Simultaneous granular cell tumor and seminoma in the descended testis of a cryptorchid rabbit.

Testicular tumors are rarely reported in rabbits. In this case study, a 4-year-old Holland lop rabbit, previously diagnosed with unilateral cryptorchidism, was presented because of enlargement of the descended testis. The rabbit was clinically normal. Following unilateral orchiectomy and scrotal ablation, histopathological analysis revealed 2 distinct types of testicular tumor in the descended testis: a granular cell tumor and a seminoma. To the best of the author's knowledge, this is the first documented report of simultaneous testicular tumors in the testis of a rabbit with unilateral cryptorchidism.

Tumeur à cellules granulaires et séminome simultanés dans le testicule descendu d'un lapin cryptorchideLes tumeurs testiculaires sont rarement rapportées chez le lapin. Dans cette étude de cas, un lapin Holland Lop de 4 ans, précédemment diagnostiqué avec une cryptorchidie unilatérale, a été présenté en raison d'une hypertrophie du testicule descendu. Le lapin était cliniquement normal. Après orchidectomie unilatérale et ablation scrotale, l'analyse histopathologique a révélé 2 types distincts de tumeur testiculaire dans le testicule descendu : une tumeur à cellules granuleuses et un séminome. À la connaissance de l'auteur, il s'agit du premier rapport documenté de tumeurs testiculaires simultanées dans le testicule d'un lapin atteint de cryptorchidie unilatérale.(Traduit par Dr Serge Messier).

Characteristics, treatment and care of pregnant women living with hepatitis B in England: findings from a national audit.

Around 0.4% of pregnant women in England have chronic hepatitis B virus (HBV) infection and need services to prevent vertical transmission. In this national audit, sociodemographic, clinical and laboratory information was requested from all maternity units in England for hepatitis B surface antigen-positive women initiating antenatal care in 2014. We describe these women's characteristics and indicators of access to/uptake of healthcare. Of 2542 pregnancies in 2538 women, median maternal age was 31 [IQR 27, 35] years, 94% (1986/2109) were non-UK born (25% (228/923) having arrived into the UK <2 years previously) and 32% (794/2473) had ⩾2 previous live births. In 39%, English levels were basic/less than basic. Antenatal care was initiated at median 11.3 [IQR 9.6, 14] gestation weeks, and 'late' (⩾20 weeks) in 10% (251/2491). In 70% (1783/2533) of pregnancies, HBV had been previously diagnosed and 11.8% (288/2450) had ⩾1 marker of higher infectivity. Missed specialist appointments were reported in 18% (426/2339). Late antenatal care and/or missed specialist appointments were more common in pregnancies among women lacking basic English, arriving in the UK ⩽2 years previously, newly HBV diagnosed, aged <25 years and/or with ⩾2 previous live births. We show overlapping groups of pregnant women with chronic HBV vulnerable to delayed or incomplete care.

Vertical transmission of Zika virus and its outcomes: a Bayesian synthesis of prospective studies.

BACKGROUND: Prospective studies of Zika virus in pregnancy have reported rates of congenital Zika syndrome and other adverse outcomes by trimester. However, Zika virus can infect and damage the fetus early in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. We aimed to provide the first estimates of underlying vertical transmission rates and adverse outcomes due to congenital infection with Zika virus by trimester of exposure. METHODS: This was a Bayesian latent class analysis of data from seven prospective studies of Zika virus in pregnancy. We estimated vertical transmission rates, rates of Zika-virus-related and non-Zika-virus-related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters and used information from women in comparison groups with no PCR-confirmed infection, where available. FINDINGS: The estimated mean risk of vertical transmission was 47% (95% credible interval 26 to 76) following maternal infection in the first trimester, 28% (15 to 46) in the second, and 25% (13 to 47) in the third. 9% (4 to 17) of deliveries following infections in the first trimester had symptoms consistent with congenital Zika syndrome, 3% (1 to 7) in the second, and 1% (0 to 3) in the third. We estimated that in infections during the first, second, and third trimester, respectively, 13% (2 to 27), 3% (-5 to 14), and 0% (-7 to 11) of pregnancies had adverse outcomes attributable to Zika virus infection. Diagnostic sensitivity of markers of congenital infection was lowest in the first trimester (42% [18 to 72]), but increased to 85% (51 to 99) in trimester two, and 80% (42 to 99) in trimester three. There was substantial between-study variation in the risks of vertical transmission and congenital Zika syndrome. INTERPRETATION: This preliminary analysis recovers the causal effects of Zika virus from disparate study designs. Higher transmission in the first trimester is unusual with congenital infections but accords with laboratory evidence of decreasing susceptibility of placental cells to infection during pregnancy. FUNDING: European Union Horizon 2020 programme.

