Maternal self-reported polycystic ovary syndrome with offspring and maternal cardiometabolic outcomes.

STUDY QUESTION: Do children born to mothers with polycystic ovary syndrome (PCOS) have an adverse cardiometabolic profile including arterial stiffness at 9 years of age compared to other children? SUMMARY ANSWER: Children of mothers with PCOS did not have differing cardiometabolic outcomes than children without exposure. WHAT IS KNOWN ALREADY: While women with PCOS themselves have higher risk of cardiometabolic conditions such as obesity and diabetes, the evidence on intergenerational impact is unclear. Given in utero sequalae of PCOS (e.g. hyperandrogenism, insulin resistance), the increased risk could be to both boys and girls. STUDY DESIGN, SIZE, DURATION: The Upstate KIDS cohort is a population-based birth cohort established in 2008-2010 to prospectively study the impact of infertility treatment on children's health. After ∼10 years of follow-up, 446 mothers and their 556 children attended clinical visits to measure blood pressure (BP), heart rate, arterial stiffness by pulse wave velocity (PWV), mean arterial pressure, lipids, high-sensitivity C-reactive protein (hsCRP), hemoglobin A1c (HbA1c), and anthropometrics. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women self-reported ever diagnoses of PCOS ∼4 months after delivery of their children in 2008-2010. Linear regression models applying generalized estimating equations to account for correlation within twins were used to examine associations with each childhood cardiometabolic outcome. MAIN RESULTS AND THE ROLE OF CHANCE: In this cohort with women oversampled on infertility treatment, ∼14% of women reported a PCOS diagnosis (n = 61). We observed similarities in BP, heart rate, PWV, lipids, hsCRP, HbA1c, and anthropometry (P-values >0.05) among children born to mothers with and without PCOS. Associations did not differ by child sex. LIMITATIONS, REASONS FOR CAUTION: The sample size of women with PCOS precluded further separation of subgroups (e.g. by hirsutism). The population-based approach relied on self-reported diagnosis of maternal PCOS even though self-report has been found to be valid. Participants were predominantly non-Hispanic White and a high proportion were using fertility treatment due to the original design. Differences in cardiometabolic health may be apparent later in age, such as after puberty. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide some reassurance that cardiometabolic factors do not differ in children of women with and without self-reported PCOS during pregnancy. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no conflicts of interest. REGISTRATION NUMBER: NCT03106493.

Predictors of Poor Functional Status in Adult Fontan Patients Living at Moderate Altitude.

Patients who have undergone Fontan palliation have reduced exercise tolerance measured by maximal oxygen consumption (VO2 max). Declining exercise capacity is associated with increased morbidity and mortality. The impact of hemodynamics and other variables on this population's functional status is not well understood. This study sought to identify variables that predict low VO2 max in Fontan patients living at moderate altitude (5,000-8,000 feet). We performed a retrospective cohort study of 44 adult Fontan patients living at moderate altitude who had undergone cardiopulmonary exercise testing (CPET) and cardiac catheterization. We evaluated hemodynamic parameters measured during catheterization, imaging results, and laboratory studies for correlation with VO2 max measured during CPET. Our study cohort (median age 30 years, 52% female) had exercise impairment with mean VO2 max of 21.6 mL/kg/min. Higher trans-pulmonary gradient (TPG) (p < 0.001) and mean pulmonary artery (PA) pressure (p = 0.013) were predictors of lower maximal and submaximal VO2. Higher BNP values correlated with lower VO2 max (p = 0.01). Platelet count, GGT, albumin, and pulmonary vasodilator therapy did not correlate with VO2 max. None of the studied variables were associated with higher minute ventilation to peak carbon dioxide production (VE/VCO2 slope) or change in VO2 max over time. In conclusion, higher TPG and mean PA pressure predicted lower exercise tolerance amongst our cohort of adult Fontan patients living at moderate altitude. Future studies are needed to determine if these clinical variables represent viable therapeutic targets that could result in improved exercise tolerance and outcomes in patients with Fontan circulation.

Infertility treatment and autism risk using the Modified Checklist for Autism in Toddlers (M-CHAT).

