In a retrospective study, prior miscarriage, serum albumin, high hematocrit, creatinine and uric acid were associated with an increased likelihood of progression from gestational hyperte[r]
hormone involved in breast milk production) are all suggested factors in its development.(Hilfiker- Kleiner et al., 2015; Ware et al., 2016) Many women with peripartum cardiomyopathy regain cardiac function: one study found that at one year post-delivery, 60% showed full recovery and 31% showed partial recovery.(Abou Moulig et al., 2018) Maternal and fetal outcomes are generally positive during future pregnancies.(Codsi et al., 2018) That said, about one-third of women who have had peripartum cardiomyopathy experience relapse in subsequent pregnancies.(Elkayam, 2014) At two years postpartum, maternal mortality ranges from 0% to 9%, with higher rates seen in women of African descent.(Sliwa et al., 2018) Outcomes are generally better when the level of maternal heart failure at time of diagnosis is classified as class I or II (little or no impact on physical activity) rather than class III or IV (marked or severe impact) per the New York Heart Association (NYHA) Functional Classification system.(American Heart Association (AHA), 2017; Sliwa et al., 2006) For details about this system, visit http://bit.ly/30Gy1cp.
increase in metabolic syndrome development at the age of 22 when compared with individuals born with appro- priate weight forgestational age (AGA). 21
Tothe best of our knowledge, there are no data available comparing metabolic outcomes of obese adults born SGA with obese adults born AGA nor on therisk of a metabolic- ally unhealthy phenotype in the obese SGA population. We hypothesise that since SGA individuals tend to exhibit more unfavourable metabolic outcomes in adulthood, they would also not bene fit from a MHO phenotype in case of obesity. On the other hand, obese AGA individuals would have a higher favourable risk of evolution towards MHO in comparison to their SGA counterparts. The objective of this study was to assess therisk of MUHO in obese SGA versus AGA individuals in the French Haguenau cohort. One of the most important interests of the Haguenau cohort is that the recruited participants are young adults who have completed body development. Studying a group of young obese adults could avoid the presence of con- founding metabolic or non-metabolic factors that would be present in the case of obesity at an older age.
BP, although the effect was less marked than with GLP-1 receptor agonists (exenatide, liraglutide) 63-65 . In most phase 2-3 trials with DPP-4 inhibitors, no consistent effect on BP (systolic BP : −0.1; 95% CI −1.2 to +0.8 mmHg) has been recorded 66 . However, none of these trials was designed to specifically evaluate the effects on BP, which was measured routinely, as part of the safety assessment, and in T2DM patients not specifically selected forhypertension 66 . Nevertheless, sitagliptin has some more specific data. It produced small but statistically significant reductions of 2-3 mmHg in 24-hour ambulatory BP measurements in nondiabetic patients with mild to moderate hypertension 64 . Sitagliptin also lowered systolic BP without reducing body mass index, independent of the blood glucose reduction, in Japanese hypertensive patients with T2DM 67 . Recent experimental data suggested that the local actions of incretins may be via their key role in regulating natriuresis, thereby lowering BP, especially in individuals with salt-sensitive hypertension 68 .
2
Abstract
Understanding the developmental course of all health issues associated with preterm birth is important from an individual, clinical and public health point-of-view. Both the number of preterm births and proportion of survivors have increased steadily in recent years. The UK Millennium Cohort Study (n=18 818) was used to examine the association of gestational age with maternal ratings of general health and behavior problems at ages 5 and 11 years using binary and multinomial logistic regression analyses. The association between mothers’ ratings of general health and behavior problems was relatively weak at each time point. Children rated as being in poor general health remained constant over time (4.0% at age 5, 3.8% at age 11), but children rated as having behavioral problems increased by almost 100% (5.6% at 5; 10.5% at 11). A gradient of increasing risk with decreasing gestational age was observed for a composite health measure (general health problems and/or behavior problems) at age 5, amplified at age 11 and was strongest for those with chronic problems (poor health at both age 5 and age 11). This association was found to be compounded by child sex, maternal characteristics at birth (education, employment, marital status) and duration of breast feeding. Integrated support to at-risk families initiated during, or soon after pregnancy, may prevent chronic problems and might potentially reduce long term health costs for both the individual and health services.
