Differences in Incidence and Risk Factors of Infertility Between Couples Who Desire a First and Second Child: A Prospective Cohort Study

Background: With the implementation of the two-child policy in China, more couples expressed their desire to have a child. We conducted this study to evaluate the incidence and risk factors of infertility in couples intending to have a first child and second child.Methods: Couples who presented to the pre-pregnancy clinical centers were enrolled from 2013 to 2017. Participants were categorized into “first child intention” and “second child intention” groups based on the number of children they already had. Couples were followed up every three months until pregnancy or 12 months. Data regarding the sociodemographic characteristics, history of reproduction and gynecology, history of male disease, and laboratory and imaging examination results were collected. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated and adjusted for potential confounding factors.Results: The overall infertility incidence was 16.95% (369/2177). The infertility incidence of “first child intention” and “second child intention” was 19.30% (355/1839) and 4.14% (14/338). The study showed great differences in infertility risk factors between two groups. Risk factors for “first child intention” infertility included advanced age (>35 years), abnormal body mass index (BMI), longer menstrual durations, endometrial polyps, polycystic ovarian syndrome (PCOS), salpingostomy, and history of mycoplasma. However, in “second child intention” group, clinical risk factor was slightly different, such as leiomyoma, higher age (>40 years).Conclusion: The incidence and risk factors of infertility are significantly different between “first child intention” group and “second child intention” group. Early and targeted intervention for couples in different groups at high risk can help reduce infertility and social burden.

Ideal cardiovascular health duration and risk of chronic kidney disease and cardiovascular disease

ObjectiveIncreasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management. Yet, little is known regarding cardiovascular risks associated with the length of favourable cardiometabolic profile. In this context, we examined whether the duration of strictly ideal cardiovascular health (CVH), based on body mass index, blood pressure, fasting glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD) in mid-to-late life.MethodsFrom the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Cox proportional hazards models were employed to assess CKD and CVD risks, adjusting for age, sex, education level, examination sites and renal markers.ResultsOver a median follow-up of 15.0 years, 1401 cases of CKD and 493 cases of CVD were newly developed. Compared with participants with <5 years of ideal CVH duration, HR (95% CI) of those who maintained for 5–<10 years or ≥10 years had negatively graded risks for CKD (5–<10 years, 0.63 (0.39 to 0.93); ≥10 years, 0.33 (0.15 to 0.74)) and CVD (5–<10 years, 0.83 (0.54 to 1.27); ≥10 years, 0.22 (0.08 to 0.60)). In parallel, participants with delayed decline to suboptimal level had lower disease risks compared with counterparts with consistently suboptimal CVH.ConclusionOur findings confer that maintaining favourable health behaviours and clinical risk factor levels in midlife will improve later-life cardiovascular outcomes.

Combining renal cell arrest and damage biomarkers to predict progressive AKI in patient with sepsis

Background Sepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Early identifying high risk patients for AKI progression is a major challenge in patients with septic AKI. Methods This is a prospective, multicenter cohort study which enrolled adult patients with sepsis and initially developed stage 1 or 2 AKI in the intensive care unit from January 2014 to March 2018. AKI was diagnosed and staged according to 2012 KDIGO-AKI guidelines. Renal cell arrest biomarkers (urinary TIMP2*IGFBP7, u[TIMP-2]*[IGFBP7]) and renal damage biomarkers (urinary KIM-1[uKIM-1] and urinary IL-18 [uIL-18]) were measured at time of AKI clinical diagnosis, and the performance of biomarkers for predicting septic AKI progression alone or in combination were evaluated. The primary outcome was AKI progression defined as worsening of AKI stage. The secondary outcome was AKI progression with subsequent death during hospitalization. Results Among 433 screened patients, 149 patients with sepsis and stage 1 or 2 AKI were included, in which 63 patients developed progressive AKI and 49 patients subsequently died during hospitalization. u[TIMP-2]*[IGFBP7], uKIM-1 and uIL-18 independently predicted the progression of septic AKI in which u[TIMP-2]*[IGFBP7] showed the greatest AUC (0.745; 95%CI, 0.667-0.823) as compared to uKIM-1 (AUC 0.719; 95%CI 0.638-0.800) and uIL-18 (AUC 0.619; 95%CI 0.525-0.731). Combination of u[TIMP-2]*[IGFBP7] with uKIM-1 improved the performance of predicting septic AKI progression with AUC of 0.752. u[TIMP-2]*[IGFBP7], alone or combined with uKIM-1/uIL-18, improved the risk reclassification over the clinical risk factor model alone both for the primary and secondary outcomes, as evidenced by significant category-free net reclassification index. Conclusions Combination of renal cell arrest and damage biomarkers enhanced the prediction of AKI progression in patients with sepsis and improved risk reclassification over the clinical risk factors.

