presented. A preliminary study was conducted to determine the validity of using banked pre-frozen breast tissue samples to study the fluorescence response and optical properties. Once the validity was established, the tr-FRS system was used on a data-set of 40 pre-frozen matched pair cases to differentiate between tumor and normal breast tissue. All measurements have been conducted on excised normal and tumor breast samples post surgery. RESULTS: Our results showed the process of freezing and thawing did not cause any significant differences between fresh and pre-frozen normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked matched pairs showed significant differences between normal and tumor breast tissue. CONCLUSION: The work detailed in the main study showed the tr-FRS system has the potential to differentiate malignant from normal breast tissue in women undergoing surgery for known invasive ductal carcinoma. With further work, this successful outcome may result in the development of an accurate intraoperative real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. © 2018 Wiley Periodicals, Inc.

Archaeological bone lipids as palaeodietary markers.

RATIONALE: Stable isotope analysis of archaeological and fossil bone samples can provide important insights into past environments, ecologies and diets. Previous studies have focused on stable carbon and nitrogen isotopes in bone collagen, or carbon isotopes in bone mineral (bioapatite). Carbon isotope analysis of lipids from archaeological bone has received much less attention, partly due to the lack of suitable methodologies allowing sufficient recovery of compounds for structural and isotopic characterisation. Here we show that lipids can be easily and reliably recovered from archaeological bone using a modified protocol, and that these provide complementary dietary information to other bone components. METHODS: Human and animal bones were obtained from a variety of archaeological contexts. Lipids were sequentially extracted using solvent extraction (dichloromethane/methanol), followed by acidified methanol extraction (methanol/H2SO4). The lipids were then analysed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). RESULTS: Appreciable amounts of endogenous lipid were recovered from archaeological bone. Importantly, a comparison between compound-specific and bulk collagen isotopic data shows that archaeological bone lipids reflect dietary input and can be used to distinguish between marine and terrestrial consumers, as well as between C3 and C4 plant consumers. Furthermore, the presence of essential fatty acids directly incorporated from diet to bone may provide additional palaeodietary information. CONCLUSIONS: Our findings suggest that archaeological bone lipids are a hitherto untapped resource of dietary information that offer additional insights to those gained from other isotopic analyses of bone.

Prophylactic intravenous ephedrine to minimize fetal bradycardia after combined spinal-epidural labour analgesia: a randomized controlled study.

BACKGROUND: The combined spinal-epidural (CSE) technique for relief of labour pain offers both rapid onset and superior first-stage analgesia. Nevertheless, the known increased risk for early profound fetal bradycardia (EPFB) following CSE continues to be a concern that often limits its use. The purpose of this study was to determine if giving prophylactic intravenous ephedrine at the time of CSE administration would reduce EPFB. METHODS: We conducted this clinical trial at a large community hospital and enrolled healthy patients requesting epidural analgesia for labour. Patients were randomly assigned to receive either normal saline placebo or ephedrine 10 mg iv at the time of CSE. The primary outcome of EPFB (defined as bradycardia < 90 beats·min(-1) for > two minutes and occurring within the first 30 min after CSE) was compared between groups. The secondary outcomes included the incidence of urgent cesarean delivery, the requirement for additional doses of ephedrine, maternal blood pressure, uterine hypertonus and tachysystole, and abnormal fetal heart rate (FHR) patterns before and after CSE. RESULTS: There were 299 women randomized to the ephedrine (EPH) group and 297 randomized to the normal saline placebo (NS) group. There was no difference between groups in the incidence of EPFB (2.7% EPH group vs 4.7% NS group; relative risk, 0.57; 95% confidence interval, 0.24 to 1.33; P = 0.184). There was also no difference between groups in the incidence of urgent cesarean delivery, uterine hypertonus, uterine tachysystole, and abnormal FHR patterns. CONCLUSIONS: We conclude that prophylactic intravenous ephedrine administration at the time of CSE during labour was ineffective at reducing the risk for EPFB associated with CSE. Nevertheless, a lower than expected rate of EPFB resulted in the trial being underpowered. This trial was registered at ClinicalTrials.gov, identifier: NCT02062801.

Fast simulation of Strehl loss due to phase aberration for the sizing of adaptive optics in laser communications system design.

An approximation is derived for the phase Strehl of an aberrated wavefront based on uncorrelated random variates. Eliminating the requirement to generate correlated variates offers an orders-of-magnitude improvement in simulation speed, while yielding accuracy that may be sufficient for the preliminary sizing of adaptive optics (AO) in laser communications system design. Examples are presented comparing the performance of several AO subsystem sizes when correcting a wavefront aberrated by Kolmogorov turbulence.

Investigation of critical core formulation and process parameters for osmotic pump oral drug delivery.

Push-pull osmotic pump (PPOP) tablets of a practically insoluble model drug were developed and the effect of various formulation and process parameters on tablet performance was evaluated in order to identify critical factors. The formulation factors such as the viscosity grade of polyethylene oxide as the primary polymer as well as the level and location of osmogen within the bilayer tablets led to a difference in performance of osmotic tablets and hence should be critically evaluated in the design of such dosage forms. Modification of granulation process, i.e., the granulating liquid composition or drying method of granules, did not impact the drug release from the osmotic tablets at the evaluated scale of this study. The influence of varying dose and aqueous solubility of other model drugs (i.e., theophylline, acetaminophen, and verapamil HCl) on the developed PPOP template was also investigated. Results showed that irrespective of the perceived complexity of development and manufacturing of osmotic pumps, the osmotic tablets in this study demonstrated a robust and yet flexible platform in accommodating different types of drug candidates, regardless of solubility, for the dose levels below 25% w/w of the pull layer formulation.