STUDY QUESTION: Are toddlers conceived by fertility treatment at higher risk of failing a screening tool for autism spectrum disorders (ASD) than toddlers not conceived by treatment? SUMMARY ANSWER: Compared with children not conceived by infertility treatment, children conceived by any infertility treatment, ovulation induction with or without intrauterine insemination (OI/IUI), or assisted reproductive technologies (ART) appeared to have had higher odds of failing an ASD screening; however, results were inconclusive and need replication. WHAT IS KNOWN ALREADY: Although most of the studies which have examined risk of ASD after ART show no association, the results are mixed. Thus, further studies are needed to clarify this association. STUDY DESIGN SIZE, DURATION: The Upstate KIDS Study is a population-based, prospective cohort study of children born in New York State between 2008 and 2010. Children were screened for ASD using the Modified Checklist for Autism in Toddlers (M-CHAT) at ages 18 and 24 months. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: The New York State live-birth registry was used to identify newborns conceived with and without fertility treatment with a 1:3 ratio, frequency matched on region of birth. At 18 and 24 months, 3183 and 3063 mothers, respectively, completed the M-CHAT questionnaire. The current analysis included 2586 singletons and 1296 twins with M-CHAT information at 18 and/or 24 months. Multivariable logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (aOR) and 95% confidence intervals (CI) after adjustment for covariates such as maternal age, education and plurality. MAIN RESULTS AND THE ROLE OF CHANCE: We found that 200 (5.2%) and 115 (3.0%) children failed the M-CHAT at 18 and 24 months, respectively. The associations between use of infertility treatment and failing the M-CHAT at 18 and/or 24 months were positive but inconclusive as they failed to exclude no association (18 months aOR 1.71, 95% CI: 0.81-3.61; 24 months aOR 1.78, 95% CI: 0.66-4.81; and both 18 and 24 months aOR 1.53, 95% CI: 0.78-2.99). The relationships between OI/IUI and ART with M-CHAT failure at 18 and/or 24 months were similar to those of using any fertility treatment. In vitro fertilization with intracytoplasmic sperm injection was not consistently positively or inversely associated with M-CHAT failure at each time point (18 months aOR 1.20, 95% CI: 0.51-2.83; 24 months aOR 0.93, 95% CI: 0.37-2.31; and both 18 and 24 months aOR 1.09, 95% CI: 0.50-2.60). LIMITATIONS REASONS FOR CAUTION: The M-CHAT is a screening tool used for ASD risk assessment, and therefore, M-CHAT failure does not indicate ASD diagnosis. In addition, we did not have power to detect associations of small magnitude. Finally, non-response to follow-up may bias the results. WIDER IMPLICATIONS OF THE FINDINGS: Despite lack of precision, the positive associations between ART and M-CHAT failure suggest that larger population-based studies with longer follow-up are needed. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts HHSN275201200005C, HHSN267200700019C). The sponsor played no role in the study design, data collection, data analysis or interpretation, writing of the manuscript or decision to submit the article for publication. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Impact of parental obesity on neonatal markers of inflammation and immune response.

BACKGROUND/OBJECTIVES: Maternal obesity may influence neonatal and childhood morbidities through increased inflammation and/or altered immune response. Less is known about paternal obesity. We hypothesized that excessive parental weight contributes to elevated inflammation and altered immunoglobulin (Ig) profiles in neonates. SUBJECTS/METHODS: In the Upstate KIDS Study maternal pre-pregnancy body mass index (BMI) was obtained from vital records and paternal BMI from maternal report. Biomarkers were measured from newborn dried blood spots (DBS) among neonates whose parents provided consent. Inflammatory scores were calculated by assigning one point for each of five pro-inflammatory biomarkers above the median and one point for an anti-inflammatory cytokine below the median. Linear regression models and generalized estimating equations were used to estimate mean differences (ß) and 95% confidence intervals (CI) in the inflammatory score and Ig levels by parental overweight/obesity status compared with normal weight. RESULTS: Among 2974 pregnancies, 51% were complicated by excessive maternal weight (BMI>25), 73% by excessive paternal weight and 28% by excessive gestational weight gain. Maternal BMI categories of overweight (BMI 25.0-29.9) and obese class II/III (BMI≥35) were associated with increased neonatal inflammation scores (ß=0.12, 95% CI: 0.02, 0.21; P=0.02 and ß=0.13, CI: -0.002, 0.26; P=0.05, respectively) but no increase was observed in the obese class I group (BMI 30-34.9). Mothers with class I and class II/III obesity had newborns with increased IgM levels (ß=0.11, CI: 0.04, 0.17; P=0.001 and ß=0.12, CI: 0.05, 0.19); P<0.001, respectively). Paternal groups of overweight, obese class I and obese class II/III had decreased neonatal IgM levels (ß=-0.08, CI: -0.13,-0.03, P=0.001; ß=-0.07, CI: -0.13, -0.01, P=0.029 and ß=-0.11, CI:-0.19,-0.04, P=0.003, respectively). CONCLUSIONS: Excessive maternal weight was generally associated with increased inflammation and IgM supporting previous observations of maternal obesity and immune dysregulation in offspring. The role of paternal obesity requires further study.

