Assessing Endovascular Aneurysm Repair Suitability According to Graft-Specific Instructions for Use in Patients With a Ruptured Abdominal Aortic Aneurysm.

PURPOSE: The purpose of the study is to ascertain endovascular aneurysm repair (EVAR) suitability in relation to stent-graft-specific instructions for use (IFU) in patients with a ruptured abdominal aortic aneurysm (RAAA). MATERIALS AND METHODS: Using the preoperative computed tomography angiography (CTA), the aortic morphology of patients undergoing surgical repair of a RAAA in 2 Dutch hospitals between January 2014 and December 2019 was retrospectively assessed. Three-dimensional and central luminal line reconstructions were used. Anatomical suitability was defined according to the IFU of the stent graft system used. RESULTS: Of 128 included patients, 112 (88%) were men and the mean age was 74.1 (SD=7.6) years. Anatomy within IFU for EVAR was present in 31 patients (24%). Overall, 94 patients (73%) were treated with open surgical repair (OSR) and 34 patients (27%) were treated with EVAR. Anatomy within IFU was present in 15 OSR patients (16%) and 16 EVAR patients (47%). In patients with anatomy outside of IFU, 90% (87/97) had unsuitable neck anatomy and 64% (62/97) had insufficient neck length. An unsuitable distal iliac landing zone was observed in 35 patients. Perioperative mortality was 27% (34/128), with no difference between OSR and EVAR (25/94 vs 9/34; p=0.989). CONCLUSION: Most RAAA patients in this series did not have aortic anatomy within IFU for EVAR, mainly due to insufficient neck length. However, whether anatomy outside of IFU equates to unsuitability for EVAR in an emergency setting remains a matter of debate and warrants further research. CLINICAL IMPACT: The treatment of a ruptured abdominal aortic aneurysm can consist of endovascular repair or open repair. Retrospective anatomical assessment shows that most patients do not have anatomy inside the instructions for use for endovascular aneurysm repair, mainly due to insufficient neck length. Whether anatomy outside the instructions for use equates unsuitability for endovascular aneurysm repair remains a matter of debate.

Multicomponent Prehabilitation as a Novel Strategy for Preventing Delirium in Older Chronic Limb Threatening Ischemia Patients: A Study Protocol.

Objective: Chronic limb threatening ischemia is the final stage of peripheral arterial disease. Current treatment is based on revascularization to preserve the leg. In the older, hospitalized chronic limb threatening ischemia patient, delirium is a frequent and severe complication after revascularization. Delirium leads to an increased length of hospital stay, a higher mortality rate and a decrease in quality of life. Currently, no specific guidelines to prevent delirium in chronic limb threatening ischemia patients exist. We aim to evaluate the effect of a multicomponent, multidisciplinary prehabilitation program on the incidence of delirium in chronic limb threatening ischemia patients ≥65 years. Design: A prospective observational cohort study to investigate the effects of the program on the incidence of delirium will be performed in a large teaching hospital in the Netherlands. This manuscript describes the design of the study and the content of this specific prehabilitation program. Methods: Chronic limb threatening ischemia patients ≥65 years that require revascularization will participate in the program. This program focuses on optimizing the patient's overall health and includes delirium risk assessment, nutritional optimization, home-based physical therapy, iron infusion in case of anaemia and a comprehensive geriatric assessment in case of frailty. The primary outcome is the incidence of delirium. Secondary outcomes include quality of life, amputation-free survival, length of hospital stay and mortality. Exclusion criteria are the requirement of acute treatment or patients who are mentally incompetent to understand the procedures of the study or to complete questionnaires. A historical cohort from the same hospital is used as a control group. Discussion: This study will clarify the effect of a prehabilitation program on delirium incidence in chronic limb threatening ischemia patients. New insights will be obtained on optimizing a patient's preoperative mental and physical condition to prevent postoperative complications, including delirium. Trial: This protocol is registered at the Netherlands National Trial Register (NTR) number: NL9380.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Effect of conservative treatment in aortoiliac occlusive disease.

