Management of gestational hypertension and mild pre-eclampsia at term

Zwangerschapshypertensie en preëclampsie compliceren 6-8% van alle zwangerschappen en vormen in Nederland de belangrijkste oorzaak van maternale morbiditeit en mortaliteit. Vaak is het ziektebeeld mild en treedt op in de aterme periode. Soms ontstaan ernstige complicaties, zoals eclampsie, abruptio placentae of het HELLP-syndroom. Wereldwijd was er tot nu toe geen overeenstemming over het beste beleid bij deze aandoeningen. Inleiding van de baring zou enerzijds maternale complicaties kunnen reduceren, maar anderzijds de kans op een sectio caesarea kunnen verhogen. Het eerste deel van dit proefschrift beschrijft een multicentrisch gerandomiseerde klinische studie (HYPITAT trial (HYpertension and Pre-eclampsia Intervention Trial At Term)), uitgevoerd binnen het Verloskundige Consortium (www.studies-obsgyn.nl/hypitat). Wij onderzochten wat beter is voor vrouwen met een milde zwangerschapsgerelateerde aterme hypertensie: inleiden of afwachten, met het oog op klinische effectiviteit, maternale kwaliteit van leven en kosten. Deze studie werd uitgevoerd in 38 Nederlandse ziekenhuizen. In totaal werden 756 vrouwen gerandomiseerd voor inleiden (n=377) of afwachten (n=379). De resultaten wijzen uit dat inleiden de kans op maternale complicaties verkleint (31% versus 44%; RR 0.71; p<0.001), inleiden een tendens laat zien van minder sectio caesarea (14% versus 19%; RR0.75; p=0.085) en inleiden gemiddeld 831 euro per patiënt goedkoper is dan afwachten. De neonatale uitkomst en de maternale kwaliteit van leven is gelijk tussen beide strategieën. Daarom adviseren wij een inleiding van de baring bij vrouwen met een zwangerschapshypertensie of milde preëclampsie na 37 weken zwangerschap. Het tweede gedeelte van dit proefschrift beschrijft welke factoren een slechte maternale uitkomst bij vrouwen met een aterme zwangerschapshypertensie of milde preëclampsie kunnen voorspellen. Voor deze studies hebben wij gebruik van de HYPITAT database.

Planned early delivery versus expectant management for hypertensive disorders from 34 weeks gestation to term