An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong.

OBJECTIVE: New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong. PARTICIPANTS: Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society. EVIDENCE: A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution. CONSENSUS PROCESS: Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature. CONCLUSIONS: Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

Infertility treatment and children's longitudinal growth between birth and 3 years of age.

STUDY QUESTION: Does early childhood growth from birth through to 3 years of age differ by mode of conception? SUMMARY ANSWER: Findings suggest early childhood growth was comparable for children irrespective of infertility treatment, but twins conceived with ovulation induction with or without intrauterine insemination (OI/IUI) were slightly smaller than twins conceived without treatment. WHAT IS KNOWN ALREADY: Although studies have found that babies conceived with infertility treatment are born lighter and earlier than infants conceived without treatment, little research especially for non-assisted reproductive technology (ART) treatments has focused on their continued growth during early childhood. STUDY DESIGN, SIZE, DURATION: Upstate KIDS recruited infants born (2008-2010) to resident upstate New York mothers. Infants were sampled based on birth certificate indication of infertility treatment; specifically, for every singleton conceived by infertility treatment, three singletons without infertility treatment were recruited and matched on region of birth. All multiple births irrespective of treatment were also recruited. Children were prospectively followed, returning questionnaires every 4-6 months until 3 years of age. In total, 3905 singletons, 1129 sets of multiples (96% of whom were twins) enrolled into the study. Analyses included 3440 (88%) singletons (969 conceived with treatment; specifically, 433 with ART and 535 with OI/IUI) and 991 (88%) sets of multiples (439 conceived with treatment; specifically 233 with ART and 206 with OI/IUI) with growth data available. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mothers reported infertility treatment use at baseline and children's height and weight from pediatric visits. Self-reported use of ART was previously verified by linkage with the US Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. Mixed linear models with cubic splines accounting for age and age-gender interactions were used to estimate mean differences in growth from birth to 3 years by infertility treatment status and adjusting for maternal age, race, education, private insurance, smoking status during pregnancy, maternal pre-pregnancy and paternal body mass indices (BMI). MAIN RESULTS AND THE ROLE OF CHANCE: Compared with singletons conceived without treatment (n = 2471), singletons conceived by infertility treatment (433 by assisted reproductive technologies (ART), 535 by OI/IUI and 1 unknown specific type) did not differ in growth. Compared with twins not conceived with treatment (n = 1076), twins conceived with OI/IUI (n = 368) weighed slightly less over follow-up (122 g). They were also proportionally smaller for their length (-0.17 weight-for-length z-score units). No differences in mean size over the 3 years were observed for twins conceived by ART, though some evidence of rapid weight gain from birth to 4 months (adjusted OR 1.08; 95% CI: 1.00-1.16) suggestive of catch up growth was observed. LIMITATIONS, REASONS FOR CAUTION: Participants from upstate New York may not be representative of US infants. Although accounted for in statistical analysis, attrition during follow-up may have limited power to detect small differences. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to prospectively track the growth of children conceived with and without infertility treatment in the USA, including a substantial number of twins. Our findings are similar to what was previously observed in the ART literature outside of the states. STUDY FUNDING/COMPETING INTERESTS: Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C). Authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Update to the Hong Kong Epilepsy Guideline: evidence-based recommendations for clinical management of women with epilepsy throughout the reproductive cycle.