Objective: To determine the effect of primary conservative treatment without revascularization in patients with proven aortoiliac occlusive disease (AIOD) presenting with intermittent claudication (IC).Background: The initial treatment of IC should focus on supervised exercise therapy (SET) and pharmacotherapy. Nowadays, primary endovascular revascularization (EVR) has become increasingly popular in patients with all types of AIOD. But in daily practice, EVR is often performed without initially extensive exercise.Method: This is a single centre retrospective study from December 2012 to September 2017. Primary outcomes were maximum walking distance (MWD) and patient satisfaction. Secondary outcomes were revascularization rate and mortality.Results: Twenty-four patients were included. Mean age was 64 years (SD: 9). Mean follow-up was 28 months (SD: 17). Nineteen patients (80%) had SET. In 18 (75%) patients, the MWD was improved compared to the initial situation. In five (21%) patients, the MWD stayed the same. The MWD of one (4%) patient decreased. Overall satisfaction rate was 87%. Three patients (13%) were not satisfied with the conservative treatment and eventually got an EVR. There was no disease related death.Conclusions: Conservative treatment, especially with SET, has acceptable subjective symptom outcomes in selected patients with AIOD. It could be a good alternative treatment for certain patients with AIOD and IC.

The Role of Delirium and Other Risk Factors on Mortality in Elderly Patients with Critical Limb Ischemia Undergoing Major Lower Limb Amputation.

BACKGROUND: Delirium in patients with critical limb ischemia (CLI) is associated with increased mortality. The main goal of this study was to investigate the association between delirium and mortality in patients undergoing major lower limb amputation for CLI. In addition, other risk factors associated with mortality were analyzed. METHODS: An observational cohort study was conducted including all patients aged ≥70 years with CLI undergoing a major lower limb amputation between January 2014 and July 2017. Delirium was scored using the Delirium Observation Screening Score in combination with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Risk factors for mortality were analyzed by calculating hazard ratios using a Cox proportional hazards model. RESULTS: In total, 95 patients were included; of which, 29 (31%) patients developed a delirium during admission. Delirium was not associated with an increased risk of mortality (hazard ratio [HR] = 0.84; 95 % confidence interval [CI]: 0.51-1.73; P = 0.84). Variables independently associated with an increased risk of mortality were age (HR 1.1; 95% CI 1.0-1.1), cardiac history (HR 3.3; 95% CI 1.8-6.1), current smoking (HR 2.9; 95% CI 1.6-5.5), preoperative anemia (HR 2.8; 95% CI 1.1-7.2), and living in a nursing home (HR 2.2; 95% CI 1.1-4.4). CONCLUSION: Delirium was not associated with an increased mortality risk in elderly patients with CLI undergoing a major lower limb amputation. Factors related to an increased mortality risk were age, cardiac history, current smoking, preoperative anemia, and living in a nursing home.

Surgical Site and Graft Infections in Endovascular and Open Abdominal Aortic Aneurysm Surgery.

BACKGROUND: Surgical site infections (SSIs) constitute one of many major complications after aortic aneurysm surgery and its details and outcome have not been evaluated extensively. This research evaluates the incidence and outcome of SSI and graft infection in open and endovascular abdominal aortic aneurysm surgery. PATIENTS AND METHODS: A retrospective study was performed, including all patients who underwent surgery for aortoiliac aneurysmatic disease between January 2000 and December 2016 in the Amphia Hospital, Breda, The Netherlands. Surgical site infections were defined in accordance with criteria of the U.S. Centers for Disease Control and Prevention (CDC). Aortic graft infection was diagnosed by a combination of computed tomography imaging and microbiologic results. RESULTS: Between January 2000 and December 2016, 845 patients (mean age, 72.80 ± 7.15 y, 86.3% male) underwent abdominal aneurysm surgery (477 endovascular, 368 open). The total SSI rate was 3.1% (12 endovascular [2.5%], 14 open [3.8%], p = 0.318) with 0.8% deep SSI (26.9% of SSIs). No difference in SSIs was found between acute and elective surgery (2.9% vs. 3.1%, p = 1.000). Patients with SSI had a longer duration of stay (mean, 27.65 ± 30.74 d vs. 9.79 ± 12.50 d, p < 0.0001) but no difference in 30-day or 1-year mortality. Twenty-four graft infections occurred (4.3% of open vs. 1.7% of endovascular surgery, p = 0.023) of which 20 (83.3%) required surgery. Two-year mortality was higher when graft infections occurred (33.3% vs. 16.3%, p = 0.046). Surgical site infections (odds ratio [OR] 7.10, 95% [CI] 2.10-23.98) and mycotic aneurysms (OR 9.38, 95% CI 1.78-54.19) are independent determinants for graft infections. CONCLUSION: This study shows that SSIs after endovascular aortic surgery are as common as after open aortic surgery. Furthermore, this study supports the concept that aortic graft infection is highly associated with SSIs and mycotic aneurysms. Studies evaluating the prevention or early diagnosis of graft infection after SSIs through intensified imaging follow-up or even long-term antibiotic treatment should be considered.

