The value of a mobile educative Application additional to Standard counselling on aspirin Adherence in Pregnancy: the ASAP study, a randomised controlled trial.

Objective: To assess the added value of a novel, mobile educative application to standard counselling on aspirin adherence during pregnancy versus standard counselling alone. Methods: Participants were randomly assigned for additional use of a mobile educative application or standard counselling alone. Main outcome measures were adherence to aspirin measured by two validated questionnaires: Simplified Medication Adherence Questionnaire (SMAQ), Believes and Behaviour Questionnaire (BBQ), and patients reported tablet intake >90%. Results: A total of 174 women with an indication for aspirin during pregnancy were included. The questionnaires were filled in by 126 out of the 174 participants (72.4%). Similar results were found in the app group and the standard counselling groups for both validated questionnaires. Tablet intake >90% was seen in 88.7% and 87.5% (p = 0.834) of the app group and standard counselling group respectively. Subgroup analyses demonstrated a negative effect of BMI and a positive effect of educational level on adherence. Conclusions: Our study revealed no added effect of a novel, mobile educative application to standard counselling on aspirin adherence during pregnancy. Tablet intake was equally high in both groups probably explained by our high educated population. Innovation: Future studies should focus on tailored counselling on medication to pregnant women's needs including medication reminders, addressing concerns, adequate health literacy and side effects, offering rewards to further stimulate aspirin adherence in pregnancy with optimal outcome for mother and their neonate.

The efficacy of sensory nerve coaptation in DIEP flap breast reconstruction - Preliminary results of a double-blind randomized controlled trial.

BACKGROUND: Sensory nerve coaptation has great potential to restore sensation after autologous breast reconstruction. However, blinded and randomized studies are lacking. We therefore present the preliminary results of our ongoing double-blinded randomized controlled trial that compares sensory recovery of innervated versus non-innervated DIEP flaps. METHODS: Patients who underwent DIEP flap breast reconstruction between July 2019 and February 2022 were included and randomized. The anterior cutaneous branch of the second or third intercostal nerve was coapted. Pre- and postoperative sensory testing was performed with Semmes-Weinstein Monofilaments, Pressure Specified Sensory Device, and a thermostimulator, for tactile and temperature thresholds. RESULTS: This interim analysis comprised 41 patients contributing 29 innervated and 38 non-innervated breasts. At 24 months of follow-up, the mean monofilament value of the flap skin was lower in innervated than in non-innervated flaps (4.48 vs. 5.20, p = 0.003). Touch thresholds were lower the center of the innervated flaps (47.8 vs. 71.2 g/mm2, p = 0.036), and heat pain was more often imperceptible in non-innervated flaps (42.1% vs. 10.3%, p = 0.004). No adverse events were associated with sensory nerve coaptation. CONCLUSIONS: These preliminary results indicate superior sensibility and recovery of protective sensation in innervated compared with non-innervated DIEP flaps. Although the results of the completed trial must be awaited to establish the full clinical impact, including highly anticipated quality of life outcomes, we encourage continuation of scientific and clinical efforts in this promising technique.

Sensory recovery and the role of innervated flaps in autologous breast reconstruction-a narrative review.

Background and Objective: Continuing (micro)surgical developments result in satisfactory aesthetic outcomes after autologous breast reconstruction. However, sensation recovers poorly and remains a source of dissatisfaction and potential harm. Sensory nerve coaptation is a promising technique to improve sensation in the reconstructed breast. Methods: In this literature review an overview of current knowledge about sensory recovery in autologous breast reconstruction and the role of innervated flaps is presented. A thorough PubMed search was conducted, using the terms "autologous breast reconstruction", "innervated" and "sensation". Key Content and Findings: The breast skin is predominantly innervated by the second until sixth intercostal nerve. Some nerves can occasionally be spared during mastectomy, especially during nipple-sparing mastectomy, but transection of sensory nerves is inevitable and leads to impaired sensation. Besides unpleasant, this is unanticipated by patients and negatively influences quality of life. Coaptation between the third anterior intercostal nerve and a sensory nerve from the donor site improves sensory recovery. The donor site and nerve vary, depending on the flap type chosen. The sensory nerves from the commonly used abdominal DIEP flap originate from the 7th until 12th thoracic spinal nerves. Non-abdominal flaps, including the back, buttocks, or thigh area, can also be accompanied with a sensory nerve. Nerve coaptation can be performed directly, or by using grafts or conduits to obtain tensionless repair if necessary. It can be utilized in both immediate as well as delayed autologous breast reconstruction. No adverse outcomes of nerve coaptation have been described. And, most importantly: improved sensory recovery improves patient satisfaction and quality of life. Conclusions: Restoring sensation is, besides restoring aesthetic appearance, an important goal in breast reconstruction. Current evidence unambiguously demonstrates superiority of innervated flaps compared to non-innervated flaps. Sensory recovery initiates earlier and it approaches normal sensation more closely in innervated flaps, without associated risks or extensive increase in operating time. This improves patient satisfaction and quality of life. It is, therefore, a valuable addition to autologous breast reconstruction. These findings encourage implementation of sensory nerve coaptation in standard clinical care.