2.3. Assessment of Lifestyle Factors 2.3.1. Dietary Intake Assessment
At inclusion, participants completed three 24-h dietary records (24 HR) randomly allocated over a two-week period, including two weekdays and one weekend day; this collection method has shown high agreement with the reference method (interview with a dietician) [ 12 ] and was validated against biomarkers [ 13 , 14 ]. Participants reported all foods and beverages consumed at each meal. The NutriNet-Santé food composition table, which includes more than 3000 food items, enabled to estimate nutrient intakes [ 15 ]. Portion sizes were either estimated with photographs, derived from a validated picture booklet [ 16 ], or quantity consumed was directly entered. Daily dietary intakes were calculated as the weighted average fromthe three 24 HR. A frequency questionnaire on the amount and type of alcohol consumed was used to calculate alcohol intake (g ethanol/day). Based on these nutritional data, we have computed a DASH-Style Diet score as previously developed by Fung et al. [ 17 ]; including 8 dietary components whose consumption should be increased (fruits, vegetables, nuts and legumes, low-fat dairy, whole grains) or minimized (sodium, sweetened beverages, red and processed meats). Gender–specific (ranging from 1 to 5) quintiles were used for individual’s sub scores in each dietary component. Thus, final DASH score ranging (8 to 40 points) was calculated by adding all the sub scores.
Experimental set-up. Figure 1 illustrates the experimental design. The four experimental groups were two control groups (wt females mated to wt males and injected with buffer during pregnancy (Ctrl-buff) and wt females mated to wt males and injected with rA1M during pregnancy (Ctrl -A1M)), and two preeclampsia groups (wt females mated to transgenic males and injected with buffer during pregnancy (PE-buff) and wt females mated to transgenic males and injected with rA1M during pregnancy (PE-A1M)). The females used were 10–20 weeks old. The experiment lasted from time of mating until termination at gestation day 17.5 dpc. The females were given six i.p. injections of either buffer or rA1M every second day starting at 6.5 dpc. BP (systolic and dias- tolic) was measured every second day, starting before mating to get a baseline and throughout the experiment (for ~35 consecutive days per mouse), by a non-invasive tail-cuff device (CODA8 with four channels, EMKA Technologies). Non-anesthetized mice, previously trained for 1 week tothe manipulation, were placed in animal restrainers of appropriate size and placed on a warming platform. The system uses volume pressure recording sen- sors and an occlusion tail-cuff to repeatedly determine changes in the tail volume, corresponding to systolic and diastolic pressure, with at least 3 satisfactory measurements per day. Systolic and diastolic BP always displayed similar curve profiles in all groups analysed, therefore only systolic BP is shown. Urine was collected during the experiment non-invasively by putting female mice on a cold metal surface to induce urination, and stored at −80 °C until use. However, urine samples were difficult to collect from all females at every time point, and therefore results were pooled within each group for each gestational period (early, mid and late). Whole blood was collected fromthe Saphena vein at early- and mid-gestation, and fromthe Cava vein at time of termination in Li-Heparin tubes. Plasma was separated from whole blood and then stored at −80 °C until use. Females were sac- rificed at day 17.5 dpc and organs collected. The organs were dissected and biopsies were fresh-frozen on dry ice, paraffin-embedded, or fixed for TEM. Pups were euthanized, counted, and weighed. The placentas and maternal hearts were weighed. Differences in number of animals per group are related to different experimental locations; Paris, France and Lund, Sweden (Supplementary Table S2). The following data analysis were performed on mouse experiments executed in Paris: BP measurements, Nitrotyrosine analysis, hA1M-RIA analysis, qPCR analysis, and plasma sEng/sFlt1 analysis. The following data analysis were performed on mouse experiments executed in Lund: Hypoxyprobe analysis, HE/Masson/TEM microscopy analysis, ACR analysis and MRI analysis. Heart weight was included from both locations, explaining the higher n-numbers.
Ethical approval forthe Whitehall II study was obtained fromthe University College London Medical School committee on the ethics of human research; all participants provided written informed consent.
