Comparing traditional modeling approaches versus predictive analytics methods for predicting multiple sclerosis relapse.

OBJECTIVE: This study compared traditional statistical methods to different predictive analytics methods on the endpoint of multiple sclerosis (MS) relapse. STUDY SETTING: This is a secondary data analysis on four different MS Centers based on the third year of data, July 2019-June 2020. STUDY DESIGN: The parent study is a two-part, 3-year clinical quality improvement prospective study that started in June 2017 and concluded in June 2020, and utilizes a prospective stepped-wedge randomized design. Binary logistic regression was compared with other machine learning models, specifically ridge, least absolute shrinkage and selection operator (LASSO), and random forest. DATA COLLECTION: This study used electronic health record data extracted at the individual level and 'rolled up' to the system and population level. Inclusion criteria included participants aged 18 years or older, with MS presenting to any of the four centers, who entered the study in any quarter. Exclusion criteria included cases with missing or incorrectly input data and those who refused to participate in the study. PRINCIPAL FINDINGS: When comparing relapse indices across models, random forest significantly outperformed logistic regression and other machine learning algorithms (ΔperfA =27.1%, ΔperfM =27.5%). However, for ΔperfF, logistic regression and random forest performed relatively the same. Ridge and LASSO outperformed logistic regression (ΔperfM1 =0.9%, ΔperfM2 =9.4%, ΔperfF2=25.8%, respectively). CONCLUSION: Multiple sclerosis is a complex and costly chronic ("3C") condition that currently has no cure. In a condition like MS, which has an unpredictable course, the use of predictive analytics could help health systems learn better, faster, and to improve more effectively and predict rather than react to emerging health needs for people with MS. Comparing the predictability of relapse across various models with a predictive analytics framework can potentially change how we manage MS care.

Transabdominal cerclage placement in patients with prior uterine incisions: risk of scar disruption.

The object of this study was to describe pregnancy outcomes in women who had a transabdominal cerclage (TAC) placed after a prior uterine incision due to caesarean section or hysterotomy. This is a retrospective observational study of 57 women referred to a maternal-fetal medicine specialist (JES) for TAC placement after a previous uterine incision from 1989-2012. Pregnancy outcomes post-TAC placement are reported, including gestational age at delivery, survival rate and complications directly related to labour and the previous uterine scar. Of 51 women who had a prior uterine incision and were pregnant at TAC, 49 (96.1%) delivered viable infants at a mean gestational age of 35.9 weeks. One patient had intrauterine fetal demise at 16 weeks for causes likely unrelated to TAC and another had uterine rupture associated with a unicornuate uterus and advancing labour at 31 weeks. This study includes women with low transverse incisions, classical uterine incisions and higher order multiples. It was concluded that in women with a prior uterine incision, placement of a TAC is associated with low risk (2%) of uterine rupture.

Timing of prophylactic antibiotic at cesarean section: a double-blinded, randomized trial.

OBJECTIVE: The purpose was to determine the effect of the timing of prophylactic antibiotics for cesarean section on post-operative infectious complications. STUDY DESIGN: This was a prospective, double-blinded, randomized controlled trial in which patients were randomized to receive cefazolin or clindamycin either before skin incision or after cord clamp. The primary outcome was maternal infectious morbidity at 6 weeks postpartum, a composite infectious outcome, which included endometritis, urinary tract infection, wound infection and pneumonia. RESULT: Data on 896 women were analyzed; 449 randomized to skin incision, 447 to cord clamp. Postpartum infections were seen in a total of 8.4% of patients. Timing of antibiotic administration did not significantly affect any maternal postpartum infection rates or selected neonatal outcomes. CONCLUSION: Our results suggest that, in a largely non-laboring population, the timing of prophylactic antibiotic administration does not impact post-operative infectious complications of the mother. Despite being one of the largest randomized controlled trials to address this question, our study still lacked sufficient power to make definitive conclusions.

Vasoconstriction in horses caused by endophyte-infected tall fescue seed is detected with Doppler ultrasonography.

The hypotheses that endophyte (Neotyphodium coenophialum)-infected tall fescue (TF) seed causes vasoconstriction in horses in vivo and that ground seed would cause more pronounced vasoconstriction than whole seed were tested. Ten horses each received 1 of 3 treatments: endophyte-free ground (E-G; n = 4 horses) seed, endophyte-positive whole (E+W; n = 3) seed, or endophyte-positive ground (E+G; n = 3) seed. There were two 14-d periods, P1 and P2. During P1, animals were adapted to a concentrate (0.2% BW, as fed, twice daily) and alfalfa cubes. During P2, the seed was mixed into the concentrate portion of the diet and alfalfa cubes were offered ad libitum. Fescue seed was fed in increasing amounts ranging from 0.02% BW on d 1 (averaging 76 ug/kg ergovaline + ergovalinine) to 0.22% BW on d 11 to 14 (averaging 713 ug/kg ergovaline + ergovalinine). The distal palmar artery of the left foreleg of each horse was scanned via Doppler ultrasonography for 4 d during each period, with 5 replicate scans performed on each scanning day. The measurements taken at each scan included artery luminal diameter, area, and circumference, peak systolic velocity, end diastolic velocity and blood flow variables. Animal temperature, heart rate, and respiration rate and ambient temperature and humidity were also recorded. Blood samples were taken on each scanning day to measure inflammatory cytokine mRNA abundances, and blood samples were collected on d 0, 4, 8, and 14 of P2 to measure prolactin concentrations. Consumption of E+G TF seed caused decreased artery lumen diameter (P = 0.0033), area (P = 0.0406), and circumference (P = 0.0480) compared with E-G seed, and E+W seed produced an intermediate response. Blood flow volume was reduced (P < 0.05) during P2 in horses receiving E+G seed compared with horses receiving E-G seed. Other ultrasound variables were not different (P > 0.05) among treatment groups, and neither were cytokine mRNA or prolactin concentrations. Treatment did not alter (P > 0.05) animal temperature, heart rate, or respiration rate, and neither ambient temperature nor relative humidity was consistently correlated with any response variable measured. Taken together, these data confirm that consumption of E+G fescue seed caused vasoconstriction in horses, which could be readily measured by Doppler ultrasonography. Use of Doppler ultrasound to monitor the diameter of the palmar artery of horses grazing endophyte-infected (E+) fescue pastures may provide a convenient and satisfactory biomarker to determine premonitory signs of fescue toxicosis.

Robotic-assisted transabdominal cerclage (RoboTAC) in the non-pregnant patient.

The use of cerclage, either through vaginal or abdominal routes, to assist in delaying pre-term delivery among select women with cervical insufficiency may be beneficial, but can also carry significant morbidity. Robotic-assisted transabdominal cervical cerclage (RoboTAC) in the non-pregnant patient has the ability to not only reduce associated morbidity, but also offer the same benefits as the more traditional laparotomy and laparoscopic approaches, while removing the risk to an in situ fetus. We report the use of robotic-assisted transabdominal cervical cerclage in 24 non-pregnant women. Feasibility of the procedure is discussed along with a description of the technical surgical details. In addition, limited pregnancy outcomes are presented. Our results suggest that RoboTAC is a safe alternative to the traditional laparotomy procedure with quicker recovery time.

Operative complications and fetal morbidity encountered in 300 prophylactic transabdominal cervical cerclage procedures by one obstetric surgeon.

This retrospective cohort study identifies complications associated with transabdominal cerclage (TAC). In 300 procedures performed over a 24 year time span, 11 (3.7%) surgical complications were encountered. Fetal loss (prior to 20 weeks) occurred in 4.1% of pregnancies. The median estimated blood loss among patients was 100 ml, with blood loss sufficient to require transfusion only once. Considering patients with classical indications, the gestational age at delivery was greater (37 weeks) after TAC than in the latest pre-TAC pregnancy (24 weeks) (p < 0.001). Lower uterine dehiscence in four patients and uterine rupture in one, underscore the advisability of early term delivery after fetal lung maturity is assured. A survival rate of 98.0% was calculated among infants that were delivered at >24 weeks' gestation. Our results demonstrate that complications encountered in placing a TAC were unusual and generally manageable. This communication may assist the surgeon to balance risks in individual clinical circumstances more adequately.