Hypertensive disorders of pregnancy after multifetal pregnancy reduction: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on hypertensive disorders of pregnancy (HDP) after multifetal pregnancy reduction (MFPR). METHODS: A comprehensive search in PubMed, Embase, Web of Science, and Scopus was performed. Prospective or retrospective studies reporting on MFPR from triplet or higher-order to twin compared to ongoing (i.e., non-reduced) triplets and/or twins were included. A meta-analysis of the primary outcome HDP was carried out using a random-effects model. Subgroup analyses of gestational hypertension (GH) and preeclampsia (PE) were performed. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Thirty studies with a total of 9,811 women were included. MFPR from triplet to twin was associated with a lower risk for HDP compared to ongoing triplets (OR 0.55, 95% CI, 0.37-0.83; p = 0.004). In a subgroup analysis, the decreased risk of HDP was driven by GH, and PE was no longer significant (OR 0.34, 95% CI, 0.17-0.70; p = 0.004 and OR 0.64, 95% CI, 0.38-1.09; p = 0.10, respectively). HDP was also significantly lower after MFPR from all higher-order (including triplets) to twin compared to ongoing triplets (OR 0.55, 95% CI, 0.38-0.79; p = 0.001). In a subgroup analysis, the decreased risk of HDP was driven by PE, and GH was no longer significant (OR 0.55, 95% CI 0.32-0.92; p = 0.02 and OR 0.55, 95% CI 0.28-1.06; p = 0.08, respectively). No significant differences in HDP were found in MFPR from triplet or higher-order to twin versus ongoing twins. CONCLUSIONS: MFPR in women with triplet and higher-order multifetal pregnancies decreases the risk of HDP. Twelve women should undergo MFPR to prevent one event of HDP. These data can be used in the decision-making process of MFPR, in which the individual risk factors of HDP can be taken into account.

The effect of low-dose aspirin on platelet function during pregnancy compared to placebo: An explorative study.

OBJECTIVES: To evaluate the effect of aspirin 80 mg compared to placebo on platelet function tests in the second and third trimester of pregnancy. STUDY DESIGN: An explorative study was performed to assess laboratory platelet function in a subpopulation of the APRIL trial: a randomized double-blind trial comparing aspirin 80 mg once daily to placebo for the prevention of recurrent preterm birth. Platelet function was measured between 18 and 22, and between 28 and 32 weeks gestational age with three platelet function tests: VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B2 (TxB2). Medication adherence was evaluated by pill counts, self-reported diaries and structured interviews. RESULTS: We included 11 women, six in the aspirin and five in the placebo group. In women receiving aspirin, platelet function was significantly lower compared to women receiving placebo for all three tests: VerifyNow® Aspirin Reaction Units (450.5 vs 648.0, p = 0.017); Chronolog LTA (9.5% vs 94.5%, p = 0.009); serum TxB2 levels (11.9 ng/mL versus 175.9 ng/mL, p = 0.030). For all three tests, platelet function did not differ between the second and third trimester of pregnancy in the aspirin group. In the placebo group, serum TxB2 levels were significantly higher in the third trimester. One non-adherent participant in the aspirin group showed results similar to the placebo group. CONCLUSION: Aspirin 80 mg has a clear inhibitory effect on laboratory platelet function during pregnancy compared to placebo. This effect is similar in the second and third trimester of pregnancy.

Rat donor lung quality deteriorates more after fast than slow brain death induction.