Researching Zika in pregnancy: lessons for global preparedness.

Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015-16 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies.

Modelling the effect of the introduction of antenatal screening for group B Streptococcus (GBS) carriage in the UK.

OBJECTIVES: To estimate the potential impact of the addition of culture-based screening for group B streptococcus (GBS) carriage in pregnancy to a risk-based prevention policy in the UK. We aimed to establish agreement within a multidisciplinary group of key stakeholders on the model input parameters. DESIGN: Deterministic model using a consensus approach for the selection of input parameters. SETTING AND PARTICIPANTS: A theoretical annual cohort of 711 999 live births in the UK (excluding births by elective caesarean section). INTERVENTIONS: Culture-based screening for GBS at 35-37 weeks of pregnancy added to the recommended risk-based prevention policy in place on the date of modelling. OUTCOME MEASURES: Outcomes assessed included use of intrapartum antibiotic prophylaxis (IAP), early onset GBS (EOGBS), EOGBS mortality, severe EOGBS-related morbidity and maternal penicillin anaphylaxis. RESULTS: With no prophylaxis strategy, the model estimated that there would be 421 cases of culture positive EOGBS in a year (0.59/1000 live births). In the risk-based prophylaxis scenario, 30 666 women were estimated to receive IAP and 70 cases of EOGBS were prevented. Addition of screening resulted in a further 96 260 women receiving IAP and the prevention of an additional 52 to 57 cases of EOGBS. This resulted in the prevention of three EOGBS deaths and four cases of severe disability. With screening, an additional 1675 to 1854 women receive IAP to prevent one EOGBS case and 24 065 to 32 087 receive IAP to prevent one EOGBS death. CONCLUSIONS: The evidence base available for a broad range of model input parameters was limited, leading to uncertainty in the estimates produced by the model. Where data was limited, the model input parameters were agreed with the multidisciplinary stakeholder group, the first time this has been done to our knowledge. The main impact of screening is likely to be on the large group of low-risk women where the clinical impact of EOGBS tends to be less severe. This model suggests that the reduction in mortality and severe disability due to EOGBS with antenatal GBS screening is likely to be very limited, with a high rate of overdetection and overuse of antibiotics.

Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011.

