UNASSIGNED: The risk factors of cardiovascular disease (CVD) in end-stage renal disease (ESRD) with hemodialysis remain not fully understood. In this study, we developed and validated a clinical-longitudinal model for predicting CVD in patients with hemodialysis, and employed Mendelian randomization to evaluate the causal 6study included 468 hemodialysis patients, and biochemical parameters were evaluated every three months. A generalized linear mixed (GLM) predictive model was applied to longitudinal clinical data. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the performance of the model. Kaplan-Meier curves were applied to verify the effect of selected risk factors on the probability of CVD. Genome-wide association study (GWAS) data for CVD (n = 218,792,101,866 cases), end-stage renal disease (ESRD, n = 16,405, 326 cases), diabetes (n = 202,046, 9,889 cases), creatinine (n = 7,810), and uric acid (UA, n = 109,029) were obtained from the large-open GWAS project. The inverse-variance weighted MR was used as the main analysis to estimate the causal associations, and several sensitivity analyses were performed to assess pleiotropy and exclude variants with potential pleiotropic effects.
UNASSIGNED: The AUCs of the GLM model was 0.93 (with accuracy rates of 93.9% and 93.1% for the training set and validation set, sensitivity of 0.95 and 0.94, specificity of 0.87 and 0.86). The final clinical-longitudinal model consisted of 5 risk factors, including age, diabetes, ipth, creatinine, and UA. Furthermore, the predicted CVD response also allowed for significant (p < 0.05) discrimination between the Kaplan-Meier curves of each age, diabetes, ipth, and creatinine subclassification. MR analysis indicated that diabetes had a causal role in risk of CVD (β = 0.088, p < 0.0001) and ESRD (β = 0.26, p = 0.007). In turn, ESRD was found to have a causal role in risk of diabetes (β = 0.027, p = 0.013). Additionally, creatinine exhibited a causal role in the risk of ESRD (β = 4.42, p = 0.01).
UNASSIGNED: The results showed that old age, diabetes, and low level of ipth, creatinine, and UA were important risk factors for CVD in hemodialysis patients, and diabetes played an important bridging role in the link between ESRD and CVD.

UNASSIGNED: Postpartum depression (PPD) is a type of depressive episode related to parents after childbirth, which causes a variety of symptoms not only for parents but also affects the development of children. The causal relationship between potential risk factors and PPD remains comprehensively elucidated.
UNASSIGNED: Linkage disequilibrium score regression (LDSC) analysis was conducted to screen the heritability of each instrumental variant (IV) and to calculate the genetic correlations between effective causal factors and PPD. To search for the causal effect of multiple potential risk factors on the incidence of PPD, random effects of the inverse variance weighted (IVW) method were applied. Sensitivity analyses, including weighted median, MR-Egger regression, Cochrane\'s Q test, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), were performed to detect potential Mendelian randomization (MR) assumption violations. Multivariable MR (MVMR) was conducted to control potential multicollinearity.
UNASSIGNED: A total of 40 potential risk factors were investigated in this study. LDSC regression analysis reported a significant genetic correlation of potential traits with PPD. MR analysis showed that higher body mass index (BMI) (Benjamini and Hochberg (BH) corrected p = 0.05), major depression (MD) (BH corrected p = 5.04E-19), and schizophrenia (SCZ) (BH corrected p = 1.64E-05) were associated with the increased risk of PPD, whereas increased age at first birth (BH corrected p = 2.11E-04), older age at first sexual intercourse (BH corrected p = 3.02E-15), increased average total household income before tax (BH corrected p = 4.57E-02), and increased years of schooling (BH corrected p = 1.47E-11) led to a decreased probability of PPD. MVMR analysis suggested that MD (p = 3.25E-08) and older age at first birth (p = 8.18E-04) were still associated with an increased risk of PPD.
UNASSIGNED: In our MR study, we found multiple risk factors, including MD and younger age at first birth, to be deleterious causal risk factors for PPD.

OBJECTIVE: To determine the impact implementation of Emergency Department Clinical Emergency Response System (EDCERS) on inpatient deterioration events and identify contributing causal factors.
METHODS: EDCERS was implemented in an Australian regional hospital, integrating a single parameter track and trigger criteria for escalation of care, and emergency, specialty and critical care clinician response to patient deterioration. In this controlled pre-post study, electronic medical records of patients who experienced a deterioration event (rapid response call, cardiac arrest or unplanned intensive care admission) on the ward within 72 h of admission from the emergency department (ED) were reviewed. Causal factors contributing to the deteriorating event were assessed using a validated human factors framework.
RESULTS: Implementation of EDCERS reduced the number of inpatient deterioration events within 72 h of emergency admission with failure or delayed response to ED patient deterioration as a causal factor. There was no change in the overall rate of inpatient deterioration events.
CONCLUSIONS: This study supports wider implementation of rapid response systems in the ED to improve management of deteriorating patients. Tailored implementation strategies should be used to achieve successful and sustainable uptake of ED rapid response systems and improve outcomes in deteriorating patients.