Assessment of RiskFactors and Prevalent Disease
We measured systolic blood pressure and diastolic blood pressure twice in the sitting position after 5 minutes rest with the Hawksley random-zero sphygmomanometer (Phases 1 to 5) and OMRON HEM 907 (Phase 7). The average of the two readings was taken to be the measured systolic and diastolic blood pressure. Prehypertension was defined as systolic blood pressure from 120 to 139 mm Hg or diastolic blood pressure from 80 to 89 mm Hg. Current smoking and parental hypertension were self-reported. Weight was measured in underwear tothe nearest 0.1 kg on Soehnle electronic scales. Height was measured in bare feet tothe nearest 1 mm using a stadiometer with the participant standing erect with head in the Frankfort plane. Body mass index (BMI) was calculated as weight (kilograms)/height (meters) squared.
Advantages and disadvantages of survival analysis with time-dependent covariates have been discussed in the literature.(312) One of main advantages of time-dependent covariates is that you can incorporate important events that occur during the study period. The main disadvantages include over-adjustment and decreased usefulness for clinicians. With time-dependent covariates, "effect- cause" may be a problem by including factors that are proximal to outcomes than baseline exposure measurements. One way to deal with this problem is to "lag" the time-dependent measurements substantially before the outcome but still after the baseline. In our study, all participants are pregnant women, with relatively short and approximately constant follow up time (from trial entry to delivery). Furthermore, unlike chronic disease such as cancer for which the incidence tends to rise over time, it may be inappropriate to apply cox regression model in modelling PE as an outcome since the assumption of increasing risk over time does not hold– typical PE cases tend to occur earlier.
II.3.6 Other Variables
During baseline home visit of the 3C study (1999-2001), all participants underwent a face-to- face interview using a standardized questionnaire, administered by a trained psychologist or nurse forthe assessment of systemic riskfactors. A systemic clinical examination included two measures of systolic and diastolic blood pressure using a digital electronic tensiometer (OMRON M4; Omron Santé France SAS, Rosny-sous-Bois, France) and anthropometric measurements. The first blood pressure measurement was recorded at the beginning of the interview and the second one at the end. The average systolic blood pressure (SBP) was the average of these two SBP measures. The same calculation was made forthe average diastolic blood pressure (DBP). Hypertension was defined as average SBP≥140 mmHg and/or average DBP≥90 mmHg and/or antihypertensive medication use at baseline examination. The Body Mass Index (BMI; kg/m2) was calculated as the weight in kilograms divided by the height in square meters. Diabetes was defined as medication use and/or self-reported diabetes. For participants who were current or past smokers, the number of pack-years was calculated as: (number of smoking years) × (mean number of cigarettes per day) ⁄ 20. Hypercholesterolemia was defined by hypercholesterolemia medication. Past medical history including ophthalmic laser treatment or cataract surgery was recorded. Cataract extraction was checked during slip lamp examination.
Results
The number of women who agreed to participate in our large prospective study was very high, with a recruitment rate of 86%. Of the 7866 participants of the prospective study, 6878 pregnant women met our inclusion criteria, of whom 335 (4.9%) were exposed to antidepressants and/or anxiolytic drugs at some point during pregnancy and 218 of them were exposed before the 16th week of pregnancy (Fig. 1 ). Among these 218 women, 167 continued using antidepressant and/or anxiolytic medi- cation for at least another trimester (149/167 were still users in the third trimester). Forty-one women had a non-medicated depression or anxiety during the preg- nancy. Among the 6878 pregnant women, 202 (2.94%) and 127 (1.85%) women developed GH and PE respect- ively. These rates are similar to those observed in the Quebec City area in another independent study [ 36 ]. Since PE pathophysiological modifications begin during the first trimester, we studied these 218 antidepressant/ anxiolytic users who began medication before the 16th week and compared them to women unexposed to anti- depressant/anxiolytic medication, depression and anxiety forthe detailed analysis (Fig. 1 ). By limiting the present study to exposure before the 16th week, we wanted to ensure that antidepressant/anxiolytic exposure during the pregnancy began before the HDP diagnosis. A total of 6761 pregnancies (6474 women) were studied. Of note, none of the women contributing more than once in the cohort are found in the subgroup exposed to anti- depressant/anxiolytic and who developed HDP.
tracheostomy, blood transfusion, and comorbidities such as diabetes and associated liver disease. 7,8 Finally, the type of pharyngeal suture has also been implicated. 9
Surgery has been marked in recent years by the emergence of early rehabilitation programs. Initially performed as part of colorectal carcinologic surgery, they have been extended to other surgical specialties. 10 In 2016, the French HAS published an improved recovery program after surgery, the objectives of which are to increase patient satisfaction, reduce therisk of post-op complications, and reduce the length of hospital stay. 11 Several studies have examined theriskfactorsfor salivary fistula, the incidence of which remains high. We studied these riskfactors in a cohort of patients and established a risk score for pharyngocutaneous fistula after TL or TPL. The objective was to be able to use this preoperative risk score to modify practices and thus reduce the incidence of salivary fistula.