Increased glucocerebrosidase expression and activity in preeclamptic placenta.

INTRODUCTION: Lysosomal glucosidase beta acid (GBA) deficiency is inherent to Gaucher disease, Parkinsonism and Lewy-body dementia. Increased GBA expression has never been associated with human disease. We describe increased GBA expression and activity in placenta from preeclamptic pregnancies. METHODS: 112 placenta biopsies were available for qPCR, analysis of GBA gene expression and activity. Microanalysis was performed on 20 placenta samples. Alternatively spliced placental GBA transcripts were cloned, expressed in HEK293 cells and analyzed by Western blot and activity assay. RESULTS: GBA is expressed in the syncytiotrophoblast layer of human placenta already at 5 weeks of gestation. We identified five novel GBA transcripts in placenta that enzymatically inactive when expressed in HEK293 cells. Both GBA RNA expression and enzymatic activity are upregulated in preeclamptic placenta. Microarray analysis of 20 placenta tissues identified 158 genes co-regulating with GBA expression and gene enrichment analysis highlights lysosomal function. In our micro-array data GBA expression does not correlate with FLT1 expression, currently the most powerful marker for preeclampsia. There are 89 transcripts that are negatively correlated with GBA expression of which BMP4 and TFEB are interesting as they are essential to early placenta function. DISCUSSION: Although very speculative, we hypothesize that increased GBA expression might relate to placentation through decreased BMP4 signaling or vascularization through downregulation of TFEB. Ceramide, the product of hydrolysis of glucosylceramide by GBA and involved in the regulation of cell differentiation, survival and apoptosis, is another putative candidate linking increased GBA activity to preeclampsia. Both pathways merit further investigation.

Renal function 5 years after open and endovascular aortic aneurysm repair from a randomized trial.

BACKGROUND: Deterioration of renal function after major vascular surgery is an important complication, and may vary between patients undergoing endovascular (EVAR) or open surgical (OR) repair of an abdominal aortic aneurysm (AAA). The objective was to determine the impact of OR and EVAR on renal function after 5 years. METHODS: This was a post hoc analysis of data collected prospectively from the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial. Five years after surgery, creatinine levels were available for 189 patients (94 after OR and 95 after EVAR). The severity of renal disease was staged using the chronic kidney disease classification of the US National Kidney Foundation clinical guidelines. RESULTS: Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the estimated glomerular filtration rate (eGFR) for the entire group declined over time, with a mean(s.d.) preoperative value of 80·0(7·6) ml per min per 1·73 m(2) compared with 75·7(9·7) ml per min per 1·73 m(2) after 5 years (mean difference 4·2 (95 per cent confidence interval 3·2 to 5·3) ml per min per 1·73 m(2) ; P < 0·001). Five years after surgery, the mean eGFR (CKD-EPI equation) was not significantly different between the OR and EVAR groups: 76·3(9·3) versus 75·1(10·0) ml per min per 1·73 m(2) (mean difference 1·2 (-1·6 to 3·9) ml per min per 1·73 m(2) ; P = 0·410). CONCLUSION: Renal function 5 years after OR and EVAR for AAA was similar. Neither surgical procedure accelerated the loss of renal function.

Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa is a chronic, recurrent, suppurative cutaneous disease. Despite its incidence, optimal medical or surgical treatment remains unclear. This review describes the disease, ranging from pathogenesis to treatment and prognosis. METHODS: Articles were sourced from PubMed and Medline, using the MeSH terms 'hidradenitis suppurativa' and 'acne inversa'. Selection of articles was based on peer review, journal, relevance and English language. RESULTS AND CONCLUSION: On the basis of histological findings, the disease is now considered inflammatory and originating from the hair follicle; therefore, the term 'acne inversa' is favoured by some experts. The exact aetiology remains obscure but smoking seems to be a major triggering factor. Treatment should be individualized according to the site and extent of the disease. Absolute cessation of smoking is essential in the treatment of hidradenitis. Management with antibiotics or other medications may relieve early symptoms, but radical surgery may be necessary for control and to prevent recurrence.

Seven placental transcripts characterize HELLP-syndrome.

The human placenta is prerequisite for the development of gestational hypertensive diseases like early-onset preeclampsia (PE) and Hemolysis, Elevated Liver enzymes and Low platelets (HELLP) syndrome. Both syndromes are associated with extensive maternal and perinatal mortality, and morbidity with life long consequences. We aimed to investigate differences in gene expression between placental tissue obtained from normotensive pregnant women and women with PE and HELLP syndrome. Firstly, comparison of Serial Analysis of Gene Expression profiles of 28 weeks' control placenta (available after idiopathic premature delivery) to a HELLP/PE placenta matched for gestational age identified 404 differentially expressed transcripts. Secondly, using sqPCR, the expression levels of 37 of these transcripts were analyzed in placentas of 36 pregnant women, 22 with preeclampsia and HELLP syndrome. Thirdly, nearest centroid classification determined the HELLP specific molecular signature consisting of the upregulated expression of genes encoding the vascular endothelial growth factor receptor (FLT1), leptin (LEP), pappalysin 2 (PAPPA2), and WW domain containing transcription regulator 1 (WWTR1) combined with down regulated expression of the genes encoding cadherin-associated protein (CTNNAL), glutathione S-transferase pi (GSTP1) and calgranulin A (S100A8). This set discriminates HELLP placenta from control and PE placenta with a 24% misclassification rate (95% CI 8.3-41.9%), independent from known risk factors like parity and ethnicity. The transcripts involved correspond to diverse molecular pathways, exemplifying the multigenic molecular basis of the disorder. This distinct placental molecular signature suggests that HELLP is not a PE variant but a separate disease entity. Our data may prove fundamental for the further molecular analysis of PE and HELLP syndrome.

Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

Evaluation of hepatitis C antibody testing in saliva specimens collected by two different systems in comparison with HCV antibody and HCV RNA in serum.

Two different ELISA assays, the Ortho HCV 3.0 ELISA (Ortho Diagnostics Systems) and the Mono-Lisa anti-HCV Plus (Sanofi Diagnostics Pasteur) were evaluated for the detection of hepatitis C virus (HCV) antibody in saliva samples. Specimens were collected from 152 individuals who participated in a longitudinal cohort study on HIV infection, and who used illicit drugs. Saliva specimens were collected using two different systems: Salivette (Sarstedt) and Omni-Sal (Saliva Diagnostic Systems). Saliva specimens were tested following modified protocols by both ELISAs, and the results were compared with serum specimens that were tested according to the instructions of the manufacturer. Serum samples of 102 (67%) participants were positive by both assays, and 50 persons were negative for HCV antibody. A total of 99 of the 102 serum specimens were confirmed as positive using Ortho Riba HCV 3.0 (Ortho Diagnostics System) and Deciscan HCV (Sanofi Diagnostics Pasteur), and 3 yielded discrepant results. As no cut-off level is known for testing saliva samples by ELISA, 3 different levels were chosen: mean (M) + 1 standard deviation (SD), M + 2 SD, and M + 3 SD of the optical densities of saliva tests of the 50 HCV serum antibody negative persons. At a level of M + 1 SD and M + 2 SD the Salivette/Mono-Lisa combination gave the greatest proportion of HCV antibody positive saliva specimens obtained from the 102 HCV serum antibody positive participants, 88% and 79%, respectively. Differences between the various collection systems and assay combinations were not significant statistically. In 76 of the 102 persons with HCV antibodies in serum, HCV RNA was detected in serum. Salivary presence of HCV RNA, however, could not be demonstrated. The results show that the assays compared are unsuitable for diagnostic use, but the sensitivities of the assays are acceptable for use in epidemiological studies.

Comparison between the LCx Probe system and the COBAS AMPLICOR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in patients attending a clinic for treatment of sexually transmitted diseases in Amsterdam, The Netherlands.

Two assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae were compared: the LCx Probe system (the LCx system; Abbott Diagnostic Laboratories, North Chicago, Ill.) and the COBAS AMPLICOR C. trachomatis/N. gonorrhoeae system (the COBAS AMPLICOR system; Roche Diagnostic Systems, Branchburg, N.J.). Endocervical swab specimens, male urethral swab specimens, and female and male urine specimens were collected from 503 female and 498 male visitors attending a sexually transmitted diseases clinic in Amsterdam, The Netherlands. Prevalences for C. trachomatis were 12.5% (63 of 503) and 10.0% (50 of 498) in females and males, respectively. The prevalences for N. gonorrhoeae were 1.2% (6 of 503) and 4.2% (21 of 498) in females and males, respectively. Both assays showed high values for sensitivity and specificity with regard to the detection of C. trachomatis in endocervical swab specimens, male urethral swab specimens, and female and male urine specimens. The sensitivities for the LCx system were 92.1, 90.0, 88.9, and 94.0% for each type of specimen, respectively; and the sensitivies for the COBAS AMPLICOR system were 96.8, 98.0, 82.5, and 92.0% for each type of specimen, respectively. Specificities ranged between 98.4 and 100%. The sensitivity of the LCx system for the detection of N. gonorrhoeae was 100% for female cervical swab and urine specimens and male urethral swab specimens, while for male urine specimens the sensitivity was 95.2%; the specificity was 100% for all types of specimens. For the detection of N. gonorrhoeae by the COBAS AMPLICOR assay, the sensitivity for female cervical swab and male urethral swab specimens was 100%, that for female urine specimens was 66.7%, and that for male urine specimens was 95.2%. However, the predictive values of a positive test for female cervical swab specimens and urine specimens were 31.6 and 36.4%, respectively. Sequence analysis of the amplimers obtained by an in-house 16S rRNA PCR of the solely COBAS AMPLICOR system-positive swab specimens revealed neither N. gonorrhoeae nor other Neisseria spp. The COBAS AMPLICOR assay was considered not suitable for screening for infections with N. gonorrhoeae. If this assay is used for detection of N. gonorrhoeae, confirmation of positive results by a reliable test is mandatory.

Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam, The Netherlands.

The most common etiologic agents of genital ulcer disease (GUD) are herpes simplex virus type 1 (HSV-1), HSV-2, Treponema pallidum, and Haemophilus ducreyi. In an outpatient clinic for sexually transmitted diseases in Amsterdam, The Netherlands, specimens from 372 patients with GUD were collected from February to November 1996. Sera were collected at the time of the symptoms and, for most patients, also during follow-up visits. Swabs in viral transport medium were used for HSV culture and for detection of DNA. The most prevalent pathogen found was HSV-2, which was detected by culture in 35% of the patients and by PCR in 48% of the patients. Also, HSV-1 infection was more often detected by PCR (7.8%) than by culture (5.6%). Evidence for an active infection with T. pallidum was found in 1.9% of the patients, using serological tests. A multiplex PCR for simultaneous T. pallidum and H. ducreyi DNA detection was positive for T. pallidum in 3.3% of the samples and for H. ducreyi in only 0.9% (3 out of 368) of the samples. The sensitivity of the PCR was superior to that of culture for HSV detection and to that of serology for T. pallidum detection. Specific H. ducreyi immunoglobulin G antibodies were detected in sera of 5.2% of the patients, with no concordance between serology and PCR. In 37% of the cases, none of the tested microorganisms was detected. Performance of PCR in addition to conventional techniques significantly improved the diagnosis of GUD.