The UK Medical Certificate of Stillbirth (MCS) records information relevant to the cause of stillbirth of infants ≥24 weeks\' gestation. A cross-sectional audit demonstrated widespread inaccuracies in MCS completion in 2009 in North West England. A repeat study was conducted to assess whether practice had improved following introduction of a regional care pathway.
266 MCS issued in 14 North West England obstetric units during 2015 were studied retrospectively. Cause of death was assigned following review of information available at the time of MCS completion. This was compared to that documented on the MCS, and to data from 2009.
Twenty-three certificates were excluded (20 inadequate data, 3 late miscarriages). 118/243 (49%) MCS contained major errors. Agreement between the MCS and adjudicated cause of stillbirth was fair (Kappa 0.31; 95% CI 0.24, 0.38) and unchanged from 2009 (0.29). In 2015, excluding 34 terminations of pregnancy, the proportion of MCSs documenting \"unexplained\" stillbirths (113/211; 54%) was reduced compared to 2009 (158/213; 74%); causality could be assigned after case note review in 78% cases. Recognition of fetal growth restriction (FGR) as a cause of stillbirth improved (2015: 30/211; 14% vs 2009: 1/213; 0.5%), although 71% cases were missed. 47% MCSs following termination of pregnancy documented an iatrogenic primary cause of death.
Completion of MCSs remains inaccurate, particularly in recognition of FGR as a cause of stillbirth. Detailed case note review before issuing the MCS could dramatically improve the usefulness of included information; evaluation of practitioner education programmes/internal feedback systems are recommended.

What are the primary causes of severe male factor infertility?
Although 40% of all patients showed primary causes of infertility, which could be subdivided into three groups based on the severity of their effect, ~75% of oligozoospermia cases remained idiopathic.
There are few large-scale epidemiological studies analyzing the causes of male factor infertility.
A prospective clinical-epidemiological study was conducted at the Andrology Centre, Tartu University Hospital between 2005 and 2013, recruiting male partners of couples failing to conceive a child for over ≥12 months. Among 8518 patients, 1737 (20.4%) were diagnosed with severe male factor infertility. A reference group of fertile controls was comprised of 325 partners of pregnant women.
The mean age of infertility patients and fertile controls was 33.2 ± 7.3 and 31.7 ± 6.3 years, respectively. All participants were examined using a standardized andrology workup, accompanied by a structured medical interview. Hormonal analysis included serum FSH, LH and testosterone. Semen quality was determined in accordance to the World Health Organization recommendations. Cases with spermatozoa concentrations of ≤5 million/ml were screened for chromosomal aberrations and Y-chromosomal microdeletions.
The primary cause of infertility was defined for 695 of 1737 patients (~40%). The analyzed causal factors could be divided into absolute (secondary hypogonadism, genetic causes, seminal tract obstruction), severe (oncological diseases, severe sexual dysfunction) and plausible causal factors (congenital anomalies in uro-genital tract, acquired or secondary testicular damage). The latter were also detected for 11 (3.4%) men with proven fertility (diagnoses: unilateral cryptorchidism, testis cancer, orchitis, mumps orchitis). The causal factors behind the most severe forms of impaired spermatogenesis were relatively well understood; causes were assigned: for aspermia in 46/46 cases (100%), for azoospermia in 321/388 cases (82.7%), and for cryptozoospermia in 54/130 cases (41.5%). In contrast, 75% of oligozoospermia cases remained unexplained. The main cause of aspermia was severe sexual dysfunction (71.7% of aspermia patients). Azoospermia patients accounted for 86.4% of all cases diagnosed with secondary hypogonadism and 97.1% of patients with seminal tract obstruction. Of patients with a known genetic factor, 87.4% had extreme infertility (azoo-, crypto- or aspermia). The prevalence of congenital anomalies in the uro-genital tract was not clearly correlated with the severity of impaired sperm production. Previously defined \'potential contributing factors\' varicocele and leukocytospermia were excluded as the primary causes of male infertility. However, their incidence was >2-fold higher (31.0 vs 13.5% and 16.1 vs 7.4%; P < 0.001) in the idiopathic infertility group compared to controls. In addition, the proportions of overweight (or obese) patients and patients suffering from a chronic disease were significantly increased in almost all of the patient subgroups.
The study included only subjects with reduced total spermatozoa counts. Thus, these findings cannot be automatically applied to all male factor infertility cases.
The novel insights and improved clarity achieved in the comprehensive analysis regarding the absolute, causative and plausible factors behind male infertility, as well as the \'potential contributing factors\', will be valuable tools in updating the current clinical guidelines. The study highlights knowledge gaps and reiterates an urgent need to uncover the causes and mechanisms behind, and potential treatments of, oligozoospermic cases, representing the majority of idiopathic infertility patients (86.3%).
The project was financed by the EU through the ERDF, project HAPPY PREGNANCY, no. 3.2.0701.12-004 (M.P., M.L.) and the Estonian Research Council: grants PUT181 (M.P.) and IUT34-12 (M.L.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. TRAIL  REGISTRATION NUMBER: Not applicable.