Riskfactors were classified as pre-, peri-, or postopera- tive (Table 1). Preoperative riskfactors were those relating tothe patient and their cancer. Patient-related factors included age, performance index (World Health Organiza- tion [WHO] score), diabetes, liver disease, gastroesophageal reflux disease, smoking over 20 pack-years (PY) active, alcoholism defined by more than 3 glasses of alcohol per day, and undernutrition. Preoperative hemoglobinemia and albuminemia as well as the presence or absence of preo- perative re-nutrition were also taken into account. Cancer- related factors included a history of radiotherapy, chemotherapy, or concomitant radiochemotherapy, a history of cervical surgery, size, and tumor stage (as classified by the TNM 7 UICC 2009 classification) and the need for a preoperative tracheotomy.
particularly disadvantaged and at-risk student population, especially in urban settings (Milner, 1994). This is quite problematic in light of results from empirical studies that have shown that classmates’ socioeconomic status influences student achievement more than their own status does (Caldas & Bankston, 1997). We suggest that contagion of potentially harmful social norms among public school students who may have lower academic ambitions than their peers from a wealthier, more educated background could be one of the mechanisms explaining such findings. Decision makers should therefore be aware that political choices that influence the composition of student populations in various schools can create gaps in the quality of the learning environment offered to students from lower versus middle to higher social classes. The resulting disparity in academic gains made by students fromthe two systems is probably not entirely due to differences in financial or human resources in the schools—it is likely influenced by lack of access to positive peer influences in public schools.
al., 2016). In keeping with these studies, we found the association between anxiety and both short-
term and long-term RCE to be robust tothe effect of cardiac disease severity. We adjusted for severity in our study using diagnosis at registry entry and chest pain as proxies.
In addition, we found the anxiety but not the agitation subscale to be associated with an increased RCE risk. The agitation subscale can be considered less ‘anxiety-specific’ than the anxiety subscale. Indeed it focuses on restlessness, tenseness and difficulties in relaxing whilst the anxiety items capture fear and panic responses related to physical hyperarousal of anxiety. Intuitively, feeling ‘wound-up’ could be thought of as risk inducing, especially as relaxation therapy is a common feature of secondary CVD prevention programmes (Whalley, Thompson and Taylor, 2014). However, these symptoms alone distinguished fromthe other more anxiety-specific ones may not be sufficient, nor meet alone plausibility criteria forthe pathophysiological processes linking anxiety to cardiac events. Tothe best of our knowledge, only one other study has looked at the different subtypes of anxiety and no other has used any of the HADS three-factor structures. Roest et al (2014) examined the Hamilton Anxiety and Depression Rating Scale symptom dimensions in 418 patients in relation to recurrent MI and all-cause mortality (Roest et al., 2014). Associations were significant for somatic anxiety, but a trend only was found for psychological anxiety. Comparison with the HADS is limited due tothe partial overlap of items covered by the different scales. For instance, there are no
Riskfactorsfor skin infections in Mycosis Fungoides
E. Lebas 1 MD, J.E. Arrese 2 MD, PhD, A.F. Nikkels 1 MD, PhD
Departments of 1 Dermatology and 2 Dermatopathology, Liège University Hospital CHU, 4000 Liège, Belgium
Introduction and objectives Mycosis fungoides (MF) is the most frequent type of primary cutaneous natural killer cell and T-cell lymphoma. One of the major complications of MF is infection, in particular cutaneous infections. Our purpose was to assess the number of skin infections, their clinical characteristics, the diagnostic methods and the therapeutic management to identify riskfactorsfor skin infection in MF patients.