Patient perceptions of advanced practice radiation therapists prescribing medication in radiation therapy.

INTRODUCTION: The purpose of this study was to determine patient perceptions of an advanced practice radiation therapist (APRT) prescribing medication for radiation therapy treatment-related side effects. By comprehending patient perceptions, it is important to implement change in order to improve patients' quality of life. METHODS: A literature review was conducted on advanced practice (AP) roles in Canada and world-wide; the roles searched were: APRT, nurse practitioner and pharmacist. The search focused on evidence demonstrating improvements made to patient care due to the implementation of these roles. Based on this review and input from a team of experts a qualitative semi-structured interview survey was designed, and pilot tested. The survey consisted of five open-ended questions, which were designed to determine patient satisfaction of an APRT prescribing medication over the course of their radiation therapy treatments. Patients undergoing head and neck radiation therapy treatments at a large, academic cancer centre were invited to participate. Six patients who had a head and neck APRT involved in their treatment were interviewed. A comprehensive thematic analysis was then conducted using the transcripts created from these interviews, which was followed by two independent blinded analyses to ensure validity of the results. DISCUSSION: The thematic analysis produced four salient themes which were: side effect management, care provided by the APRT in comparison to other healthcare workers, patients' access to care, and overall patient satisfaction. Common medications for head and neck radiation therapy treatment related side effects were discussed and these were: Magic Mouthwash, Xylocaine, Nystatin, Benadryl, Advil, Tylenol, Dexamethasone, Tantum, Biotene, Mucaine, Flamazine, Hydrocortisone, Ondansetron, Senokot, and narcotics. CONCLUSION: This study was valuable to understand patient experiences and provide evidence to change processes in order to improve quality of patient centered care. The study revealed that although patients were happy with the process of prescribing medication, they all agreed that having an advanced practice radiation therapist prescribe would improve care. Patient responses further demonstrated the need for future research in regards to side effect management as a whole by APRTs as well as how role clarification can impact patient perceptions of APRTs.

Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach.

As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few "classic" CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care.

Perinatal outcomes in women with class IV obesity compared to women in the normal or overweight body mass index categories: A population-based cohort study in Qatar.

Background: The prevalence of childhood and adult obesity is rising exponentially worldwide. Class IV obesity (body mass index, BMI ≥50 kg/m2) is associated with a higher risk of adverse perinatal outcomes. This study compared these outcomes between women with class IV obesity and women in the normal or overweight categories during pregnancy. Methods: A retrospective cohort study was performed in Qatar, including women having singleton live births beyond 24 weeks of gestation, classified into two class IV obesity and normal/overweight (BMI between 18.5 and 30.0 kg/m2). The outcome measures included the mode of delivery, development of gestational diabetes and hypertension, fetal macrosomia, small for date baby, preterm birth and neonatal morbidity. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were determined using multivariable logistic regression models. Results: A total of 247 women with class IV obesity were compared with 6797 normal/overweight women. Adjusted analysis showed that women with class IV obesity had 3.2 times higher odds of cesarean delivery (aOR: 3.19, CI: 2.26-4.50), 3.4 times higher odds of gestational diabetes (aOR: 3.39, CI: 2.55-4.50), 4.2 times higher odds of gestational hypertension (aOR: 4.18, CI: 2.45-7.13) and neonatal morbidity (aOR: 4.27, CI: 3.01-6.05), and 6.5 times higher odds of macrosomia (aOR 6.48, CI 4.22-9.99). Conclusions: Class IV obesity is associated with more adverse perinatal outcomes compared with the normal or overweight BMI categories. The study results emphasized the need for specialized antenatal obesity clinics to address the associated risks and reduce complications.

Hypokinesia and reduced dopamine levels in zebrafish lacking ß- and γ1-synucleins.

α-Synuclein is strongly implicated in the pathogenesis of Parkinson disease. However, the normal functions of synucleins and how these relate to disease pathogenesis are uncertain. We characterized endogenous zebrafish synucleins in order to develop tractable models to elucidate the physiological roles of synucleins in neurons in vivo. Three zebrafish genes, sncb, sncg1, and sncg2 (encoding ß-, γ1-, and γ2-synucleins respectively), show extensive phylogenetic conservation with respect to their human paralogues. A zebrafish α-synuclein orthologue was not found. Abundant 1.45-kb sncb and 2.7-kb sncg1 mRNAs were detected in the CNS from early development through adulthood and showed overlapping but distinct expression patterns. Both transcripts were detected in catecholaminergic neurons throughout the CNS. Zebrafish lacking ß-, γ1-, or both synucleins during early development showed normal CNS and body morphology but exhibited decreased spontaneous motor activity that resolved as gene expression recovered. Zebrafish lacking both ß- and γ1-synucleins were more severely hypokinetic than animals lacking one or the other synuclein and showed delayed differentiation of dopaminergic neurons and reduced dopamine levels. Phenotypic abnormalities resulting from loss of endogenous zebrafish synucleins were rescued by expression of human α-synuclein. These data demonstrate that synucleins have essential phylogenetically conserved neuronal functions that regulate dopamine homeostasis and spontaneous motor behavior. Zebrafish models will allow further elucidation of the molecular physiology and pathophysiology of synucleins in vivo.