Donor brain death (BD) is initiated by an increase in intracranial pressure (ICP), which subsequently damages the donor lung. In this study, we investigated whether the speed of ICP increase affects quality of donor lungs, in a rat model for fast versus slow BD induction. Rats were assigned to 3 groups: 1) control, 2) fast BD induction (ICP increase over 1 min) or 3) slow BD induction (ICP increase over 30 min). BD was induced by epidural inflation of a balloon catheter. Brain-dead rats were sacrificed after 0.5 hours, 1 hour, 2 hours and 4 hours to study time-dependent changes. Hemodynamic stability, histological lung injury and inflammatory status were investigated. We found that fast BD induction compromised hemodynamic stability of rats more than slow BD induction, reflected by higher mean arterial pressures during the BD induction period and an increased need for hemodynamic support during the BD stabilization phase. Furthermore, fast BD induction increased histological lung injury scores and gene expression levels of TNF-α and MCP-1 at 0.5 hours after induction. Yet after donor stabilization, inflammatory status was comparable between the two BD models. This study demonstrates fast BD induction deteriorates quality of donor lungs more on a histological level than slow BD induction.

Patients' perspective on aspirin during pregnancy: a survey.

OBJECTIVE: To elucidate patients' knowledge and counseling perspective on aspirin reducing the risk of hypertensive disorders of pregnancy (HDP). METHODS: A quantitative survey was performed including women who are members of the patient orgasnization Dutch HELLP Foundation due to a history of HDP. RESULTS: Awareness of the risk-reducing effect of aspirin on HDP was present in 51.9% of the 189 women. The majority was informed by their gynecologist (89.8%) and preferred to be informed by a gynecologist (79.4%), at the postpartum checkup (42.3%) or in the consecutive pregnancy (30.7%), both orally and written (62.4%). CONCLUSION: Half of the women with a history of HDP were aware of the risk-reducing effect of aspirin in a consecutive pregnancy.

The relationship of a Prothrombin G20210A mutation or a factor V Leiden mutation and on-aspirin platelet (re-)activity.

INTRODUCTION: The interplay between platelets and pro-thrombotic factors may have been under-investigated in the identification of aspirin users at high risk for cardiovascular event reoccurrences. There is growing evidence that a Prothrombin G20210A (FII) or a Factor V Leiden (FVL) mutation might increase platelet activity. Subsequently, this study assessed on-aspirin platelet (re-)activity in non-pregnant participants with a FII - or a FVL mutation in comparison with non-pregnant data derived from controls. METHODS: This study was conducted with data derived from the follow-up FRUIT-RCT. This is a unique cohort namely, participants without a history of cardiovascular disease or thrombotic events, but who are a carrier of a pro-thrombotic mutation. All participants were instructed to ingest aspirin once daily for 10 days. Platelet (re-)activity was measured by the PFA Closure Time (PFA-CT), the VerifyNow (VN-ARU), and serum Thromboxane B2 (sTxB2) levels. RESULTS: In total, eight participants with a FII-, 15 with a FVL mutation, and 21 controls were included. The FII mutation carriers demonstrated significantly higher on-aspirin platelet (re)-activity (PFA-CT, -92 sec.; VN-ARU, +37 ARU) vs. controls. The FVL carriers demonstrated similar on-aspirin platelet (re-)activity vs. controls. The sTxB 2 levels were similar in either of the carrier groups vs. controls. CONCLUSION: We feel these data are suggestive of increased on-aspirin platelet (re-)activity, as measured by the PFA-200 and the VerifyNow, in non-pregnant carriers of a FII-mutation, but not in carriers of FVL-mutation. Interestingly, this increased on-aspirin platelet (re-)activity is present in spite of low sTxB2 levels.

Resistance of aspirin during and after pregnancy: A longitudinal cohort study.

OBJECTIVES: The objective of this study is to investigate possible changes in aspirin resistance during and after pregnancy over time. STUDY DESIGN: A longitudinal cohort study in obstetric high risk women with an indication for aspirin usage during pregnancy to prevent placenta mediated pregnancy complications. MAIN OUTCOME MEASURES: Aspirin resistance measured in the first, second and third trimester of pregnancy and at least three months postpartum by four complementary test: PFA-200, VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B2 (TxB2) level measurements. Correlation between the devices was investigated. RESULTS: In total, 23 pregnant women participated in the present study. Aspirin resistance according to the PFA-200, VerifyNow®, Chronolog LTA and serum TxB2, was 30.4%, 17.4%, 26.1% and 23.8% respectively. Resistance by any device was 69.6%. Aspirin resistance measured by the VerifyNow®, Chronolog LTA, serum TxB2 and aspirin resistance by any device during pregnancy was demonstrated more frequently than aspirin resistance after pregnancy. Correlation between the different devices was weak. CONCLUSION: Aspirin resistance was found in a considerable part of the participants. Considerable variation between participants, within participants over time and between the different devices was found. Prevalence of aspirin resistance during pregnancy differs from after pregnancy. More research on aspirin resistance and clinical obstetric outcome is needed.

Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy.