About gestational diabetes is a metabolic abnormalities occurring during pregnancy associated with carbohydrate metabolism (Butte, 2000). Decreased maternal pregravid insulin sensitivity (insulin resistance) coupled with an inadequate insulin response are the pathophysiological mechanisms underlying the development of gestational diabetes (Catalano et al 2003). Caractised by altering of levels and function of insulin receptors , control of insulin-dependent processes in the human placenta will change from mother to foetus throughout gestation particular interest in conditions associated with altered maternal or foetal insulin levels (Hiden et al., 2006).Gestational diabetes mellitus is a disease that associates with endoplasmic reticulum stress (ERS) (Hong et al., 2016),it plays a role in the pathogenesis of diabetes, contributing to pancreatic beta-cell loss and insulin resistance (Eizirik et al., 2008). Increased phosphorylation of inositol-requiring enzyme 1α (P-IRE-1α) resulting in higher c-Jun N-terminal kinase (JNK) activity causes phosphorylation of insulin receptor substrate 1 at serine307(P-Ser-IRS-1) ending in lower insulin receptor (IR)-associated cell signaling in response to insulin , thus inhibiting insulin signaling pathway, a condition that turns into a stage of insulin resistance due to defective downstream signaling, including reduced protein kinase P/Akt activation and NO synthesis (Sobrevia et al., 2016).
A recent review of cancer risks in primary aluminum production workers observed that while there have been several reports of increased risks of pancreatic cancer in this industry, there is currently insufficient evidence to indicate a relationship with a specific exposure in aluminum reduction potrooms (51). A likely candidate for such an effect among worker cohorts in aluminum production is PAHs, because these compounds are established carcinogens for other tumour sites, most notably the lung and bladder (44, 45). We therefore tested this hypothesis in the MMC study population but did not observe an increase in risk of pancreatic cancer with exposure to PAHs from any source. This finding is in agreement with some other studies which considered the same research question (26, 55). However, these studies mainly examined PAHs derived from diesel exhaust. In fact, PAHs form a large group of hundreds of different compounds and the profile of PAHs to which one is exposed depends on the source material (98). In aluminum reduction potrooms, PAHs are primarily derived fromthe coal tar used in the production process (51). The compounds emitted fromthe heating and combustion of this material may contain the putative pancreatic carcinogens. Such a hypothesis would be supported by the finding of an increased risk of pancreatic cancer with exposure to coal combustion products in our analysis. The latter exposure includes a mixture of particulates (carbon, silica, alumina, and iron oxides) and gases (aldehydes, carbon monoxide, nitrogen oxides, sulfur oxides and hydrocarbons) (98). Furthermore, we found twofold excess risks of pancreatic cancer among those substantially exposed to soot, a black substance formed by the combustion of carbon compounds including coal.
Additional factors linked to acquisition of meningo- cocci over the course of this study were smoking tobacco and exposure to wood smoke. Smoking, pas- sive exposure to smoke and to smokers has been shown to convey a high risk of carriage and invasive disease in high-income countries [18–21]. Exposure to cigarette smoke has also been linked totherisk of car- riage in the meningitis belt [7, 14]. The higher risk of acquisition from smoke exposure in this study suggests a direct riskfrom smoke itself, potentially from inter- ference with mucosal immunity, as exposure to wood smoke was an independent risk factor. Exposure to smoke from wood fires has also been shown as a risk factor for meningococcal meningitis in northern Ghana [22]. Although use of wood as primary cooking fuel was not found to be a significant risk factor, this could be explained by the fact that nearly all study partici- pants relied on wood as primary fuel or that some households used outdoor kitchens, thus moderating the degree of exposure.
It is commonly stated that the type of surgery influ- ences therisk of PONV. 1–3,6 Our data reflected a casual impact of surgical procedures on nausea alone, notably gynecology, and abdominal surgery with the exception of urology that increased both nausea and vomiting. These results are in contradiction with the papers from Apfel et al. 16,24 and other authors 8,22,31 who found that the type of surgery did not seem to play a major role in the incidence of PONV. Studies published to date have used a variety of methodologies that do not permit mean- ingful conclusions to be drawn. To our knowledge, this is the first that accounts forthe high association between the two outcomes. In that respect, the bivariate Dale model is an interesting alternative to classic approaches, which apply logistic regression to each outcome sepa- rately and hence ignore the dependence structure of nausea and vomiting.