Comparison of a monoclonal antibody-blocking enzyme-linked immunoassay and a strip immunoblot assay for identifying type-specific herpes simplex virus type 2 serological responses.

Detection of herpes simplex virus type 2 (HSV-2)-specific antibodies by a monoclonal antibody (MAb)-blocking enzyme-linked immunoassay (EIA) was compared with detection by a strip immunoblot assay (SIA) in a sexually transmitted disease (STD) clinic population. The study population consisted of 1,683 genitourinary medicine clinic attendees (582 women and 1,101 men). Sera were tested for the presence of HSV-2 antibody by use of the blocking EIA, in which binding of the MAb AP-1 to HSV-2 glycoprotein G-2 (gG-2) is blocked by HSV-2-specific antibody. The Chiron RIBA HSV-1 and -2 strip immunoassay (SIA) utilizes HSV-1- and HSV-2-specific or cross-reactive antigens immobilized on nitrocellulose strips (HSV gB-1 and HSV gG-1 peptide bands specific for HSV-1 antibody, HSV-2 gG-2 band specific for HSV-2 antibody, and HSV gD-2 band cross-reactive for HSV-1 and HSV-2 antibodies). A total of 1,612 sera were tested by MAb-blocking EIA for HSV-2 antibody and by SIA for HSV-1 and HSV-2 antibodies. By EIA, 541 (33.6%) sera were positive for HSV-2 antibody and 1,068 sera were negative for HSV-2 antibody; 3 sera gave equivocal results. HSV-2 antibody was detected in 555 (34.4%) sera by SIA; 144 (26%) of these sera possessed only HSV-2 antibody, and 411 (74%) sera contained both HSV-1 and HSV-2 antibodies. SIA detected HSV-1 antibody in 1,155 (71.6%) sera; 744 (64%) of these sera contained HSV-1 antibody alone. Sixteen sera contained antibody against HSV but could not be typed by SIA. A total of 512 sera were positive for HSV-2 antibody by both the EIA and SIA. We concluded that the blocking EIA and SIA showed a high level of agreement in detecting HSV-2 antibody in this population. In contrast to the SIA, the blocking EIA is a useful tool for large epidemiological studies, though the SIA proved to be slightly more sensitive once sera with discrepant results were further tested.

Two trials of antenatal thyrotrophin-releasing hormone for fetal maturation: stopping before the due date. Antenatal TRH Trial and the Thyroneth Trial Groups.

OBJECTIVES: To determine whether the addition of antenatal thyrotrophin-releasing hormone (TRH) to corticosteroids, given to women at risk of preterm delivery, would decrease the risk of death and severe morbidity associated with prematurity. DESIGN: Two concurrent multicentre, double blind, randomised, placebo-controlled trials were designed with a common core dataset to be analysed as a single large pragmatic trial. SETTING: Hospital maternity units. POPULATIONS: Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation. INTERVENTIONS: Antenatal administration of TRH 400 microg every eight hours for four doses versus matching placebo. MAIN OUTCOME MEASURES: Primary: death of the baby or chronic lung disease (defined as oxygen dependency at 28 days after birth). Secondary: other measures of respiratory morbidity, in particular respiratory distress syndrome. Other measures of short term neonatal morbidity including intraventricular haemorrhage and necrotising enterocolitis. Measures of maternal side effects. RESULTS: The antenatal TRH trial was halted early on the basis of external evidence. Overall a total of 225 women were recruited who delivered 275 babies. The primary outcome of death or chronic lung disease occurred in 33 babies in the TRH group and 43 babies in the placebo group (RR 0.8, 95% CI 0.5-1.2). There were no other differences between the two groups. Stratified analysis did not reveal any differences between the two groups depending on how long before the time of delivery the mother had received the TRH or placebo. CONCLUSIONS: These trials are too small to provide convincing evidence of the effect of antenatal TRH on neonatal outcome. When added to the existing systematic review and meta-analysis, however, these data should provide evidence on which subsequent practice can be based. The process by which the trials were monitored and stopped is of relevance to future trials.