Preeclampsia is a frequent gestational hypertensive disorder with equivocal pathophysiology. Knockout of peptide hormone ELABELA (ELA) has been shown to cause preeclampsia-like symptoms in mice. However, the role of ELA in human placentation and whether ELA is involved in the development of preeclampsia in humans is not yet known. In this study, we show that exogenous administration of ELA peptide is able to increase invasiveness of extravillous trophoblasts in vitro, is able to change outgrowth morphology and reduce trophoblast proliferation ex vivo, and that these effects are, at least in part, independent of signaling through the Apelin Receptor (APLNR). Moreover, we show that circulating levels of ELA are highly variable between women, correlate with BMI, but are significantly reduced in first trimester plasma of women with a healthy BMI later developing preeclampsia. We conclude that the large variability and BMI dependence of ELA levels in circulation make this peptide an unlikely candidate to function as a first trimester preeclampsia screening biomarker, while in the future administering ELA or a derivative might be considered as a potential preeclampsia treatment option as ELA is able to drive extravillous trophoblast differentiation.

Recovery of second trimester pre-eclampsia after fetal reduction of a triplet.

Women with a multiple pregnancy are at increased risk of developing hypertensive disorders of pregnancy. We describe a case of a dichorionic triamniotic triplet pregnancy complicated by severe hypertension, proteinuria and maternal symptoms, fitting with the diagnosis of pre-eclampsia, apart from the early gestational age of only 16 weeks. After reduction of the monochorionic pair, the disease resolved and pre-eclampsia was diagnosed again at 30 weeks of gestation, resulting in a delivery on maternal indication at 33 weeks of gestation. In a review of the literature, we found six papers including eight cases on multifetal pregnancy reduction on maternal indication. Multifetal pregnancy reduction resulted in a prolongation of pregnancy of two to 21 weeks and may be considered in extreme early onset pre-eclampsia in dichorionic multiple pregnancies.

Fertility in women of late reproductive age: the role of serum anti-Müllerian hormone (AMH) levels in its assessment.

INTRODUCTION: Fertility is referred to the capability for having offspring and can be evaluated by fertility rate. Women's fertility is strictly dependent on individual's age. The fertility peak occurs in the early 20s, and it starts to decline in the third and fourth decades of life (falling sharply after age 35). AIM: The aim of this work is to review the available data concerning fertility in women of late reproductive age, especially the role of serum anti-Müllerian hormone (AMH) levels. RESULTS: There are a lot of factors responsible for decrease of fertility in women of late reproductive age. These factors can be classified as oocyte-dependent (decrease in oocyte quantity and quality) and oocyte-independent (reproductive organs [uterus, oviducts] status and general health). Anti-Müllerian hormone (AMH) is a dimeric glycoprotein of the transforming growth factor-ß (TGF-ß) superfamily produced directly by the ovarian granulosa cells of secondary, preantral, and early antral follicles. It has been used as an ovarian reserve marker since 2002. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women. Evaluation of AMH's predictive value in the naturally aging population is important for counseling women about reproductive planning as well as for treatment planning for women experiencing hormone-sensitive gynecological conditions such as endometriosis and fibroids. CONCLUSIONS: AMH can be considered as an indicator of fertility in late reproductive age women and pregnancy outcome in assisted reproductive technology cycles. AMH can strongly predict poor response in the controlled ovarian stimulation.

Health-related quality of life is unimpaired in children and adolescents with Marfan syndrome despite its distinctive phenotype.

AIM: Marfan syndrome (MFS) is a progressive, life-threatening genetic disorder of the connective tissue, which causes impaired quality of life (QoL) in adults. This study investigated the quality of life in children and adolescents, taking into account their gender, age and how MFS affected their organs. METHODS: This prospective nonrandomised single-centre study included 46 patients with verified MFS with a mean age of 10.98 years (±3.72). QoL was measured using the self-reported, multidimensional KINDL-R questionnaire and compared with an age-matched control group of 174 children and adolescents. RESULTS: No significant overall reduction of QoL was found. Total QoL scores for patients diagnosed at four to seven years were the same as the control group (77.65 ± 9.37 versus 77.06 ± 11.72), but they were higher for patients aged eight to 16 years (75.15 ± 9.19 versus 70.46 ± 11.35, p = 0.025). No gender-specific differences or impairments in QoL during adolescence were observed (p > 0.05). Analysis of the effect of organ manifestation on QoL showed better or equal QoL scores (p > 0.05), despite distinctive phenotypes such as ectopia lentis. CONCLUSION: QoL was fairly good in paediatric patients with MFS, and there was no impairment during adolescence. Despite the distinctive phenotype, quality of life was unimpaired in younger patients.