OBJECTIVES: To analyze mother-to-child HIV transmission (MTCT) rates over time in light of changes in management, demographic, and pregnancy characteristics. DESIGN: Population-based surveillance data on diagnosed HIV-positive women and their infants are routinely collected in the UK and Ireland. METHODS: A total of 12486 singleton pregnancies delivered in 2000-2011 were analyzed. HIV infection status was available for 11515 infants (92.2%). RESULTS: The rate of MTCT declined from 2.1% (17/816) in 2000-2001 to 0.46% (nine of 1975, 95% confidence interval: 0.21-0.86%) in 2010-2011 (trend, P=0.01), because of a combination of factors including earlier initiation of antenatal combination antiretroviral therapy (cART). Excluding 63 infants who were breastfed or acquired HIV postnatally, MTCT risk was significantly higher for all modes of delivery in women with viral load of 50-399  copies/ml (1.0%, 14/1349), compared with viral load of less than 50 copies/ml (0.09%, six of 6347, P<0.001). Among the former (viral load 50-399 copies/ml), the risk of MTCT was 0.26% (two of 777) following elective cesarean section and 1.1% (two of 188) following planned vaginal delivery (P=0.17), excluding in-utero transmissions. MTCT probability declined rapidly with each additional week of treatment initially, followed by a slower decline up to about 15 weeks of cART, with substantial differences by baseline viral load. CONCLUSION: MTCT rates in the UK and Ireland have continued to decline since 2006, reaching an all-time low of 5 per 1000 in 2010-2011. This was primarily because of a reduction in transmissions associated with late initiation or nonreceipt of antenatal cART, and an increase in the proportion of women on cART at conception.

Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom.

BACKGROUND: Congenital cytomegalovirus (CMV) is an important cause of neurological problems, particularly sensorineural hearing loss, but data on long-term sequelae and the impact of nonprimary maternal infection are limited. We report updated findings on childhood outcomes from 2 large prospective studies. METHODS: Pregnant women in Malmö, Sweden, and London, United Kingdom, were included between 1977 and 1986, and newborns were screened for CMV (virus culture of urine or saliva). Cases and matched controls underwent regular, detailed developmental assessments up to at least age 5 years. RESULTS: One hundred seventy-six congenitally infected infants were identified among >50 000 screened (Malmö: 76 [4.6/1000 births]; London: 100 [3.2/1000 births]); 214 controls were selected. Symptoms were recorded in 11% of CMV-infected neonates (19/176) and were mostly mild; only 1 neonate had neurological symptoms. At follow-up, 7% of infants (11/154) were classified as having mild, 5% (7/154) moderate, and 6% (9/154) severe neurological sequelae. Four of 161 controls (2%) had mild impairment. Among children symptomatic at birth, 42% (8/19) had sequelae, versus 14% (19/135) of the asymptomatic infants (P = .006). All moderate/severe outcomes were identified by age 1; mild sequelae were first identified at age 2-5 years in 6 children, and age 6-7 years in 3. Among the 16 children with moderate/severe outcomes, 2 had mothers with confirmed and 7 with presumed nonprimary infection. CONCLUSIONS: Moderate or severe outcomes were reported in 11% of children with congenital CMV identified through population screening, all by 1 year; all impairment detected after this age was mild. Nonprimary infections contributed substantially to the burden of childhood congenital CMV disease.

Outcomes of childhood epilepsy at age 33 years: a population-based birth-cohort study.