Cluver, C., et al. 2017. Planned early delivery versus expectant management for hypertensive disorders from 34 weeks gestation to term. Cochrane Database of Systematic Reviews, 1:1-76, Art. CD009273, doi:10.1002/14651858.CD009273.pub2The original publication is available at https://www.cochranelibrary.comBackground: Hypertensive disorders in pregnancy are significant contributors to maternal and perinatal morbidity and mortality. These disorders include well‐controlled chronic hypertension, gestational hypertension (pregnancy‐induced hypertension) and mild pre‐eclampsia. The definitive treatment for these disorders is planned early delivery and the alternative is to manage the pregnancy expectantly if severe uncontrolled hypertension is not present, with close maternal and fetal monitoring. There are benefits and risks associated with both, so it is important to establish the safest option. Objectives: To assess the benefits and risks of a policy of planned early delivery versus a policy of expectant management in pregnant women with hypertensive disorders, at or near term (from 34 weeks onwards). Search methods: We searched Cochrane Pregnancy and Childbirth Trials Register (12 January 2016) and reference lists of retrieved studies. Selection criteria: Randomised trials of a policy of planned early delivery (by induction of labour or by caesarean section) compared with a policy of delayed delivery ("expectant management") for women with hypertensive disorders from 34 weeks' gestation. Cluster‐randomised trials would have been eligible for inclusion in this review, but we found none. Studies using a quasi‐randomised design are not eligible for inclusion in this review. Similarly, studies using a cross‐over design are not eligible for inclusion, because they are not a suitable study design for investigating hypertensive disorders in pregnancy. Data collection and analysis: Two review authors independently assessed eligibility and risks of bias. Two review authors independently extracted data. Data were checked for accuracy. Main results: We included five studies (involving 1819 women) in this review. There was a lower risk of composite maternal mortality and severe morbidity for women randomised to receive planned early delivery (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83, two studies, 1459 women (evidence graded high)). There were no clear differences between subgroups based on our subgroup analysis by gestational age, gestational week or condition. Planned early delivery was associated with lower risk of HELLP syndrome (RR 0.40, 95% CI 0.17 to 0.93, 1628 women; three studies) and severe renal impairment (RR 0.36, 95% CI 0.14 to 0.92, 100 women, one study). There was not enough information to draw any conclusions about the effects on composite infant mortality and severe morbidity. We observed a high level of heterogeneity between the two studies in this analysis (two studies, 1459 infants, I2 = 87%, Tau2 = 0.98), so we did not pool data in meta‐analysis. There were no clear differences between subgroups based on our subgroup analysis by gestational age, gestational week or condition. Planned early delivery was associated with higher levels of respiratory distress syndrome (RR 2.24, 95% CI 1.20 to 4.18, three studies, 1511 infants), and NICU admission (RR 1.65, 95% CI 1.13 to 2.40, four studies, 1585 infants). There was no clear difference between groups for caesarean section (RR 0.91, 95% CI 0.78 to 1.07, 1728 women, four studies, evidence graded moderate), or in the duration of hospital stay for the mother after delivery of the baby (mean difference (MD) ‐0.16 days, 95% CI ‐0.46 to 0.15, two studies, 925 women, evidence graded moderate) or for the baby (MD ‐0.20 days, 95% CI ‐0.57 to 0.17, one study, 756 infants, evidence graded moderate). Two fairly large, well‐designed trials with overall low risk of bias contributed the majority of the evidence. Other studies were at low or unclear risk of bias. No studies attempted to blind participants or clinicians to group allocation, potentially introducing bias as women and staff would have been aware of the intervention and this may have affected aspects of care and decision‐making. The level of evidence was graded high (composite maternal mortality and morbidity), moderate (caesarean section, duration of hospital stay after delivery for mother, and duration of hospital stay after delivery for baby) or low (composite infant mortality and morbidity). Where the evidence was downgraded, it was mostly because the confidence intervals were wide, crossing both the line of no effect and appreciable benefit or harm. Authors' conclusions: For women suffering from hypertensive disorders of pregnancy after 34 weeks, planned early delivery is associated with less composite maternal morbidity and mortality. There is no clear difference in the composite outcome of infant mortality and severe morbidity; however, this is based on limited data (from two trials) assessing all hypertensive disorders as one group. Further studies are needed to look at the different types of hypertensive diseases and the optimal timing of delivery for these conditions. These studies should also include infant and maternal morbidity and mortality outcomes, caesarean section, duration of hospital stay after delivery for mother and duration of hospital stay after delivery for baby. An individual patient meta‐analysis on the data currently available would provide further information on the outcomes of the different types of hypertensive disease encountered in pregnancy.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009273.pub2/fullPublisher's versio

Reduced morbidity by using LigaSure compared to conventional inguinofemoral lymphadenectomy in vulvar cancer patients:A randomized controlled trial

Background: Inguinofemoral lymphadenectomy (IFL) is part of the surgical treatment of different malignancies of the genital tract and/or the lower limb including vulvar carcinoma, penile carcinoma and melanoma. IFL is associated with morbidity in up to 85% of the patients. The aims of this MAMBO-IC study (Morbidity And Measurement of the Body) are to study the feasibility of using LigaSure for IFL and to assess the differences in the incidence of short-term complications using LigaSure versus conventional IFL randomized within each individual patient. Methods: In this multicenter randomized controlled trial (RCT), women diagnosed with squamous cell carcinoma of the vulva with an indication for bilateral IFL were included. It was randomly assigned for which groin the LigaSure was used; the other groin was treated with conventional IFL (sharp/diathermia). We estimated the incidence of >= 1 complication(s) per groin using logistic regression and compared this between the two surgical methods, adjusting for possible confounders. Results: We included 40 groins of 20 patients. The estimated incidence of >= 1 complication(s) was 29% after LigaSure versus 70% after conventional IFL (risk difference 41% (95% CI 19-62), p <0.001). Patients' reported restriction of daily living activities and maximum pain score were equal for both treatment methods. There were no differences in the surgeon reported workload scores. Conclusions: This RCT shows that LigaSure for IFL is feasible and associated with significantly less short-term surgical complications compared to conventional IFL. Further studies with a larger sample size are needed to validate our findings. ISRCTN15057626

Ross River virus disease in two Dutch travellers returning from Australia, February to April 2015

We report two cases of Ross River virus (RRV) infection in Dutch travellers who visited Australia during February to April 2015. These cases coincided with the largest recorded outbreak of RRV disease in Australia since 1996. This report serves to create awareness among physicians to consider travel-related RRV disease in differential diagnosis of patients with fever, arthralgia and/or rash returning from the South Pacific area, and to promote awareness among professionals advising travellers to this region