Functional hypothalamic amenorrhea and its influence on women's health.

INTRODUCTION: Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea. There are three types of FHA: weight loss-related, stress-related, and exercise-related amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. AIM: The aim of this work is to review the available data concerning the effects of FHA on different aspects of women's health. RESULTS: Functional hypothalamic amenorrhea is related to profound impairment of reproductive functions including anovulation and infertility. Women's health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects. CONCLUSIONS: FHA patients should be carefully diagnosed and properly managed to prevent both short- and long-term medical consequences.

Memorandum on the use of information technology to improve medication safety.

BACKGROUND: Information technology in health care has a clear potential to improve the quality and efficiency of health care, especially in the area of medication processes. On the other hand, existing studies show possible adverse effects on patient safety when IT for medication-related processes is developed, introduced or used inappropriately. OBJECTIVES: To summarize definitions and observations on IT usage in pharmacotherapy and to derive recommendations and future research priorities for decision makers and domain experts. METHODS: This memorandum was developed in a consensus-based iterative process that included workshops and e-mail discussions among 21 experts coordinated by the Drug Information Systems Working Group of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS). RESULTS: The recommendations address, among other things, a stepwise and comprehensive strategy for IT usage in medication processes, the integration of contextual information for alert generation, the involvement of patients, the semantic integration of information resources, usability and adaptability of IT solutions, and the need for their continuous evaluation. CONCLUSION: Information technology can help to improve medication safety. However, challenges remain regarding access to information, quality of information, and measurable benefits.

Cushing's syndrome in pregnancy: a case report and mini review of the literature.

Adrenal diseases in pregnant women are diagnosed relatively rarely. The main cause of hypercortisolemia during pregnancy is Cushing's syndrome related to adrenal adenoma. It is important to diagnose Cushing's syndrome in pregnant women because it can lead to significant maternal and foetal complications and morbidity. However, due to physiological endocrine changes and symptoms in pregnant women the diagnosis of this disorder can be a challenge. One current case describes a 38-year-old pregnant woman with hypertension, oedema and an adrenal tumour. At the beginning, Conn syndrome was suspected, but after careful analysis Cushing's syndrome (with an adenoma of the right adrenal gland) was diagnosed. After delivery and 5 weeks of pharmacological treatment the patient underwent right side adrenalectomy by laparoscopy.

Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study.

Familial Mediterranean fever (FMF) is the most inherited common autoinflammatory disease (AID) with mutations in the MEFV (MEditerraneanFeVer) gene.The Mor- and Pras-Score modified for children and C-reactive protein (CRP) were used to assess FMF disease severity in Germany. We evaluate the applicability of the 2 severity scores and the correlations between ethnic origin, phenotype, and genotype.Among 242 children (median 5 age at diagnosis), we detected 431 pyrin mutations and 22 different sequence variants, including one new mutation (p.Gly488Asp). The 5 most -frequent alterations were p.Met694Val (55.2%), p.Met680lle (11.8%), p.Val726Ala (10%), p.Glu148Gln (7.9%) and p.Met694IIe (2.3%). The prevailing ancestries of 223 cases were Turkish (82.5%) and Lebanese (8.1%). Homozygous p.Met694Val substitution (30.2%) was associated with a more severe disease activity by Mor-Score, as well as with a higher mean CRP (74 mg/l) compared to patients with other mutations. Indeed, Mor- and Pras-Score were inconsistent with each other. A typical distribution of mutations in different ethnic populations was obvious, but not statistically verifiable due to the low number of cases.The homozygous p.Met694Val substitution was associated with a more severe disease activity in our German cohort. The common severity scores were inconsistent in -children.

Osteoporosis and polypharmacy.

Osteoporosis is very common in elderly patients. Despite the severe health-related consequences for individual patients and the socioeconomic costs caused by osteoporotic fractures, treatment rates are still low. Due to drug interactions and patient compliance, polypharmacy is often mentioned as a reason for undertreatment. Several drugs have a direct or indirect effect on bone metabolism. The present paper discusses the risk of interactions of anti-osteoporotic drugs (oral and parenteral bisphosphonates, raloxifene, strontium ranelate, teriparatide, and denosumab) with other common medications in elderly patients and their impact on bone metabolism and fracture risk. In summary, the number and risk of drug interactions of all common anti-osteoporotic drugs are small and clinically rather irrelevant. However, patients with a polypharmacy are at a higher risk of fractures and should receive osteoporosis treatment, if indicated.