Transabdominal cervical cerclage in triplet pregnancies and risk of extreme prematurity and neonatal loss.

There are no reports indicating the effect of prophylactic transabdominal cerclage (TAC) on the prolongation of multifetal pregnancies. We report the use of TAC in triplets, which evolved over 20 years in one practice. A retrospective cohort study of triplet pregnancies was conducted. Obstetric and neonatal outcomes were compared among women who underwent a prophylactic TAC or transvaginal cerclage and no cerclage. Of the 141 women who delivered triplets, prophylactic TAC was associated with reduced incidence of extreme prematurity and improved incidence of neonatal/postnatal survival. With the exception of mode of conception, prepregnancy weight, and the use of home monitoring uterine activity monitor, procardia and terbutaline, no major differences were found in terms of patient characteristics and pregnancy and delivery management among the three groups. It was concluded that in triplet pregnancies, prophylactic placement of a TAC appears to lower the incidence of delivery before 28 weeks.

Automated diagnosis of fetal alcohol syndrome using 3D facial image analysis.

OBJECTIVES: Use three-dimensional (3D) facial laser scanned images from children with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis technique that can reliably and accurately identify individuals prenatally exposed to alcohol. METHODS: A detailed dysmorphology evaluation, history of prenatal alcohol exposure, and 3D facial laser scans were obtained from 149 individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern recognition techniques were used to automatically identify a set of facial features that best discriminated individuals with FAS from controls in each sample. RESULTS: An automated feature detection and analysis technique was developed and applied to the two study populations. A unique set of facial regions and features were identified for each population that accurately discriminated FAS and control faces without any human intervention. CONCLUSION: Our results demonstrate that computer algorithms can be used to automatically detect facial features that can discriminate FAS and control faces.

Effect of frequency and amount of rumen-degradable intake protein supplementation on urea kinetics and microbial use of recycled urea in steers consuming low-quality forage.

We evaluated the effect of frequency and amount of rumen-degradable intake protein (DIP) on urea kinetics in steers consuming prairie hay. Five ruminally and duodenally fistulated steers (366 kg of BW) were used in a 5 x 5 Latin square and provided ad libitum access to low-quality prairie hay (4.7% CP). Casein was provided daily in amounts of 61 and 183 mg of N/kg of BW (61/d and 183/d) and every third day in amounts of 61, 183, and 549 mg of N/kg of BW per supplementation event (61/3d, 183/3d, and 549/3d). Periods were 18-d long with 9 d for adaptation and 9 d for collection. Steers were in metabolism crates for total collection of urine and feces. Jugular infusion of (15)N(15)N-urea followed by determination of urinary enrichment of (15)N(15)N-urea and (14)N(15)N-urea was used to determine urea kinetics. Treatment means were separated to evaluate the effects of increasing DIP supplementation and the effects of frequency at the low (61/d vs. 183/3d) and at the high (183/d vs. 549/3d) amounts of DIP provision. Forage OM and total digestible OM intakes were linearly (P < or = 0.05) increased by increasing DIP provision but were not affected by frequency of supplementation at either the low or high amounts. Production and gut entry of urea linearly (P < or = 0.006) increased with DIP provision and tended to be greater (P < or = 0.07) for 549/3d than 183/d but were not different between 61/d and 183/3d. Microbial N flow to the duodenum was linearly (P < 0.001) increased by increasing DIP provision. Additionally, 183/d resulted in greater (P = 0.05) microbial N flow than 549/3d. Incorporation of recycled urea-N into microbial N linearly (P = 0.04) increased with increasing DIP. Microbial incorporation of recycled urea-N was greater for 549/3d than 183/d, with 42 and 23% of microbial N coming from recycled urea-N, respectively. In contrast, there was no difference due to frequency in the incorporation of recycled urea-N by ruminal microbes at the low level of supplementation (i.e., 61/d vs. 183/3d). This study demonstrates that urea recycling plays a substantial role in the N supply to the rumen and to the animal, particularly in steers supplemented infrequently with high levels of protein.

The effects of feeding flaxseed during the receiving period on morbidity, mortality, performance, and carcass characteristics of heifers.