Orthopoxvirus-specific antibodies wane to undetectable levels 1 year after MVA-BN vaccination of at-risk individuals, the Netherlands, 2022 to 2023

In response to the mpox outbreak in 2022 and 2023, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as JYNNEOS or Imvanex) was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralising antibodies waned to undetectable levels 1 year post vaccination in at-risk individuals who received two doses of MVA-BN administered subcutaneously with an interval of 4 weeks, without prior smallpox or mpox vaccination. Continuous surveillance is essential to understand the impact of declining antibody levels.</p

Clinical and Virological Outcome of Monoclonal Antibody Therapies Across SARS-CoV-2 Variants in 245 Immunocompromised Patients:a multicenter prospective cohort study

Background. Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants. Methods. In this multicenter prospective cohort study, we enrolled B-cell- and/or T-cell-deficient patients treated with casirivimab/imdevimab, sotrovimab, or tixagevimab/cilgavimab. SARS-CoV-2 RNA was quantified and sequenced weekly, and time to viral clearance, viral genome mutations, hospitalization, and death rates were registered. Results. Two hundred and forty five patients infected with the Delta (50%) or Omicron BA.1, 2, or 5 (50%) variant were enrolled. Sixty-seven percent were vaccinated; 78 treated as outpatients, of whom 2 required hospital admission, but both survived. Of the 159 patients hospitalized at time of treatment, 43 (27%) required mechanical ventilation or died. The median time to viral clearance was 14 days (interquartile range, 7-22); however, it took &gt;30 days in 15%. Resistance-associated spike mutations emerged in 9 patients in whom the median time to viral clearance was 63 days (95% confidence interval, 57-69; P &lt; .001). Spike mutations were observed in 1 of 42 (2.4%) patients after treatment with 2 active mAbs, in 5 of 34 (14.7%) treated with actual monotherapy (sotrovimab), and 3 of 20 (12%) treated with functional monotherapy (ie, tixagevimab/cilgavimab against tixagevimab-resistant variant). Conclusions. Despite treatment with mAbs, morbidity and mortality of COVID-19 in ICPs remained substantial. Combination antiviral therapy should be further explored and may be preferred in severely ICPs.</p

Scenarios of future mpox outbreaks among men who have sex with men:a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022

Background: Following the 2022–2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks. Aim: We combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM). Methods: Serum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.Results: The seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks. Conclusion: Our findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.</p

An evaluation of serological methods to diagnose tick-borne encephalitis from serum and cerebrospinal fluid

Background: Tick-borne encephalitis (TBE) is an infectious disease endemic to large parts of Europe and Asia. Diagnosing TBE often relies on the detection of TBEV-specific antibodies in serum and cerebrospinal fluid (CSF) as viral genome is mostly not detectable once neurological symptoms occur. Objectives: We evaluated the performance of TBEV IgM and IgG ELISAs in both serum and CSF of confirmed TBEV patients and discuss the role of (CSF) serology in TBEV diagnostics. Study design: For the assay evaluation we collected specimen from confirmed TBEV patients. Assay specificity was assessed using sera from patients with a related flavivirus infection or other acute infection. A selected ELISA assay was used to analyze TBEV-specific antibodies in CSF and to evaluate the use in confirming TBE diagnosis. Results: In this study the overall sensitivity of the IgM TBEV ELISAs was acceptable (94 -100 %). Four out of five IgM ELISA's demonstrated an excellent overall specificity from 94 -100% whereas a low overall specificity was observed for the IgG TBEV ELISAs (30-71%). Intrathecal antibody production against TBEV was demonstrated in a subset of TBE patients. Conclusions: In four out of five ELISAs, IgM testing in serum and CSF of TBE patients is specific and confirmative. The lack of IgG specificity in all ELISAs emphasizes the need of confirmatory testing by virus neutralisation, depending on the patient's background and the geographic location of exposure to TBEV. A CSF-serum IgG antibody index can support the diagnosis specifically in chronic disease or once IgM has disappeared

Zika virus infection and Guillain-Barré syndrome in three patients from Suriname

We present three patients from Suriname who were diagnosed with Guillain-Barré syndrome (GBS) during the Zika virus (ZIKV) outbreak in this country. One patient had a positive ZIKV urine real-time RT-PCR (qRT-PCR) result. The other two patients had a negative ZIKV urine qRT-PCR but a positive virus neutralization test and presence of IgG antibodies against ZIKV in the serum. Considering the evidence of a past ZIKV infection and absence of evidence for recent infections with the most common preceding infections of GBS, it is very likely that these GBS cases were triggered by ZIKV