[Opportunistic screening for genital infections with Chlamydia trachomatis among the sexually active population of Amsterdam. Il Over 90% participation and almost 5% prevalence]. / Opportunistische screening op genitale infecties met Chlamydia trachomatis onder de seksueel actieve bevolking in Amsterdam. I. Meer dan 90% deelname en bijna 5% prevalentie.

OBJECTIVE: To determine in an opportunistic screening programme for Chlamydia trachomatis (CT) the participation and the CT prevalence among the heterosexual population. METHODS: Heterosexually active men and women, 15-40 years old, who consulted a general practitioner in Amsterdam, the Netherlands, in the period May 1996-April 1997, without symptoms of a sexually transmitted disease, were asked after informed consent had been given to provide a first-voided urine sample and a few sociodemographic data. The urine was investigated for CT by means of a ligase chain reaction. In case of a CT infection, the general practitioner was asked for information on treatment and partner notification. RESULTS: A total of 3689 persons were eligible for the study of whom 214 (5.8%) refused participation. Men refused more often than women (9.0% and 4.3% respectively). No relation was found with ethnic background or health care insurance (national health cost insurance/private medical insurance). Refusers were somewhat younger than participants (not statistically significant). CT was diagnosed in 4.9% (95% confidence interval (95% CI): 4.1-5.9) of the women and in 4.7% (95% CI: 3.6-6.1) of the men. In women a decreasing trend was seen in the prevalence of CT with an increase in age: from 13.4% in the group 15-19 years old to 2.3% in the group 35-40 years old. Independent of age a higher prevalence was found in Surinam Creole women. In 83% of the CT patients the general practitioner spoke with the patient about partner notification; usually there was one partner. CONCLUSION: There was a high participation rate (94%) in this opportunistic screening programme in which urine was tested for presence of CT. The CT prevalence in this asymptomatic population was almost 5%, but it was significantly higher in young women and women from Surinam. It is proposed to start such a screening programme in all general practices in Amsterdam.

Evaluation of an expanded two-ELISA approach for confirmation of reactive serum samples in an HIV-screening programme for pregnant women.

Serum specimens were collected from 31,232 pregnant women in Amsterdam between 1988 and 1995 in a screening programme for human deficiency virus (HIV) infection. The sera of 56 (0.179%) women tested were confirmed as positive for HIV. A total of 67 sera reacted positive or borderline by the screening enzyme-linked immunosorbent assay (ELISA) and indeterminate or negative by HIV-1 Western blot; 42 of these specimens were available for evaluation of the strategy for diagnosis of HIV infection. A two-ELISA approach with the second ELISA based on a principle different from that of the screening ELISA, expanded with the use of a membrane immunoassay based on two synthetic peptides specific for HIV-1 gp41 and HIV-2 gp36 envelope proteins, was compared with the Western blot analysis. Indeterminate results were resolved with a nucleic acid sequence-based amplification assay (NASBA) for HIV-1 RNA and a strip immunoassay (SIA) for the simultaneous detection of antibodies to HIV-1 or HIV-2 and HIV-1 p24 antigen. Eleven samples were weakly or borderline positive by the screening test and gave indeterminate results by Western blot. The expanded two-ELISA approach designated these sera as HIV-negative, and confirmed negative by NASBA and the SIA. Twenty-one samples showed borderline or positive results on the screening test and negative results by Western blot. Again, these sera were characterised as HIV-negative by the expanded two-ELISA procedure, and this characterisation was confirmed by both NASBA and the SIA. Five HIV-2-positive serum samples were recognised by the expanded two-ELISA approach and the SIA; these sera were negative by NASBA. Finally, another five serum samples were weakly or borderline positive by both ELISAs and positive by the membrane immunoassay; of these five, two sera generated positive patterns and the other three indeterminate patterns on Western blots, and four were positive by the NASBA assay. Follow-up serum specimens from these five women were negative and the reactivity of the initial specimens was thus likely to have been the result of cross-contamination. Our results demonstrate the effectiveness of a simple confirmation approach of two HIV ELISAs expanded with a membrane spot assay to discriminate between infection with HIV-1 or HIV-2. The data also indicate the importance of retesting individuals with indeterminate or positive confirmational results to exclude the possibility of contamination as the cause of reactivity of the original specimen.