Two experiments were conducted at the Kansas State University Beef Cattle Research Center to determine the effects of feeding ground flaxseed (flax) during the receiving period on the growth, health, and subsequent finishing performance of heifers. Crossbred heifers (Exp. 1: n = 363, 214 +/- 1 kg of initial BW; Exp. 2: n = 377, 222 +/- 1 kg of initial BW) were purchased during January and April of 2006. Heifers were fed receiving rations based on steam-flaked corn with 0, 2, 4, or 6% ground flax (DM basis) for 56 d. Following the receiving period, cattle in Exp. 1 and 2 were fed steam-flaked corn-based diets for 150 and 147 d, respectively, and then slaughtered. Heifers were implanted 91 and 109 d before slaughter for Exp. 1 and 2, respectively. In Exp. 1, DMI during the receiving period tended to increase linearly (P = 0.09) with increasing flax in the diet. Average daily gain was 1.46, 1.56, 1.58, and 1.61 kg for heifers fed 0, 2, 4, and 6% flax, respectively (linear, P = 0.03). Final BW in Exp. 1 after the finishing period was increased (linear, P = 0.04) with increasing inclusion of flax in the receiving diets. In Exp. 2, growth performance and mortality during the receiving period were not different among treatments (P > 0.12). During the receiving period in Exp. 2, incidence of the first respiratory treatment tended to be greatest (P = 0.09) for heifers fed 4% flax. During the finishing period, DMI were 8.4, 8.4, 8.0, and 8.1 kg/d for 0, 2, 4, and 6% flax, respectively (linear, P = 0.05). In Exp. 2, LM areas were greatest (quadratic, P = 0.04) for cattle fed 2% flax at receiving. In general, feeding flax during the receiving period may have the potential to improve growth performance; however, performance between experiments was variable, and many factors excluding flax feeding may have contributed to this response.

Effects of energy supply on leucine utilization by growing steers at two body weights.

The effects of energy supplementation on Leu utilization in growing steers were evaluated in 2 experiments by using 6 ruminally cannulated Holstein steers. In Exp. 1, steers (initial BW = 150 +/- 7 kg) were limit-fed (2.3 kg of DM/d) a diet based on soybean hulls and received a basal ruminal infusion of 100 g of acetate/d, 75 g of propionate/d, and 75 g of butyrate/d, as well as abomasal infusions of 200 g of glucose/d and a mixture (215 g/d) containing all essential AA except Leu. Treatments were arranged as a 3 x 2 factorial, with 3 amounts of Leu infused abomasally (0, 4, and 8 g/d) and supplementation of diets with 2 amounts of energy (0 and 1.9 Mcal/d of GE). Supplemental energy was supplied by ruminal infusion of 100 g of acetate/ d, 75 g of propionate/d, and 75 g of butyrate/d, as well as abomasal infusion of 200 g of glucose/d to provide energy to the animal without affecting the microbial protein supply. When no supplemental energy was provided, Leu supplementation increased N balance, with no difference between 4 and 8 g/d of Leu (24.5, 27.0, and 27.3 g/d for 0, 4, and 8 g/d of Leu), but when additional energy was supplied, N retention increased linearly in response to Leu (25.6, 28.5, and 31.6 g/d for 0, 4, and 8 g/d of Leu; Leu x energy interaction, P = 0.06). The changes in N balance were the result of changes in urinary N excretion. The greater Leu retentions in response to energy supplementation when Leu was the most limiting nutrient indicate that energy supplementation improved the true efficiency of Leu utilization. In addition, supplemental energy increased the gross efficiency of Leu utilization when the Leu supply was not limiting by increasing the maximal rates of protein deposition. Experiment 2 was similar to Exp. 1, but steers had an initial BW of 275 +/- 12 kg and were limit-fed at 3.6 kg of DM/d. Retention of N was not affected (P = 0.22) by Leu supplementation, indicating that Leu did not limit protein deposition. Energy supply increased N retention (P < 0.01) independently of Leu supplementation (33.0 vs. 27.8 g/d). Overall, energy supplementation improved Leu utilization by modestly increasing N retention when Leu was limiting and by increasing the ability of steers to respond to the greatest amount of supplemental Leu. We conclude from these results that the assumption of a constant efficiency of AA utilization is unlikely to be appropriate for growing steers.

Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine.

Break-through symptoms (BTS) in multiple sclerosis (MS) patients on beta-interferon (beta-IFN) monotherapy are most frequently treated with a brief administration of steroids. Here, we report the results of monitoring serum immunologic markers recorded at three-month intervals for 1.5 years in responders to beta-INF 1a (Avonex) monotherapy (n =21) and MS patients placed on Avonex with prednisone (n =83) and Avonex, prednisone and azathioprine (AZA) (n =21) because of BTS. Compared to 23 healthy controls, patients on Avonex monotherapy and Avonex with prednisone, in individuals on Avonex, prednisone and AZA, a significant decrease in serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (P=0.001) was established. Combined therapy with Avonex, prednisone and AZA was associated with a significant increase in the serum level of interleukin (IL)10 (P <0.001). Compared to Avonex monotherapy, combined therapy suppressed the serum level of IL12p40, antagonized elevation in the serum concentration of soluble IL2 receptor (sIL2R) and inhibited an increase in the serum soluble CD95 (sCD95) molecule. In patients studied, no significant differences in the serum level of IL18 and tumor necrosis factor-alpha (TNF-alpha) were established. These findings are important in understanding some of the immunoregulatory mechanisms induced by combined therapy in MS.

The subtle facial signs of prenatal exposure to alcohol: an anthropometric approach.

OBJECTIVES: The purpose was to demonstrate that an objective, multivariate case definition of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) can be derived by means of craniofacial anthropometry. STUDY DESIGN: Craniofacial measurements (n = 21) were taken of 100 individuals who had been exposed to alcohol before birth (41 FAS, 59 PFAS) and 31 members of a control group. Multivariate discriminant analysis was used to identify craniofacial measurements that best differentiated the 3 groups (FAS, PFAS, and control). RESULTS: Both the FAS and PFAS groups had a unique craniofacial phenotype that could be accurately discriminated from that of the control group. Stepwise discriminant analysis identified 6 craniofacial measurements that could differentiate individuals with and without prenatal alcohol exposure with 96% accuracy, 98% sensitivity, and 90% specificity. CONCLUSIONS: Individuals with FAS and PFAS have a distinctive facial phenotype that can be characterized anthropometrically. The phenotypic case definition could be used as a screening tool to identify individuals prenatally exposed to alcohol who do not exhibit a "classic" FAS phenotype but exhibit a more subtle craniofacial dysmorphia.

Recurrent abdominal and flank pain in children with idiopathic hypercalciuria.

OBJECTIVE: To evaluate the role of idiopathic hypercalciuria (IH) as a cause of recurrent abdominal pain (RAP) in children. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 124 children referred for various complaints who had 24-h urine calcium excretion greater than 2 mg/kg/d or random urine calcium-creatinine ratio greater than 0.18 mg/mg. RESULTS: Fifty-two children with various clinical complaints had RAP or flank pain. These comprised of 22 males and 30 females, 9 mo to 15.9 y of age, mean 6.7 +/- 3.5 y. A family history of urolithiasis was present in 50% of all the children. Only 6 of the 52 children with abdominal pain had renal stones. In addition to abdominal pain, 27 children had hematuria and 10 had urinary incontinence. Mild metabolic acidosis was present in three children, parathyroid hormone activity elevated in two and serum vitamin D activity was increased in nine. All children were treated with increased fluid intake and a reduction in dietary sodium and oxalate and some required treatment with thiazide and antispasmodics. Forty-five cases responded to treatment, 5 failed to improve from therapy, and 2, which were not followed up as patients, were not available. CONCLUSION: We describe 52 children with RAP or back pain due to IH and recommend that IH be considered in the differential diagnosis of RAP in childhood.

Urinary tract infection in children associated with idiopathic hypercalciuria.

