Low thrombin generation in postmenopausal women using estetrol.

OBJECTIVE: Estetrol (E4) represents a novel estrogen of interest to relieve vasomotor symptoms. E4 activates the nuclear estrogen receptor α (ERα) but antagonizes the estradiol ERα-dependent membrane-initiated steroid signaling pathway. The distinct pharmacological properties of E4 could explain its low impact on hemostasis. This study aimed to assess the effect of E4 on coagulation in postmenopausal women, using the thrombin generation assay (TGA). METHODS: Data were collected from a multicenter, randomized, placebo-controlled, dose-finding study in postmenopausal women (NCT02834312). Oral E4 (2.5 mg, n = 42; 5 mg, n = 29; 10 mg, n = 34; or 15 mg, n = 32) or placebo (n = 31) was administered daily for 12 weeks. Thrombograms and TGA parameters were extracted for each subject at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, all treatment groups showed a mean thrombogram (±95% confidence interval [CI] of the mean) within the reference ranges, that is, the 2.5th-97.5th percentile of all baseline thrombograms (n = 168), as well as for TGA parameters. CONCLUSIONS: The intake of E4 15 mg for 12 weeks led to significant but not clinically relevant changes compared to baseline as the mean values (±95% CI of the mean) remained within reference ranges, demonstrating a neutral profile of this estrogen on hemostasis.

Five-Year Follow-Up of a Slowly Resorbable Biosynthetic P4HB Mesh (Phasix) in VHWG Grade 3 Incisional Hernia Repair.

Objective: To assess the 5-year recurrence rate of incisional hernia repair in Ventral Hernia Working Group (VHWG) 3 hernia with a slowly resorbable mesh. Summary Background Data: Incisional hernia recurs frequently after initial repair. In potentially contaminated hernia, recurrences rise to 40%. Recently, the biosynthetic Phasix mesh has been developed that is resorbed in 12-18 months. Resorbable meshes might be a solution for incisional hernia repair to decrease short- and long-term (mesh) complications. However, long-term outcomes after resorption are scarce. Methods: Patients with VHWG grade 3 incisional midline hernia, who participated in the Phasix trial (Clinilcaltrials.gov: NCT02720042) were included by means of physical examination and computed tomography (CT). Primary outcome was hernia recurrence; secondary outcomes comprised of long-term mesh complications, reoperations, and abdominal wall pain [visual analogue score (VAS): 0-10]. Results: In total, 61/84 (72.6%) patients were seen. Median follow-up time was 60.0 [interquartile range (IQR): 55-64] months. CT scan was made in 39 patients (68.4%). A recurrence rate of 15.9% (95% confidence interval: 6.9-24.8) was calculated after 5 years. Four new recurrences (6.6%) were found between 2 and 5 years. Two were asymptomatic. In total, 13/84 recurrences were found. No long-term mesh complications and/or interventions occurred. VAS scores were 0 (IQR: 0-2). Conclusions: Hernia repair with Phasix mesh in high-risk patients (VHWG 3, body mass index >28) demonstrated a recurrence rate of 15.9%, low pain scores, no mesh-related complications or reoperations for chronic pain between the 2- and 5-year follow-up. Four new recurrences occurred, 2 were asymptomatic. The poly-4-hydroxybutyrate mesh is a safe mesh for hernia repair in VHWG 3 patients, which avoids long-term mesh complications like pain and mesh infection.

The daily updated Dutch national database on COVID-19 epidemiology, vaccination and sewage surveillance.