Since the publication of the Hong Kong Epilepsy Guideline in 2009, there has been significant progress in antiepileptic drug development. New AEDs have emerged, and data about their uses have been published. Women require special attention in epilepsy care. Drug teratogenicity, pregnancy, breastfeeding, contraception, reproduction technology, menopause, and catamenial epilepsy are major topics. Antiepileptic drugs should be chosen individually for patients who are pregnant or may become pregnant with consideration of their teratogenicity and seizure control properties. Folate is commonly prescribed for women of childbearing age who are taking antiepileptic drugs. Spontaneous vaginal delivery and breastfeeding are not contra-indicated in most cases but need to be considered individually based on the patient's medical condition and wishes. Serum drug level monitoring of certain antiepileptic drugs during pregnancy and puerperium can guide dosage adjustment. For catamenial epilepsy, intermittent benzodiazepines such as clobazam during the susceptible phase of the menstrual cycle could be a treatment option.

A 5-week whole body vibration training improves peak torque performance but has no effect on stretch reflex in healthy adults: a randomized controlled trial.

AIM: This study aimed to investigate the neuromuscular adaptation following a 5-week high frequency and low amplitude whole body vibration (WBV) exercise training. METHODS: The study is a prospective, double blind, randomized controlled intervention design with a total of 19 subjects volunteered to participate in the study. They were randomly assigned either to WBV exercise training or control group. Both groups participated in a 5-week training program. The intervention group received WBV in semi-squat position on a device with an amplitude of 0.76 mm, frequency of 40Hz, and peak acceleration of 23.9 m/s2. Each vibration training session consisted of 6 series of 60s on with 30s rest period in between. The control group underwent the same statically mini-squatting position without exposure to WBV. The effectiveness of the vibration program was evaluated by vertical jump test and the isokinetic knee extensor peak torque. The possible neural factors that contributed to the improved muscular performance were evaluated by the stretch induced knee jerk reflex. RESULTS: WBV training significantly enhanced the isokinetic knee extensor peak torque performance. Two-way mixed repeated measures analysis of variance revealed significant time effect of the changes in the peak torque (P=0.043) and the effect was significantly different between the intervention and control group (P=0.042). WBV did not affect vertical jump height, reflex latency of VL, EMGVL, and knee jerk angle. CONCLUSION: The results of this study do not support the hypothesis that the improvement in the muscular performance when subjects exposed to WBV training is attributed by neuromuscular efficiency via modulation of the muscle spindle sensitivity.

Height and the risk of gestational diabetes: variations by race/ethnicity.

AIMS: Gestational diabetes is a common pregnancy complication affecting races/ethnicities disproportionally. Adult height, an indicator of both genetic and early-life factors, is inconsistently associated with gestational diabetes risk. We examined the association and whether it varies by races in a nationally representative US cohort. METHODS: Analyses were conducted among 135 861 pregnancies in the Consortium on Safe Labor, 5567 of which were diagnosed with gestational diabetes based on medical records review. Generalized estimating equations were used to estimate odds ratios (95% confidence intervals) of gestational diabetes, controlling for other risk factors including body weight. Additionally, a meta-analysis of 15 761 pregnancies with gestational diabetes and 205 828 without gestational diabetes was conducted to estimate the pooled mean difference in height between those with gestational diabetes and control subjects. RESULTS: Height was inversely associated with gestational diabetes risk across races/ethnicities, with the strongest association among Asians (P for interaction < 0.01). Comparing extreme quartiles (> 168 vs. < 157 cm), adjusted odds ratios (95% confidence intervals) were 0.18 (0.09-0.36) for Asians/Pacific Islanders, 0.33 (0.29-0.38) for non-Hispanic white women, 0.39 (0.31-0.51) for Hispanics and 0.59 (0.47-0.75) for non-Hispanic black women. Meta-analysis found women with gestational diabetes to be significantly shorter than others. CONCLUSIONS: Taller women are at lower risk of developing gestational diabetes, with the magnitude of association varying significantly across races/ethnicities.

Differences in risk factors for incident and recurrent small-for-gestational-age birthweight: a hospital-based cohort study.

OBJECTIVE: Examine whether small-for-gestational-age (SGA) risk factors differed by prior SGA birth. DESIGN: Hospital-based cohort study. SETTING: Utah, USA. POPULATION: Electronic medical record data from 25,241 women who were nulliparous at study entry with ≥2 subsequent consecutive singleton deliveries (2002-2010). METHODS: Estimated adjusted relative risks (RR) and 95% confidence intervals (95% CI) for the association between second pregnancy characteristics and SGA risk. Tested for risk factor differences between recurrence and incidence (Pdifference). MAIN OUTCOME MEASURES: Second pregnancy incident (n = 1067) and recurrent SGA (n = 484) determined using a population-based reference. RESULTS: SGA complicated 20.3 and 4.5% of deliveries to women with and without a prior SGA birth, respectively. Young maternal age (Pdifference = 0.01) and pregnancy hypertensive diseases (Pdifference = 0.03) were associated with incident but not recurrent SGA. Significant risk factors for incidence and recurrence were smoking (incident RR = 1.64 [95% CI 1.22-2.19]; recurrent RR = 1.59 [95% CI 1.17-2.17]), short stature (incident RR = 1.34 [95% CI 1.16-1.54]; recurrent RR = 1.54 [95% CI 1.31-1.82]), prepregnancy underweight (incident RR = 1.32 [95% CI 1.07-1.64]; recurrent RR = 1.30 [95% CI 1.03-1.64]), and inadequate weight gain (incident RR = 1.41 [95% CI 1.22-1.64]; recurrent RR = 1.33 [95% CI 1.10-1.60]). Race-ethnicity, marital or insurance status, alcohol, diabetes, asthma, thyroid disease, depression, or interpregnancy interval were not associated with incidence or recurrence. CONCLUSION: There was considerable overlap in the risk factors for SGA recurrence and incidence. Recurrence and incidence risk factors included smoking, short stature, underweight, and inadequate weight gain. Maternal age and hypertensive diseases increased the risk for incidence only. Regardless of the SGA definition, some potentially modifiable risk factors for recurrence were identified.

Adiposity and sex hormones across the menstrual cycle: the BioCycle Study.

OBJECTIVE: To investigate the influence of adiposity on patterns of sex hormones across the menstrual cycle among regularly menstruating women. SUBJECTS: The BioCycle Study followed 239 healthy women for 1-2 menstrual cycles, with up to eight visits per cycle timed using fertility monitors. METHODS: Serum estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were measured at each visit. Adiposity was measured by anthropometry and by dual energy X-ray absorptiometry (DXA). Differences in hormonal patterns by adiposity measures were estimated using nonlinear mixed models, which allow for comparisons in overall mean levels, amplitude (i.e., lowest to highest level within each cycle) and shifts in timing of peaks while adjusting for age, race, energy intake and physical activity. RESULTS: Compared with normal weight women (n=154), obese women (body mass index (BMI) 30 kg m(-2), n=25) averaged lower levels of progesterone (-15%, P=0.003), LH (-17%, P=0.01), FSH (-23%, P=0.001) and higher free E2 (+22%, P=0.0001) across the cycle. To lesser magnitudes, overweight women (BMI: 25-30, n=60) also exhibited differences in the same directions for mean levels of free E2, FSH and LH. Obese women experienced greater changes in amplitude of LH (9%, P=0.002) and FSH (8%, P=0.004), but no differences were observed among overweight women. Higher central adiposity by top compared to bottom tertile of trunk-to-leg fat ratio by DXA was associated with lower total E2 (-14%, P=0.005), and FSH (-15%, P=0.001). Peaks in FSH and LH occurred later (∼0.5 day) in the cycle among women with greater central adiposity. CONCLUSION: Greater total and central adiposity were associated with changes in mean hormone levels. The greater amplitudes observed among obese women suggest compensatory mechanisms at work to maintain hormonal homeostasis. Central adiposity may be more important in influencing timing of hormonal peaks than total adiposity.