Utility and significance of clinical risk factor scoring model in predicting central compartment lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC)

Objectives: To establish and discuss the significance of a clinical risk factor scoring model in predicting central compartment lymph node metastasis (CLNM) (level VI) in patients with papillary thyroid cancer (PTC). Methods: A retrospective analysis was performed on 412 patients who underwent surgical treatment for PTC who were admitted to the Second Hospital of Hebei Medical University between July 2016 and May 2017, with the patients being divided into a CLNM group and a non-metastasis (NM) group. Risk factors such as sex, age, tumor diameter, capsular invasion, multifocality, and tumor location were recorded for scoring via maximum likelihood estimation (MLE)-based discriminant analysis. The scoring model was used for prospective analysis of CLNM in another 104 patients. Besides, the discriminant function that was developed using the risk factors based on the retrospective data derived from the 412 patients was evaluated by plugging the retrospective data in for specified variables, with a higher score indicating a greater risk of developing CLNM. Clinical diagnosis of CLNM was based on postoperative paraffin section pathology, which was adopted as the criterion to assess discriminative accuracy in the prospective and retrospective groups. Results: The discriminative accuracy of the scoring model was 71.8% in the retrospective group and 72.2% in the prospective group. Conclusions: The scoring model enables simplified, quantitative analysis of CLNM in PTC patients. The scoring model has clinical significance in that it provides a basis for the choice of operation, personalized postoperative treatment, and prognosis of PTC. doi: https://doi.org/10.12669/pjms.38.1.4450 How to cite this:Shen W, Pan X, Li Q. Utility and significance of clinical risk factor scoring model in predicting central compartment lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4450 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Interrelation between Sleep Bruxism and Obstructive Sleep Apnea: Literature Review

Obstructive sleep apnea (OSA) is a clinical risk factor for sleep bruxism (SB). Although no clear causative link has been defined, both conditions are inter related to sleep-related arousal reactions [1]. A literature review was conducted on PubMed and ScienceDirect databases for 2000–2021 period. The majority of studies revealed an association between OSA and SB events.

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Pravastatin to Prevent Preeclampsia and its Effects on sFlt1/PLGF Levels

Objectives To evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing preeclampsia and the maternal and perinatal outcomes and the sFlt1/PLGF ratio. Study Design This is an open labelled RCT part of INOVASIA trial. Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery doppler examination at 10-20 weeks gestational age. The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20 mg twice daily) starting from 14-20 weeks gestation until delivery. Research blood samples were collected before the first dose of pravastatin and before delivery. The main outcome was the rate of maternal preeclampsia, maternal-perinatal outcomes, and sFlt-1, PLGF, sFlt-1/PlGF ratio and sEng levels. Results The rate of preeclampsia was (non-significantly) lower in the pravastatin group compared with the control group (17.5% vs 35%). The pravastatin group also had a (non-significant) lower rate of severe preeclampsia, HELLP syndrome, acute kidney injury and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly (p=0.048) lower in the pravastatin group (n=4) compared with the controls (n=12). Neonates in the pravastatin group had significantly higher birthweights (2931 + 537 vs 2625 + 872 g; p=0.006), lower Apgar scores < 7 (2.5 vs 27.5%, p=0.002), composite neonatal morbidity (0 vs 20%, p=0.005) and NICU admission rates (0 vs 15%, p=0.026). All biomarkers show a significant deterioration in the control group compared with non significant changes in the pravastatin group. Conclusions Pravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance.

Plasma SerpinA5 in conjunction with uterine artery pulsatility index and clinical risk factor for the early prediction of preeclampsia

Object This study aimed to combine plasma protein SerpinA5 with uterine artery doppler ultrasound and clinical risk factor during the first trimester for prediction of preeclampsia. Methods and materials This study was a nested cohort study and was divided into the screening set and developing set. The plasma was collected during the first trimester (11+0–13+6 weeks), at the same time, UtA-PI was detected and recorded with four-dimensional color Doppler ultrasound. These pregnancies were followed up until after delivery. The plasma proteins were examined using ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) and enzyme linked immunosorbent assay (ELISA). Placental samples preserved after delivery were analysed by immunohistochemistry. Clinical risk factors were obtained from medical records or antenatal questionnaires. Upregulation or downregulation of SerpinA5 expression in TEV-1 cells was performed to investigate the role of SerpinA5 in trophoblasts invasion. Results We demonstrated that SerpinA5 levels were greater not only in preeclampsia placental tissue but also in plasma (both p<0.05), and we found that SerpinA5 may interfere with trophoblastic cell invasion by inhibiting MSP. SerpinA5 may be a potential predictor of preeclampsia. What is more, the sensitivity and specificity of predictive power were strengthened when plasma SerpinA5 was combined with UtA-PI and pre-pregnancy BMI & family history of PE for prediction of preeclampsia. Conclusion These findings showed that placenta-derived plasma SerpinA5 may be a novel biomarker for preeclampsia, which together with uterine artery Doppler ultrasound and clinical risk factor can more effectively predict preeclampsia.

Asymptomatic COVID-19 in the elderly: dementia and viral clearance as risk factors for disease progression.

Background: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression. Methods: We established a medical surveillance team monitoring 63 geriatric institutions. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied. Results: After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 21/39(54%) pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died(median day 13.5,IQR 12). Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as a risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027). On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012). No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2 nucleocapsid protein). Conclusions: In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection.