Managing couples with recurrent miscarriage: A narrative review and practice recommendations.

There is significant variation in practice when managing couples with recurrent miscarriage (RM), with guidelines differing on the definition of RM, recommended investigations, and treatment options. In the absence of evidence-based guidance, and following on from a paper by the authors-FIGO Good Practice Recommendations on the use of progesterone in the management of recurrent first-trimester miscarriage-this narrative review aims to propose a global holistic approach. We present graded recommendations based on best available evidence.

Factors Affecting Remote Workers' Job Satisfaction in Utah: An Exploratory Study.

With structural changes in work arrangements, employee retention becomes more important for organizational success. Guided by the Ability, Motivation, Opportunity (AMO) framework, this study investigated the factors affecting remote workers' job satisfaction and personal wellbeing in Utah. From a sample of n = 143 remote workers, the study used a correlational design to identify the significant predictors of job satisfaction and personal wellbeing. It mapped the relationships between significant predictors of job satisfaction and personal wellbeing and explored the role of human resources (HR) policies and organizational culture in a remote work environment. Results showed intrinsic motivation, affective commitment, opportunity, and amotivation affected employee job satisfaction, while self-efficacy, amotivation, and job satisfaction affected personal wellbeing. A structural equation model (SEM) showed that remote workers with higher levels of self-efficacy, lower amotivation, and higher job satisfaction were likely to have greater personal wellbeing compared to others. When exploring the role of HR, findings showed that HR bundles and organizational culture indirectly affected job satisfaction but had a direct effect on the most important predictors of job satisfaction and personal wellbeing. Overall, results demonstrated the interconnectivity of HR practices, AMO factors, job satisfaction, and personal wellbeing.

Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? - a cohort study and systematic review of the literature.

OBJECTIVE: There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to overdiagnosis and treatment without an improvement in clinical outcomes. The objective of our study was to assess the prevalence of inherited and acquired thrombophilia in a large cohort of women with a history of early RM using internationally agreed diagnostic criteria and inclusion parameters and compare it to the meta-analysis results of existing literature. METHODS: DESIGN: Retrospective cohort study and systematic review of literature. SETTING: This is a retrospective cohort study set-up in two dedicated tertiary centres for women with RM in Southwest London and Surrey. We reviewed all the available literature related to causes of RMs. We ascertained the prevalence of thrombophilia in the study population and compared it with historical and published prevalence in the general population. PARTICIPANTS: 1155 women between 2012 and 2017. All patients had three or more first trimester miscarriages and a full thrombophilia screen. RESULTS: The overall prevalence of thrombophilia in our study population is 9.2% (106/1155) with 8.1% (94/1155) of cases positive for inherited thrombophilia, which is similar to the general population; Factor V Leiden (4.9%; 57/1155) and prothrombin gene mutation (2.9%; 34/1155) were the most common inherited thrombophilias, while only 1% (12/1155) tested positive for acquired thrombophilia. Persistent positive lupus anticoagulant (LA) was found in 0.5% (6/1155) and persistent positive anticardiolipin (ACL) antibodies with a value ≥40 U/mL was found in 0.5% (6/1155) of patients. Tests for LA/ACL were performed a minimum of 12 weeks apart thus meeting the revised Sapporo criteria for a diagnosis of antiphospholipid syndrome. CONCLUSION: The findings of our study demonstrate that the prevalence of inherited thrombophilia is similar in women with RM to that in the general population. Similarly, the prevalence of acquired thrombophilia, using the revised Sapporo criteria, in the cohort of RMs is similar to that in the general population. Therefore, we do not recommend investigation or treatment of inherited or acquired thrombophilia in women with RM. PROSPERO REGISTRATION NUMBER: CRD42020223554.

High Prevalence of Diabetes Mellitus in a Cohort of Patients with Chronic Obstructive Pulmonary Disease in Trinidad, West Indies.

OBJECTIVES: Both chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM) are highly prevalent in Trinidad, West Indies. Our objective was to evaluate the prevalence of DM in a cohort of Trinidadian patients with COPD and investigate the possible impact of diabetes on COPD using standard outcome measures, that is, lung function, exacerbations, quality of life and depression questionnaires, as well as mortality. MATERIALS AND METHODS: This was a cross-sectional follow-up study utilizing a cohort of 105 patients from chest clinics in the three major general hospitals in Trinidad. RESULTS: Diabetes was diagnosed based on a glycated hemoglobin (HbA1c) level of ≥6.5% (or a prior self-reported history), and for pre-diabetes, of 5.7%-6.4%. Of 105 patients, 40% fulfilled the criteria for diabetes and 40% for pre-diabetes. Of those diagnosed with diabetes, 38% obtained this diagnosis de novo. A history of intravenous corticosteroid use was associated with higher HbA1c levels (p=0.043) upon diagnosis. The percentage of predicted forced vital capacity was negatively related to HbA1c (p=0.033), but those with diabetes also had a greater body mass index (p=0.001). After a 1-year follow-up, mortality was significantly greater among patients with diabetes (p=0.026). Patients with at least one exacerbation in the past year or poorer lung function parameters had worse quality of life (p≤0.040) and depression (p≤0.018) scores. Notably, 31.4% of the total cohort exhibited clinically significant depression scores. CONCLUSION: This study revealed that a high proportion of COPD patients in tertiary care had diabetes or pre-diabetes.

Three-dimensional indices of renal perfusion in normal pregnancy and pre-eclampsia.

INTRODUCTION: We compared renal perfusion in normal pregnant women and women with pre-eclampsia using three-dimensional (3D) ultrasound. We measured the flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which are believed to reflect vascularity and flow intensity. METHODS: Fourteen patients with normal pregnancy and 16 patients with pre-eclampsia were recruited. Imaging was conducted using a Voluson E8 machine and a 6-MHz trans-abdominal probe. The inferior border of the maternal left kidney was scanned. Volumes were acquired using 3D power Doppler angiography (3D-PDA). The FI, VI and VFI were generated using 'histogram' facility. RESULTS: Maternal characteristics between normal pregnant women and women with pre-eclampsia were not different in terms of maternal age, gestation or body mass index. Depth of insonnation was not different between groups. The FI, VI and the VFI were not different between groups. The mean (SD) for FI was 27.9 (7.4) vs. 27.1 (6.5) between women with normal pregnancy vs. women with pre-eclampsia. For VI, mean (SD) was 72.3(31.6) vs. 79.4 (28.7) respectively. For VFI, mean (SD) was 20.8 (10.8) vs. 20.8 (8.1) respectively. Using the Mann-Whitney U test, no statistical differences between groups were apparent. There was no correlation between FI measurements and maternal creatinine (Pearson's R square = 0.04; p = 0.45) or with maternal urea levels (Pearson's R square = 0.20; p = 0.10). CONCLUSION: Using 3D ultrasound, we failed to demonstrate a difference in maternal renal perfusion in normal pregnancy compared to pre-eclampsia. The lack of observed difference may be a reflection of the high variability in 3D measurements (i.e. poor investigative tool) rather than a true lack of difference in renal perfusion.

Gestational diabetes-Predictors of response to treatment and obstetric outcome.

OBJECTIVE: Evaluate patient characteristics that are predictors of treatment response and outcomes in gestational diabetes STUDY DESIGN: Retrospective cohort of 265 women with gestational diabetes treated with diet/metformin and/or insulin in a single centre over 2 years. RESULTS: Multinomial logistic regression showed that (after adjusting for age and ethnicity) women who were of normal weight were more likely to be on diet and women who were obese were more likely to be on metformin or metformin and insulin(p=0.014). Women who were obese were twice more likely to have labour induced than those with normal weight. Onset of labour was the only parameter significantly associated with a treatment modality among the three groups (p<0.001). There was no difference in the incidence of large for gestational age, neonatal admission, shoulder dystocia or still birth between the three groups. CONCLUSIONS: Maternal BMI appears to be the only parameter that is predictive of need for treatment with metformin/insulin and the modality of treatment does not have an effect on maternal and neonatal outcomes.

Prenatal surgery for spina bifida: a therapeutic dilemma. Proceedings of the SHINE conference, Belfast.

This is a transcript of a scientific conference on the subject of prenatal surgery for spina bifida. It represents the views of three patients, an obstetrician, a postnatal neurosurgeon, a neonatologist, a paediatric neurologist, two surgeons who practice open spina bifida foetal surgery, a fetoscopic surgeon and an obstetrician experienced in randomised trials and systematic reviews. Implications for current practice and recommendations for future research are also discussed in detail.

An Assessment of Fetal Cerebral and Hepatic Perfusion in Normal Pregnancy and Pre-Eclampsia Using Three-Dimensional Ultrasound.

BACKGROUND: Pre-eclampsia and placental causes of intrauterine growth restriction (IUGR) are part of the same spectrum of disorders. In IUGR, there is preferential shunting of blood to the fetal brain at the expense of other organs. We wanted to demonstrate that this also occurs in pre-eclampsia using three dimensional (3D) ultrasound. The 3D indices of perfusion are: flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which reflect tissue vascularity and flow intensity. METHODS: Fourteen normal pregnant women and 14 with diagnosed pre-eclampsia were recruited. Scanning was conducted by 2 observers using a Voluson E8 machine. Perfusion was measured at a pre-defined position within the fetal brain and fetal liver. The power Doppler signals were quantified using the 'histogram facility' to generate 3 indices of vascularity: FI, VI and VFI. The unpaired t-test was used to compare differences between groups. The hypothesis was that fetal brain FI, VI and VFI would be similar between women with normal pregnancy and women with pre-eclampsia, but measurements would be reduced in the fetal liver in women with pre-eclampsia. RESULTS: Maternal characteristics of age, body mass index and gestation were not different between groups. The depth of insonnation did not differ between groups. Fetal cerebral perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 22.4 (5.7) vs. 21.1 (4.3) respectively (p=0.49). For VI, the mean (SD) was as 64.7 (40.4) vs. 79.1 (27.4) respectively (p=0.28). For VFI, the mean (SD) was 14.8 (10.3) vs. 16.1 (5.5) respectively (p = 0.66). Fetal hepatic perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 34.4 (19.9) vs. 27.8 (11.0) respectively (p = 0.28). For VI, mean (SD) was 67.6 (36.0) vs. 87.3 (25.8) respectively (p=0.11). For VFI, the mean (SD) was 19.6 (11.6) vs. 23.1 (10.6) respectively (p=0.42). CONCLUSION: Using 3D ultrasound, we were not able to demonstrate preferential shunting of blood to the fetal brain at the expense of the fetal liver. Due to the high variability of our data, no definite conclusions can be derived from this work. A larger study may be required.

Managing Recurring Obstetric Cholestasis With Metformin.

BACKGROUND: Obstetric cholestasis is a pregnancy-related disorder associated with an adverse pregnancy outcome. It is characterized by generalized pruritus, elevated bile acids, and abnormal liver enzymes. Recent publications show that obstetric cholestasis is associated with, and likely to potentiate, the risk of developing gestational diabetes mellitus. CASE: This case describes an unusual pattern of the disease, in which obstetric cholestasis occurred in five consecutive pregnancies with a different course of the disease in the fifth pregnancy. CONCLUSION: A patient with recurrent cholestasis of pregnancy had worsening disease in her first four pregnancies. In her fifth pregnancy, treatment for gestational diabetes mellitus with metformin was associated with a lowering effect on bile acids and liver enzymes, indicating a possible role for metformin in the management of obstetric cholestasis.

Breathe easy at home: a web-based referral system linking clinical sites with housing code enforcement for patients with asthma.

Asthma, the most significant cause of pediatric morbidity and mortality, is exacerbated by adverse environmental conditions, especially substandard housing. The clinical care provider is often unable to address housing and environmental trigger issues. In Boston, Massachusetts, a web-based referral system called Breathe Easy At Home has been put in place, through which clinicians can refer patients to have their homes inspected for housing code violations that may be contributing to their asthma. Violations will then be brought to the attention of the landlord, who then has the option of redressing the issue or be taken to housing court. By bringing the local public health department, the city's inspectional services department, and the clinical care provider together with the help of a program coordinator, Breathe Easy At Home is able to provide comprehensive care to asthma patients. This program also serves as a replicable model for other cities and jurisdictions to follow.

Delivery outcomes and events in subsequent pregnancies after previous anal sphincter injury.

OBJECTIVE: To assess the mode of delivery following previous anal sphincter injury (ASI), and to evaluate the perineal outcome following a vaginal birth. STUDY DESIGN: Retrospective data search of the hospital Patient Access System on patients who delivered following previous ASI from 2010 to 2012. When a second ASI was sustained, additional information was gathered from the patients' medical notes. Continuous variables were described by counts and percentages and analysed using SPSS version 20. RESULTS: Between January 2010 and July 2012, 138 women with previous ASI delivered at the Rotunda Hospital, of whom 69 (50%) had a spontaneous vaginal delivery (SVD), 13 (9.4%) had an instrumental delivery (11 vacuum, 2 forceps), and 56 (40.6%) had a caesarean section. Of these caesarean sections, 43 (76.8%) were elective, and 13 (23.2%) were emergency. Of the 82 vaginally delivered patients, the majority had a second degree perineal tear or minor lacerations (54/82 and 14/82 respectively) but 11 had a third degree perineal tear following an SVD - a recurrence risk of 13.4%. There was no significant difference in the average birthweight between patients who sustained a second ASI (3644g) compared to those who did not (3680g). None of the patients who had a second ASI developed faecal incontinence symptoms postnatally: two patients developed flatal incontinence which resolved with physiotherapy. CONCLUSION: This study highlights the importance of individualised antenatal assessment in patients with a previous ASI. They may have a personal preference when considering their mode of delivery. A specialist clinic affords them the opportunity for a detailed discussion. In this study, 86.5% of women who delivered their subsequent baby vaginally did not sustain an ASI, while 13.4% had a repeat ASI following vaginal birth. It is therefore important to counsel regarding the incidence of repeat ASI, but also to emphasise that it is generally impossible to confidently predict recurrence antenatally.

Modulating hedgehog signaling can attenuate the severity of osteoarthritis.

Osteoarthritis is associated with the irreversible degeneration of articular cartilage. Notably, in this condition, articular cartilage chondrocytes undergo phenotypic and gene expression changes that are reminiscent of their end-stage differentiation in the growth plate during skeletal development. Hedgehog (Hh) signaling regulates normal chondrocyte growth and differentiation; however, the role of Hh signaling in chondrocytes in osteoarthritis is unknown. Here we examine human osteoarthritic samples and mice in which osteoarthritis was surgically induced and find that Hh signaling is activated in osteoarthritis. Using several genetically modified mice, we found that higher levels of Hh signaling in chondrocytes cause a more severe osteoarthritic phenotype. Furthermore, we show in mice and in human cartilage explants that pharmacological or genetic inhibition of Hh signaling reduces the severity of osteoarthritis and that runt-related transcription factor-2 (RUNX2) potentially mediates this process by regulating a disintegrin and metalloproteinase with thrombospondin type 1 motif-5 (ADAMTS5) expression. Together, these findings raise the possibility that Hh blockade can be used as a therapeutic approach to inhibit articular cartilage degeneration.