Bone mineral density and blood metals in premenopausal women.

Exposure to metals, specifically cadmium, lead, and mercury, is widespread and is associated with reduced bone mineral density (BMD) in older populations, but the associations among premenopausal women are unclear. Therefore, we evaluated the relationship between these metals in blood and BMD (whole body, total hip, lumbar spine, and non-dominant wrist) quantified by dual energy X-ray absorptiometry in 248 premenopausal women, aged 18-44. Participants were of normal body mass index (mean BMI 24.1), young (mean age 27.4), 60% were white, 20% non-Hispanic black, 15% Asian, and 6% other race group, and were from the Buffalo, New York region. The median (interquartile range) level of cadmium was 0.30 µg/l (0.19-0.43), of lead was 0.86 µg/dl (0.68-1.20), and of mercury was 1.10 µg/l (0.58-2.00). BMD was treated both as a continuous variable in linear regression and dichotomized at the 10th percentile for logistic regression analyses. Mercury was associated with reduced odds of decreased lumbar spine BMD (0.66, 95% confidence interval: 0.44, 0.99), but overall, metals at environmentally relevant levels of exposure were not associated with reduced BMD in this population of healthy, reproductive-aged women. Further research is needed to determine if the blood levels of cadmium, lead, and mercury in this population are sufficiently low that there is no substantive impact on bone, or if effects on bone can be expected only at older ages.

Examining the validity of the drinking motives questionnaire for identifying reward and relief drinking subgroups in college students.

BACKGROUND: Heavy alcohol use in college is associated with a risk of developing alcohol use disorder. Characterizing variability in individual risk factors for alcohol use could help mitigate risk by informing personalized approaches to prevention. This study examined the validity of a brief measure for identifying reward/relief drinking phenotypes in non-treatment-seeking young adults. METHODS: College students (n = 454) who reported binge drinking completed the Drinking Motives Questionnaire-Revised-Short Form (DMQ-R-SF). Confirmatory factor and latent profile analyses (CFA; LPA) of the DMQ-R-SF were performed to assess structural validity and identify reward/relief drinking subgroups. We compared models measuring reward drinking with the DMQ-R-SF enhancement motives (reward-enhancement) subscale to models measuring reward drinking with enhancement and social motives (reward-enhancement/social). Across models, relief drinking was measured with coping motives. We examined associations between reward/relief drinking subgroups and alcohol and personality variables concurrently and prospectively at a 6-week follow-up. RESULTS: A two-factor reward and relief structure of the DMQ-R-SF was supported. Three latent profiles were identified (low reward/low relief: n = 133, high reward/low relief: n = 249; high reward/high relief: n = 72). Both CFA and LPA models that utilized reward-enhancement/social items indicated a better fit than reward-enhancement items alone. At baseline, individuals in the high-reward/high-relief profile demonstrated the poorest alcohol use outcomes and higher negative affect. Those in the high-reward/low-relief profile demonstrated greater alcohol use severity than those in the low-reward/low-relief profile. Prospectively, individuals classified in the high-reward/low-relief subgroup reported greater binge drinking frequency and those in the high-reward/high-relief profile reported greater alcohol consequences. CONCLUSIONS: The DMQ-R-SF is a valid measure for identifying reward and relief drinking subgroups in college students with binge drinking and could have utility for precision prevention efforts that target individuals in the high-reward/low-relief and high-reward/high-relief subgroups.

Hyperfractionated Cyclophosphamide and Dexamethasone Alone or in Combination with Daratumumab and/or Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma: A Single-Center Retrospective Analysis.

BACKGROUND: Hyperfractionated cyclophosphamide and dexamethasone (HyperCd) alone, or with carfilzomib(K) and/or daratumumab(D), represents a potential treatment option when rapid disease control is needed for patients with aggressive presentations of relapsed/refractory multiple myeloma (RRMM). PATIENTS AND METHODS: This is a single-center, retrospective analysis of adult patients with RRMM who received HyperCd with or without K and/or D between May 1, 2016 and August 1, 2019 at the University of Texas MD Anderson Cancer Center. We here report treatment response and safety outcomes. RESULTS: Data from 97 patients, 12 with plasma cell leukemia (PCL), were reviewed in this analysis. Patients had had a median of 5 prior lines of therapy and received a median of 1 consecutive cycle of hyperCd-based therapy. The overall response rate (ORR) of all patients was 71.8% (HyperCd 75%, HyperCdK 64.3%, D-HyperCd 73.3%, and D-HyperCdK 76.9%). Median progression-free survival and overall survival among all patients was 4.3 months (HyperCd 3.1 months, HyperCdK 4.5 months, D-HyperCd 3.3 months, and D-HyperCdK 6 months) and 9.0 months (HyperCd 7.4 months, HyperCdK 9.0 months, D-HyperCd 7.5 months, and D-HyperCdK 15.2 months), respectively. Grade 3/4 hematologic toxicities were common, thrombocytopenia being the most frequent at 76%. Notably, 29-41% of patients per treatment group had existing grade 3/4 cytopenias at initiation of hyperCd-based therapy. CONCLUSION: HyperCd-based regimens provided rapid disease control among MM patients, even when heavily pre-treated and with few remaining treatment options. Grade 3/4 hematologic toxicities were frequent, but manageable with aggressive supportive care.

Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson's disease patients.

OBJECTIVE: The 10 year outcomes and impact of motor and non-motor features on survival of a cohort of new onset Chinese Parkinson's disease (PD) patients were prospectively studied. METHOD: A cohort of new onset PD patients from 1995 to 2002 was recruited from a regional hospital based movement disorder clinic. Subjects were classified into postural instability gait disorder (PIGD), tremor predominant type or mixed subtypes at presentation. All were evaluated yearly for development of sensory complaints, first significant fall, hallucinations, dementia, postural hypotension, speech disturbances, dysphagia and postural instability persisted during 'on' medication state (PIPon). Mortality and predictors of death were determined. RESULTS: 171 new onset PD patients were recruited. After a mean follow-up of 11.3±2.6 years, 50 (29%) patients died. The standardised mortality ratio was 1.1 (CI 0.8 to 1.5, p=0.34). 83 (49%) developed dementia, 81 (47%) had psychosis and 103 (60%) had sensory complaints. Postural hypotension was found in 58 (34%) patients, 108 (63%) had PIPon, 101 (59%) had falls, 102 (60%) had dysphagia, 148 (87%) had freezing of gait and 117 (68%) had speech disturbances. 46 (27%) were institutionalised whereas 54 (32%) lived independently. Dementia (HR 5.0, 95% CI 2.1 to 13.0), PIPon (HR 2.8, 95% CI 1.2 to 6.8), older onset (HR 1.05, 1 year increase in age, 95% CI 1.0 to 1.1) and PIGD type (HR 2.1, 95% CI 1.2 to 3.7) were independent predictors of death. CONCLUSIONS: 10 years into PD, a significant proportion of patients developed dopa resistant motor and non-motor features. Older onset, PIGD type, PIPon and dementia had a negative impact on survival. Standardised mortality ratio was 1.1.

Placental characteristics and risks of maternal mortality 50 years after delivery.

INTRODUCTION: Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as a risk factor for future CVD mortality in mothers. METHODS: Longitudinal study of 33,336 women from the Collaborative Perinatal Project (CPP; 1959-1966) linked to mortality information through December 2016. Pathologists took extensive morphological and histopathological measures. Apart from assessing associations with morphological features, we derived an overall composite score and specific inflammation-related, hemorrhage-related, and hypoxia-related pathologic placenta index scores. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality adjusting for covariates. RESULTS: Thirty-nine percent of women died with mean (standard deviation, SD) time to death of 39 (12) years. Mean (SD) placental weight and birthweight were 436 g (98) and 3156 g (566), respectively. Placenta-to-birthweight ratio was associated with all-cause mortality (adjusted HR 1.03: 1.01, 1.05 per SD in ratio). In cause-specific analyses, it was significantly associated with respiratory (HR 1.06), dementia (HR: 1.10) and liver (HR 1.04) related deaths. CVD, cancer, diabetes and kidney related deaths also tended to increase, whereas infection related deaths did not (HR 0.94; 0.83, 1.06). Placental measures of thickness, diameters, and histopathological measures grouped by inflammatory, hemorrhagic, or hypoxic etiology were not associated with mortality. DISCUSSION: Placental weight in relation to birthweight was associated with long-term maternal mortality but other histopathologic or morphologic features were not.

Influence of eicosapentaenoic acid supplementation on lean body mass in cancer cachexia.

Cancer cachexia is characterised by a progressive loss of muscle, resulting in functional impairment and shorter survival. Eicosapentaenoic acid, an n-3 polyunsaturated fatty acid found in fish, has been studied for its role as an anti-cachexia therapy. Initial results of eicosapentaenoic supplementation in advanced cancer were promising with improvements in lean body mass (LBM), appetite and quality of life. However, subsequent larger phase III clinical trials reported minimal benefits of supplementation. Recently, several studies have used different study designs, which may provide insight on the effectiveness of eicosapentaenoic in cancer cachexia and also on potential sources of divergent results in previous trials. This review examines the potential benefit of eicosapentaenoic supplementation on LBM and discusses limitations with current studies to identify methods which may aid in progressing the research of future clinical trials.

Real-time screening tool for identifying post-traumatic stress disorder in facial trauma patients in a UK maxillofacial trauma clinic.

Post-traumatic stress disorder (PTSD) is a distressing consequence of a traumatic event associated with an increased suicide risk and reduced quality of life. Surgeons often have low confidence in identifying psychological problems. The prevalence of PTSD following facial trauma ranges from 23% to 41%. This highlights the importance of identifying and managing at-risk patients to optimize both mental and physical recovery. IMPARTS (Integrating Mental and Physical healthcare: Research, Training and Services) provides electronic screening tools to guide the non-mental health clinician in the 'real-time' identification, documentation, and management of potential mental health problems. The bespoke IMPARTS facial trauma screening tool was piloted in a UK oral and maxillofacial surgery trauma clinic from July 2015 to November 2017. A total of 199 patients completed screening, with 48 (24%) screening positive for possible PTSD. Further analysis of these 48 patients revealed that four (8%) had PTSD symptoms alone; three (6%) also screened positive for depression, 17 (35%) for co-existing symptoms of anxiety, and 24 (50%) for PTSD, anxiety, and depression. IMPARTS was found to be a highly effective tool aiding the non-mental health clinician to screen for PTSD and initiate prompt management. The data captured informs planning of the psychological support service.

Systematic review and meta-analysis of tracheostomy outcomes in COVID-19 patients.

A systematic review and meta-analysis of the entire COVID-19 Tracheostomy cohort was conducted to determine the cumulative incidence of complications, mortality, time to decannulation and ventilatory weaning. Outcomes of surgical versus percutaneous and outcomes relative to tracheostomy timing were also analysed. Studies reporting outcome data on patients with COVID-19 undergoing tracheostomy were identified and screened by 2 independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Outcome data were analysed using a random-effects model. From 1016 unique studies, 39 articles reporting outcomes for a total of 3929 patients were included for meta-analysis. Weighted mean follow-up time was 42.03±26 days post-tracheostomy. Meta-analysis showed that 61.2% of patients were weaned from mechanical ventilation [95%CI 52.6%-69.5%], 44.2% of patients were decannulated [95%CI 33.96%-54.67%], and cumulative mortality was found to be 19.23% [95%CI 15.2%-23.6%] across the entire tracheostomy cohort. The cumulative incidence of complications was 14.24% [95%CI 9.6%-19.6%], with bleeding accounting for 52% of all complications. No difference was found in incidence of mortality (RR1.96; p=0.34), decannulation (RR1.35, p=0.27), complications (RR0.75, p=0.09) and time to decannulation (SMD 0.46, p=0.68) between percutaneous and surgical tracheostomy. Moreover, no difference was found in mortality (RR1.57, p=0.43) between early and late tracheostomy, and timing of tracheostomy did not predict time to decannulation. Ten confirmed nosocomial staff infections were reported from 1398 tracheostomies. This study provides an overview of outcomes of tracheostomy in COVID-19 patients, and contributes to our understanding of tracheostomy decisions in this patient cohort.