The Dutch national open database on COVID-19 has been incrementally expanded since its start on 30 April 2020 and now includes datasets on symptoms, tests performed, individual-level positive cases and deaths, cases and deaths among vulnerable populations, settings of transmission, hospital and ICU admissions, SARS-CoV-2 variants, viral loads in sewage, vaccinations and the effective reproduction number. This data is collected by municipal health services, laboratories, hospitals, sewage treatment plants, vaccination providers and citizens and is cleaned, analysed and published, mostly daily, by the National Institute for Public Health and the Environment (RIVM) in the Netherlands, using automated scripts. Because these datasets cover the key aspects of the pandemic and are available at detailed geographical level, they are essential to gain a thorough understanding of the past and current COVID-19 epidemiology in the Netherlands. Future purposes of these datasets include country-level comparative analysis on the effect of non-pharmaceutical interventions against COVID-19 in different contexts, such as different cultural values or levels of socio-economic disparity, and studies on COVID-19 and weather factors.

Slowly resorbable biosynthetic mesh: 2-year results in VHWG grade 3 hernia repair.

INTRODUCTION: Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months. METHODS: A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm2, scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months. RESULTS: Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery. CONCLUSION: After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations. TRIAL REGISTRATION: Registered on clinicaltrials.gov (NCT02720042), March 25, 2016.

Implementing preoperative Botulinum toxin A and progressive pneumoperitoneum through the use of an algorithm in giant ventral hernia repair.

BACKGROUND: Repair of large ventral hernias with loss of domain can be facilitated by preoperative Botulinum toxin A (BTA) injections and preoperative progressive pneumoperitoneum (PPP). The aim of this study is to evaluate the outcomes of ventral hernioplasty using a standardized algorithm, including component separation techniques, preoperative BTA and PPP. METHODS: All patients between June 2014 and August 2018 with giant hernias (either primary or incisional) of more than 12 cm width were treated according to a previously developed standardized algorithm. Retrospective data analysis from a prospectively collected dataset was performed. The primary outcome was closure of the anterior fascia. Secondary outcomes included complications related to the preoperative treatment, postoperative complications, and recurrences. RESULTS: Twenty-three patients were included. Median age was 65 years (range 28-77) and median BMI was 31.4 (range 22.7-38.0 kg/m2). The median loss of domain was 29% (range 12-226%). For the primary and secondary endpoints, 22 patients were analyzed. Primary closure of the anterior fascia was possible in 82% of all patients. After a median follow-up of 19.5 months (range 10-60 months), 3 patients (14%) developed a hernia recurrence and 16 patients (73%) developed 23 surgical site occurrences, most of which were surgical site infections (54.5%). CONCLUSION: Our algorithm using both anterior or posterior component separation, together with preoperative BTA injections and PPP, achieved an acceptable fascial closure rate. Further studies are needed to explore the individual potential of BTA injections and PPP, and to research whether these methods can prevent the need for component separation, as postoperative wound morbidity remains high in our study.

Conservative treatment versus elective repair of umbilical hernia in patients with liver cirrhosis and ascites: results of a randomized controlled trial (CRUCIAL trial).

PURPOSE: To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. METHODS: Patients with an umbilical hernia and liver cirrhosis and ascites were randomly assigned to receive either elective repair or conservative treatment. The primary endpoint was overall morbidity related to the umbilical hernia or its treatment after 24 months of follow-up. Secondary endpoints included the severity of these hernia-related complications, quality of life, and cumulative hernia recurrence rate. RESULTS: Thirty-four patients were included in the study. Sixteen patients were randomly assigned to elective repair and 18 to conservative treatment. After 24 months, 8 patients (50%) assigned to elective repair compared to 14 patients (77.8%) assigned to conservative treatment had a complication related to the umbilical hernia or its repair. A recurrent hernia was reported in 16.7% of patients who underwent repair. For the secondary endpoint, quality of life through the physical (PCS) and mental component score (MCS) showed no significant differences between groups at 12 months of follow-up (mean difference PCS 11.95, 95% CI - 0.87 to 24.77; MCS 10.04, 95% CI - 2.78 to 22.86). CONCLUSION: This trial could not show a relevant difference in overall morbidity after 24 months of follow-up in favor of elective umbilical hernia repair, because of the limited number of patients included. However, elective repair of umbilical hernia in patients with liver cirrhosis and ascites appears feasible, nudging its implementation into daily practice further, particularly for patients experiencing complaints. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01421550, on 23 August 2011.

Changes in mental health and drug use among men who have sex with men using daily and event-driven pre-exposure prophylaxis: Results from a prospective demonstration project in Amsterdam, the Netherlands.

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are at increased risk of mental health disorders and drug use. In GBMSM taking pre-exposure prophylaxis (PrEP) for HIV, the proportion engaging in risk behaviors could increase due to decreased perception in HIV risk. In turn, this could leave them further susceptible to mental health disorders. METHODS: The AMsterdam PrEP study (AMPrEP) is a demonstration project offering a choice of daily PrEP or event-driven PrEP regimen at the STI clinic of the Public Health Service of Amsterdam. Eligible participants were HIV-negative GBMSM and transgender people at risk of HIV, aged ≥18 years. We assessed anxiety and depressive mood disorders (Mental Health Inventory 5), sexual compulsivity (Sexual Compulsivity Scale), alcohol use disorder (Alcohol Use Disorder Identification Test), and drug use disorder (Drug Use Disorder Identification Test) using yearly self-administered assessments (August 2015-September 2018). The proportion of mental health problems were analyzed and changes over time and between regimen were assessed using a logistic regression model. Variables associated with the development or recovery of disorders were assessed using a multistate Markov model. OUTCOMES: Of 376 enrolled, we analyzed 341 participants with data at baseline and at least one follow-up visit. During a median follow-up of 2.5 years (IQR=2.3-2.7), the proportion assessed with sexual compulsivity decreased from 23% at baseline to 10% at the last visit (p<0.001) and drug use disorder decreased from 38% at baseline to 31% at the last visit (p = 0.004). No changes occurred in proportion assessed with anxiety/depressive mood disorders (20% at baseline, 18% at last visit, p = 0.358) or alcohol use disorder (28% at baseline, 22% at the last visit, p = 0.106). During follow-up, participants reported significant less use of alcohol (p<0.001), nitrites (p<0.001) and ecstasy (p<0.001). We found no differences between daily and event-driven PrEP users. The development and recovery of disorders during follow-up were highly interrelated. INTERPRETATION: Mental health disorders are prevalent among those initiating PrEP. We did not find increases in mental health disorders during PrEP use, but rather a decrease in sexual compulsivity and drug use disorders. The initial prevalence of mental health disorders in our study point at the continuous need to address mental health disorders within PrEP programs. FUNDING: ZonMw, H-TEAM, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.

Sex, drugs, and sexually transmitted infections: A latent class analysis among men who have sex with men in Amsterdam and surrounding urban regions, the Netherlands.

BACKGROUND: Men who have sex with men (MSM) are at high risk for sexually transmitted infections (STI) and often have sex while under the influence of drugs (sexualized drug use). We aimed to identify classes of MSM in Amsterdam and in surrounding urban regions with distinctive patterns of sexualized drug use and their association with STI. METHODS: In this cross-sectional study, data on MSM were collected at STI clinics in the Netherlands between September-December 2017. Information on drug use, sociodemographics and sexual risk behavior, including lab-confirmed STI (chlamydia, gonorrhea, syphilis and HIV) was collected and compared between Amsterdam and surrounding urban regions. Latent class analysis was used to identify classes with similar drug use patterns, which were then linked to sexual behavior and STI. RESULTS: We included 4461 MSM who were a median 35 years old (IQR = 27-47) and mostly Dutch (56.9 %). Use of all drugs was more often reported in Amsterdam compared to surrounding regions (p<0.001). We identified four different classes based on sexualized drug use among Amsterdam participants and three classes in surrounding regions. In both regions, polydrug use classes (compared to classes of no drug use; alcohol use; or few, various drugs) were defined by higher numbers of sexual partners (median range 8-15 vs 4-6, respectively) and higher STI prevalence (range 30.5%-31.8% vs 18.6%-22.8%, respectively). CONCLUSION: Given the high prevalence of risk behavior and STIs, MSM in urban settings partaking in sexualized polydrug use might benefit from tailored outreach, screening, and safe sex and drug use interventions.

Sarcomania? The Inapplicability of Sarcopenia Measurement in Predicting Incisional Hernia Development.

BACKGROUND: Incisional hernia is a frequent complication after abdominal surgery. A risk factor for incisional hernia, related to body composition, is obesity. Poor skeletal muscle mass might also be a risk factor, as it may result in weakness of the abdominal wall. However, it remains unknown if sarcopenia (i.e. low skeletal muscle mass) is a risk factor for incisional hernia. Therefore, this study aims to investigate whether a relation between sarcopenia and incisional hernia exists. METHODS: Patients from the STITCH trial, who underwent elective midline laparotomy, were included. Computed tomography examinations performed within 3 months preoperatively were used to measure the skeletal muscle index (SMI; cm2/m2). Primarily, SMI measured continuously, sarcopenia based on previously described cut-off values for the SMI, and sarcopenia as the lowest gender-specific SMI quartile were assessed as measures to predict incisional hernia occurrence. Secondary, the association between these three measures and post-operative complications was investigated. RESULTS: In total, 283 patients (45.2% male; mean age 63.7 years; mean BMI 25.36 kg/m2) were included, of whom 52 (18%) developed an incisional hernia. Mean SMI was 44.23 cm2/m2 (SD 7.77). The Nagelkerke value for the three measures of sarcopenia was about 0.020 (2.0%) for incisional hernia development. Logistic regressions with the three measures of sarcopenia did not show any predictive value of the model (area under the curve (AUC) of 0.67 for incisional hernia; 0.69 for post-operative complications). DISCUSSION: In this study, sarcopenia does not seem to be a risk factor for the development of an incisional hernia.

A post-market, prospective, multi-center, single-arm clinical investigation of Phasix™ mesh for VHWG grade 3 midline incisional hernia repair: a research protocol.

BACKGROUND: Incisional heia is a frequent complication of midline laparotomy. The use of mesh in hernia repair has been reported to lead to fewer recurrences compared to primary repair. However, in Ventral Hernia Working Group (VHWG) Grade 3 hernia patients, whose hernia is potentially contaminated, synthetic mesh is prone to infection. There is a strong preference for resorbable biological mesh in contaminated fields, since it is more able to resist infection, and because it is fully resorbed, the chance of a foreign body reaction is reduced. However, when not crosslinked, biological resorbable mesh products tend to degrade too quickly to facilitate native cellular ingrowth. Phasix™ Mesh is a biosynthetic mesh with both the biocompatibility and resorbability of a biological mesh and the mechanical strength of a synthetic mesh. This multi-center single-arm study aims to collect data on safety and performance of Phasix™ Mesh in Grade 3 hernia patients. METHODS: A total of 85 VHWG Grade 3 hernia patients will be treated with Phasix™ Mesh in 15 sites across Europe. The primary outcome is Surgical Site Occurrence (SSO) including hematoma, seroma, infection, dehiscence and fistula formation (requiring intervention) through 3 months. Secondary outcomes include recurrence, infection and quality of life related outcomes after 24 months. Follow-up visits will be at drain removal (if drains were not placed, then on discharge or staple removal instead) and in the 1st, 3rd, 6th, 12th, 18th and 24th month after surgery. CONCLUSION: Based on evidence from this clinical study Depending on the results this clinical study will yield, Phasix™ Mesh may become a preferred treatment option in VHWG Grade 3 patients. TRIAL REGISTRATION: The trial was registered on March 25, 2016 on clinicaltrials.gov: NCT02720042 .

Is rectal douching and sharing douching equipment associated with anorectal chlamydia and gonorrhoea? A cross-sectional study among men who have sex with men.

INTRODUCTION: Men who have sex with men (MSM) are at high risk for anorectal chlamydia and gonorrhoea infections. Many MSM use rectal douches in preparation for sex, which might break down the mucosal barrier function and facilitate the acquisition of STI. We determined whether rectal douching or sharing douching equipment was associated with anorectal chlamydia and gonorrhoea. METHODS: In a cross-sectional study among 994 MSM attending the STI outpatient clinic of Amsterdam between February and April 2011, data were collected on rectal douching, sexual behaviour and STI. We used multivariable logistic regression analysis to determine the association between rectal douching, including sharing of douching equipment, and anorectal chlamydia and gonorrhoea for those reporting receptive anal sex. We adjusted for other risk behaviour, that is, condom use, number of partners and HIV status. RESULTS: Of 994 MSM, 46% (n=460) practised rectal douching, of whom 25% (n=117) shared douching equipment. Median age was 39 years (IQR 30-47), median number of sex partners in the 6 months prior to consult was five (IQR 3-10) and 289 (29.0%) participants were HIV positive. The prevalence of anorectal chlamydia and/or gonorrhoea for those reporting receptive anal sex was 9.6% (n=96). In multivariable analysis, HIV positivity (aOR=2.2, 95% CI 1.3 to 3.6), younger age (aOR=2.5, CI 1.4 to 4.5 for those aged <35 years compared with those aged ≥45 years), and more sexual partners (aOR=1.2, 95% CI 1.0 to 1.5 for 1 log increase) were significantly associated with anorectal STI. However, rectal douching or sharing douching equipment were not significantly associated with anorectal chlamydia and/or gonorrhoea (p=0.647). CONCLUSIONS: Almost half of MSM used rectal douching and a quarter of these shared douching equipment. Though using douching equipment does not appear to contribute to anorectal chlamydia and gonorrhoea in this study, STI prevalence remains high and prevention strategies like early testing and treatment remain of utmost importance.

Seroprevalence of hepatitis E virus differs in Dutch and first generation migrant populations in Amsterdam, the Netherlands: a cross-sectional study.

BACKGROUND: In the last decade hepatitis E virus (HEV) is increasingly recognized as a cause of acute viral hepatitis in developed countries. HEV is transmitted via the fecal-oral route. In countries like the Netherlands, HEV infection is suspected to be a zoonosis but HEV may also be introduced by migrants. We studied the seroprevalence of HEV among different migrants, mainly Moroccans and Turks, and compared this to that of the native Dutch population in Amsterdam, the Netherlands. METHODS: Data were obtained from a cross-sectional survey of the adult Amsterdam population performed in 2004; the Amsterdam Health Monitor. A total of 1199 plasma samples were tested for IgG-and IgM antibodies to HEV using the Wantai kit according to instructions of the manufacturer. Basic demographic data (gender, age, country of birth, and age at immigration) were used in the analyses. Hepatitis A virus (HAV) serology data were available from a previous study. RESULTS: The total weighted anti-HEV IgG seroprevalence in the overall Amsterdam population was 26.7 %, based on 1199 samples. In the study population (not-weighted) this HEV seroprevalence was 157/426 (36.9 %) for the Dutch participants and it was 161/257 (62.6 %) for Moroccans, 99/296 (33.4 %) for Turks and 42/220 (19.1 %) for other ethnicities. HEV seroprevalence increased significantly with age. First-generation Moroccan migrants (44.0 %) had a significantly higher weighted HEV seroprevalence than the Dutch participants (29.7 %). In the first generation Turks (20.3 %) and first generation migrants from other countries (16.7 %) this weighted seroprevalence was lower, but this was only significant for the 'other ethnicities'. The median age of migration was significantly higher in the Moroccan and Turkish migrants who were HEV IgG positive versus HEV IgG negative. However, when stratifying for age at time of study, median migration age was only significantly different for HEV sero-status for younger Turks and younger 'other ethnicities'. HEV IgM antibodies were found in 0.6 % (n = 7) of participants and none were positive for HEV RNA, showing that there were no acute infections. Despite the common route of fecal-oral transmission for both viruses, there was no relation between HEV and HAV seropositivity. CONCLUSION: Within the multi-ethnical capital city of Amsterdam the HEV seroprevalence in first generation migrant populations differed from each other and from the autochthonous Dutch population. The relation between being HEV seropositive and a higher median age of migration suggests that younger migrants got more often infected in their country of origin than in the Netherlands.

Young male sex workers are at high risk for sexually transmitted infections, a cross-sectional study from Dutch STI clinics, the Netherlands, 2006-2012.

BACKGROUND: Male sex workers (MSW) are particularly exposed to sexually transmitted infections (STI) including HIV. In the Netherlands, data about STI among MSW are scarce. We estimated chlamydia, gonorrhoea, syphilis and HIV diagnoses among MSW attending STI clinics and determined associated factors to guide prevention policies. METHODS: Using 2006-2012 cross-sectional national surveillance data from Dutch STI clinics, we calculated the proportion of consultations with a positive test for any of three bacterial STI or HIV among MSW. Associated factors were determined by using Poisson logistic regression with robust variance. RESULTS: We identified 3,053 consultations involving MSW, of which 18.1 % included at least one positive bacterial STI test and 2.5 % a positive HIV test. Factors associated with bacterial STI and/or HIV diagnoses were respectively age groups < 35 y.o. and self-reporting homo- or bisexual preferences (aRR = 1.6; 95 % CI: 1.3-2.1), and age group 25-34 y.o. (aRR = 2.7; 95 % CI: 1.2-6.5) and self-reporting homo- or bisexual preferences (aRR = 24.4; 95 % CI: 3.4-176.9). Newly diagnosed and pre-existing HIV infection were associated with an increased risk for bacterial STI (aRR = 2.7, 95 % CI: 1.7-2.6 and aRR = 2.1, 95 % CI: 2.2-3.4 respectively). MSW with no history of HIV screening were more likely to be tested positive for HIV compared to those with a previous HIV-negative test (aRR = 2.6, 95 % CI: 1.6-4.3). CONCLUSION: Health promotion activities should target MSW who are young, homo- or bisexual, those who are HIV-infected or who have never been tested for HIV, to increase early diagnosis, prevention and treatment.

Trichomonas vaginalis and Mycoplasma genitalium: age-specific prevalence and disease burden in men attending a sexually transmitted infections clinic in Amsterdam, the Netherlands.

BACKGROUND: Men are not routinely tested for Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) in the Netherlands and, therefore, very few studies have looked into their prevalence and/or role in urogenital complaints in the Dutch male population. OBJECTIVE: To describe the age-specific prevalence and disease burden of TV and MG, and their co-occurrence with Chlamydia trachomatis (CT), in men attending the sexually transmitted infections (STI) clinic in Amsterdam, the Netherlands. METHODS: Urine samples and clinical data were collected from 526 men who have sex with women (MSW) and 678 men who have sex with men (MSM) attending the STI clinic. To investigate age as a risk factor, we oversampled older men. Urine samples were tested for TV and MG using molecular tests. RESULTS: The overall prevalence was 0.5% (6/1204) for TV and 3.1% (37/1204) for MG. Four out of the six TV cases were older than 40 years and all TV cases were MSW. No age trend was observed for MG, nor did MG prevalence differ between MSW and MSM. Co-infections between TV or MG and CT were rare. TV infection did not associate with urogenital symptoms, whereas 5.9% of men reporting urogenital symptoms were infected with MG. CONCLUSIONS: TV infection was rare in men, asymptomatic and was limited to the heterosexual network. MG infection was relatively common and equally prevalent among MSW and MSM of all ages. Most MG infections remained asymptomatic, however, our results suggest that up to 6% of urogenital complaints could be explained by MG infection.

From numeracy to arithmetic: Precursors of arithmetic performance in children with cerebral palsy from 6 till 8 years of age.

Children with cerebral palsy (CP) are generally delayed in arithmetic compared to their peers. The development of early numeracy performance in children with CP is not yet evident, nor have the factors associated with change over time been identified. Therefore, we examined the development of numeracy in children with CP over a two year period and studied which cognitive factors were predictive of arithmetic performance. A longitudinal study with three measurement waves separated by one year was conducted. 56 children participated (37 boys, M=6.0 years, SD=.58). Standardized tasks were used to assess verbal- and visual-spatial working memory, executive functioning, fine motor skills and early numeracy performance. In addition, experimental tasks were developed to measure counting and arithmetic. The results showed that early numeracy performance of children with CP increased between 6 and 8 years of age. Structural equation modelling showed that early numeracy was strongly related to arithmetic performance at the consecutive year. Working memory, counting and fine motor skills were all positively related to early numeracy performance a year later. Furthermore, working memory and fine motor skills were precursors of the development of early numeracy. Considering the importance of numeracy and arithmetic in daily life and in academic and work success, children with CP could substantially benefit from intervention programs aimed at increasing working memory and early numeracy performance.

Point-of-care management of urogenital Chlamydia trachomatis via Gram-stained smear analysis in male high-risk patients. Diagnostic accuracy and cost-effectiveness before and after changing the screening indication at the STI Clinic in Amsterdam.

OBJECTIVES: To measure the effect of changing the point-of-care (POC) testing algorithm of urogenital chlamydia for all male high-risk patients to those with only symptoms with respect to: diagnostic accuracy, loss to follow-up, correctly managed consultations and costs. METHODS: Retrospective comparison of the diagnostic accuracy and cost-effectiveness of Gram-stained urethral smear analysis for the POC management of urogenital Chlamydia trachomatis infections. Between 2008 and 2009 Gram-stained urethral smear analysis was offered to all men irrespective of symptoms; between 2010 and 2011 only to those with symptoms. The Aptima CT assay was the reference diagnostic test. RESULTS: The number of examined Gram-stained smears in the two periods was respectively 7185 (2008-2009 period) and 18,852 (2010-2011 period). The sensitivity of the Gram stain analysis was respectively 83.8% (95% CI 81.2% to 86.1%) and 91.0% (95% CI 89.5% to 92.3%) (p<0.001). The specificity was respectively 74.1% (95% CI 73.0% to 75.2%) and 53.1% (95% CI 51.8% to 54.4%) (p<0.001). The positive predictive value was low in both periods, respectively 31.7% (95% CI 29.8% to 33.6%) and 35.6% (95% CI 34.1% to 37.1%) (p=0.002), whereas the negative predictive value was high, respectively 97.0% (95% CI 96.4% to 97.4%) and 95.4% (95% CI 94.6% to 96.1%) (p=0.002). The loss to follow-up rate between 2008-2009 and 2010-2011 was, respectively, 1.8% (95% CI 1.0% to 2.9%) vs 2.3% (95% CI 1.7% to 3.0%) (p=0.36). There was a small difference in overtreatment, 68.0% (95% CI 66.0% to 69.8%) vs 64.1% (95% CI 62.6% to 65.5%) (p=0.001). The cost per correctly managed consultation was 14.3% lower in the 2010-2011 period (€94.31 vs €80.82). The percentage of delayed treated infections was significantly lower in the 2008-2009 period (10.5%) compared with the 2010-2011 period (22.8%) (p<0.001). CONCLUSIONS: With a high sensitivity in male high-risk patients, the Gram-stained urethral smear is a useful POC test to detect urogenital C. trachomatis. When offered only to men with urogenital symptoms the specificity decreases but the cost per correctly managed consultation is reduced with 14.3% without a significant difference in loss to follow-up but with a significantly higher rate of delayed treatment.

Comparison of two Gram stain point-of-care systems for urogenital gonorrhoea among high-risk patients: diagnostic accuracy and cost-effectiveness before and after changing the screening algorithm at an STI clinic in Amsterdam.

OBJECTIVES: To compare point-of-care (POC) systems in two different periods: (1) before 2010 when all high-risk patients were offered POC management for urogenital gonorrhoea by Gram stain examination; and (2) after 2010 when only those with symptoms were offered Gram stain examination. METHODS: Retrospective comparison of a Gram stain POC system to all high-risk patients (2008-2009) with only those with urogenital symptoms (2010-2011) on diagnostic accuracy, loss to follow-up, presumptively and correctly treated infections and diagnostic costs. Culture was the reference diagnostic method. RESULTS: In men the sensitivity of the Gram stain was 95.9% (95% CI 93.1% to 97.8%) in 2008-2009 and 95.4% (95% CI 93.7% to 96.8%) in 2010-2011, and in women the sensitivity was 32.0% (95% CI 19.5% to 46.7%) and 23.1% (95% CI 16.1% to 31.3%), respectively. In both periods the overall specificity was high (99.9% (95% CI 99.8% to 100%) and 99.8% (95% CI 99.7% to 99.9%), respectively). The positive predictive value (PPV) and negative predictive value (NPV) before and after 2010 were also high: PPV 97.0% (95% CI 94.5% to 98.5%) and 97.7% (95% CI 96.3% to 98.6%), respectively; NPV 99.6% (95% CI 99.4% to 99.7%) and 98.8% (95% CI 98.5% to 99.0%), respectively. There were no differences between the two time periods in loss to follow-up (7.1% vs 7.0%). Offering Gram stains only to symptomatic high-risk patients as opposed to all high-risk patients saved €2.34 per correctly managed consultation (a reduction of 7.7%). CONCLUSIONS: The sensitivity of the Gram stain is high in men but low in women. When offered only to high-risk patients with urogenital symptoms, the cost per correctly managed consultation is reduced by 7.7% without a significant difference in accuracy and loss to follow-up.

Cognitive precursors of arithmetic development in primary school children with cerebral palsy.

The aim of this study was to examine the development of arithmetic performance and its cognitive precursors in children with CP from 7 till 9 years of age. Previous research has shown that children with CP are generally delayed in arithmetic performance compared to their typically developing peers. In children with CP, the developmental trajectory of the ability to solve addition- and subtraction tasks has, however, rarely been studied, as well as the cognitive factors affecting this trajectory. Sixty children (M=7.2 years, SD=.23 months at study entry) with CP participated in this study. Standardized tests were administered to assess arithmetic performance, word decoding skills, non-verbal intelligence, and working memory. The results showed that the ability to solve addition- and subtraction tasks increased over a two year period. Word decoding skills were positively related to the initial status of arithmetic performance. In addition, non-verbal intelligence and working memory were associated with the initial status and growth rate of arithmetic performance from 7 till 9 years of age. The current study highlights the importance of non-verbal intelligence and working memory to the development of arithmetic performance of children with CP.

Ultrasonographically measured testicular volumes in 0- to 6-year-old boys.

BACKGROUND: Aside from converted data from orchidometer measurements, there are no referential values for testicular volume ultrasound measurements in children available. Therefore, the aim of this study was to obtain ultrasonographically measured normative data for testicular volumes in 0- to 6-year-old boys. METHODS: A total of 344 boys from different ethnic backgrounds were studied. For the ultrasound measurements, an Aloka SSD-900 was used with a 7.5 mHz linear transducer. Testicular volume was calculated using the formula: length x width x height x (pi/6). RESULTS: No differences were found either between the various ethnic groups or between the left and right testicle. Mean testicular volume was compared between the different age categories. Mean testicular volume increases significantly in the first 5 months from 0.27 to 0.44 cm(3) after which the volume decreases to 0.31 cm(3) at approximately 9 months. During the following years, testicular volume remains stable. CONCLUSIONS: This study provides normal values for ultrasonographically measured testicular volumes in 0- to 6-year-old boys. Ultrasound is a valid method to measure small pre-pubertal testicles as it is able to detect minor changes in volume in relation to established physiological changes in the first year of life.