OBJECTIVE: The aim of this study was to evaluate the association of symptomatic non-calculous idiopathic hypercalciuria (IH) with urinary tract infection (UTI) in children. MATERIAL AND METHODS: This was a retrospective case review of children who had urinary calcium excretion greater than 2 mg/kg/day or random urine calcium-creatinine ratio (UCa/UCr) greater than 0.18 mg/mg. RESULTS: One hundred and twenty-four consecutive children with clinical complaints and elevated urine calcium excretion were reviewed. Fifty children (40%) had UTI of which 39 (78%) had recurrent UTI. There was no difference in age between children with UTI and those without UTI. Twenty-four-hour urine calcium and random UCa/UCr were also not different. Only 4 children (8%) had renal stones whereas hematuria, abdominal pain and urine incontinence were frequent associated findings. Six of the children with recurrent UTI (15%) had an anatomical urinary tract abnormality. Therapy in all children consisted of increased fluid intake and reduction in diet sodium and oxalate; however, 14 of the 39 children with recurrent UTI (36%) required therapy with a thiazide diuretic. Recurrent UTI was abolished in 24 children, one child had a single recurrence and 4 children had no response to treatment. CONCLUSIONS: We propose that non-calculous IH may be an important contributing factor to recurrent UTI in children.

Urinary calcium excretion in healthy Thai children.

The objective of this study was to determine age-specific reference values for urinary calcium/creatinine ratios (UCa/Cr) of children in southern Thailand. Non-fasting urine samples were collected from a random population of 488 healthy children (282 males, 206 females) ranging in age from 17 days to 15 years. Samples were divided into six groups by age. Subjects whose calcium levels exceeded the 95th percentile within each age group were classified as having hypercalciuria. Pyuria, hematuria, proteinuria, urinary sodium, and potassium levels in children with normal UCa/Cr were compared with levels in children with high UCa/Cr. The 95th percentiles for UCa/Cr (mg/mg) by age were: <6 months, 0.75; 6 months to <12 months, 0.64; 12 months to <2 years, 0.40; 2 years to <5 years, 0.38; 5 years to <10 years, 0.29; and 10 years to <15 years, 0.26. Pyuria, hematuria, and proteinuria were no more prevalent in the 22 children with hypercalciuria than in children with normal urinary calcium levels. Urinary sodium/creatinine ratios (UNa/Cr) and urinary sodium/potassium ratios (UNa/K) were correlated with UCa/Cr (r=0.41, P<0.0001 and r=0.24, P<0.0001, respectively). Urinary potassium/creatinine ratios (UK/Cr) were not (r=0.05, P>0.1)). Children with high UCa/Cr ratios also had higher UNa/Cr and UNa/K (5.6+/-7.1 vs. 2.6+/-1.5, P<0.001 and 5.4+/-2.3 vs. 2.5+/-0.23, P<0.05, respectively). The study established reference values for random, non-fasting UCa/Cr for healthy Thai children and indicated that urinalysis is not a good indicator of hypercalciuria.

Heterogeneity in Wiedemann-Beckwith syndrome: anthropometric evidence.

Wiedemann-Beckwith syndrome (WBS) has attracted a great deal of attention because of its genetic complexity. Individuals with WBS can be identified objectively by anthropometric analysis. Craniofacial anthropometry in conjunction with multivariate statistical analysis can be used to define patterns of variability that appear to relate to specific modes of inheritance that have been proposed for WBS. Our data on 19 affected individuals and their first-degree relatives indicate that the pattern of inheritance rather than the age of subjects may be responsible for the highly variable craniofacial phenotype found in individuals diagnosed with WBS.

Angiogenesis and macrophage activation in endometriosis.

Recent studies suggest that the symptoms associated with endometriosis are the result of local peritoneal inflammation. Increased concentrations of activated pelvic macrophages and lymphocytes and the elevated levels of specific cytokines and growth factors reviewed above support this hypothesis. The precise roles of these soluble factors are currently unknown, but we propose that a complex network of endometrial cytokines are normally regulated by hormones produced during the ovulatory cycle. Ectopic endometrial implants also are subject to these same endocrine cues. The secretion of these proinflammatory proteins by endometriosis lesions into the peritoneal microenvironment appears to cause a recruitment of capillaries and activated inflammatory cells to the implant. Future therapeutic strategies directed to ameliorate the inflammatory reaction associated with endometriosis should not ignore the likely physiological actions of many of the same bioactive molecules in normal eutopic endometrial function.