PURPOSE: There is uncertainty about health and socioeconomic outcomes of children with epilepsy, knowledge of adult outcomes, and factors associated with adverse outcomes are essential to guide prognosis, improve management, and determine appropriate allocation of resources. METHODS: A subgroup of 101 children with epilepsy (onset ≤ age 16 years) were previously identified and reported from the 1958 National Child Development Study (NCDS), a national United Kingdom birth cohort study. In the current study we examine outcomes of this unique childhood epilepsy subgroup at age 33 compared to unaffected NCDS cohort members in mental and general health, education and employment, marriage, and parenthood. Multivariable regression analyses were used to investigate factors (including etiology, cognitive development, parental interest, and childhood anxiety/depression at age 11 years) associated with adverse outcomes. key findings: Sixty-five (66%) were still participating at 33 years. Median follow-up after epilepsy onset was 28 years (range 17-33 years). Thirty participants [46%, 95% confidence interval (CI) 35-58] had epilepsy onset <5 years, 32 (49%, 95% CI 37-61) had "symptomatic" epilepsy, and 33 (51%, 95% CI 39-63) had idiopathic epilepsy. Thirty-one participants (48%) reported being seen by their doctor for epilepsy in the preceding year, 27 (42%) were registered disabled, 39 (60%) had a drivers license, and 42 (65%) thought their epilepsy made it harder to get/keep a paid job. People who had childhood epilepsy had an increased risk of death [standardized mortality rate (SMR) 3.1, 95% CI 1.1-6.1]. Childhood epilepsy was associated with poor general and mental health at 33 years on univariable analyses, but not after adjusting for childhood cognitive development/comorbidities and anxiety over acceptance by peers/adults at age 11. Childhood epilepsy was an independent risk factor for not being married [odds ratio (OR) 0.45, 95% CI 0.05-0.94] or being a parent (OR 0.67, 95% CI 0.42-0.91). People with childhood epilepsy and poor cognitive development compared to those with poor cognitive development without epilepsy had a greater proportion with subsequent poor mental health (56% vs. 24%, difference in proportion 33%, 95% CI 12-50), and a lesser proportion who married (39% vs. 78%, difference in proportion -39%, 95% CI -56 to -19). SIGNIFICANCE: Compared to the unaffected population, children with epilepsy with good cognitive development/without comorbidities have similar adult health, educational, and employment outcomes but have difficulties with establishing and maintaining personal relationships. A combination of having childhood epilepsy plus poor cognitive development is more likely to be associated with adverse outcomes compared to having poor cognitive development without childhood epilepsy. Children with epilepsy have increased risk of death compared to the rest of the population. Pharmacologic management alone is inadequate and long-term psychosocial support is needed.

Surveillance of congenital cytomegalovirus in the UK and Ireland.

OBJECTIVE: To explore the presentation and management of congenital cytomegalovirus (CMV) identified through routine clinical investigations, and ascertain outcome in early childhood. DESIGN: Active population-based surveillance. SETTING: UK and Ireland. METHODS: Infants born in 2001-2002 with confirmed or suspected congenital CMV infection were reported through the British Paediatric Surveillance Unit, and clinicians completed questionnaires on presentation, diagnosis, management and subsequent outcome. RESULTS: 86 confirmed and 70 possible cases of congenital CMV infection were reported. Over a third (27/72) of singleton infants with confirmed and 44% (27/61) with possible congenital infection were preterm (<37 weeks gestation). Among confirmed cases, 75% (64/85) presented with neonatal manifestations compatible with congenital CMV, over half (34/64) of whom had neurological signs; 17 infants were treated with gancyclovir. Among confirmed cases with information on outcome, 31% (24/78) were developing normally, 18% (14/78) had mild, 24% (19/78) moderate and 14% (11/78) severe sequelae, and 13% (10/78) had died. Median age at follow-up among survivors was 18 months (IQR 15-22 months). Children with neonatal CMV manifestations were significantly more likely than those without to have moderate or severe outcomes (including death) (60%, 36/60, vs 22%, 4/18, p=0.001). 27% of survivors (17/63) had bilateral hearing loss. CONCLUSIONS: The number of confirmed cases of diagnosed congenital CMV reported in this study was lower than expected, highlighting the need for early and appropriate investigations when congenital infection is suspected. Due to the unexpectedly high proportion of preterm infants, resulting from differential case ascertainment, it was difficult to distinguish prematurity and CMV-related symptoms.

Myopia over the lifecourse: prevalence and early life influences in the 1958 British birth cohort.

PURPOSE: To investigate the hypothesis that the excessive growth of the eye in myopia is associated with general growth and thus influenced by early life biological and social factors, and that these associations underlie recent secular trends of increasing prevalence and severity of myopia. DESIGN: Cohort study. PARTICIPANTS: A total of 2487 randomly selected 44-year-old members of the 1958 British birth cohort (27% subsample). METHODS: Diverse and detailed biological, social, and lifestyle data have been collected by following members since birth through a series of clinical examinations or face-to-face interviews carried out by trained examiners. At 44 years, cohort members underwent autorefraction using the Nikon Retinomax 2 (Nikon Corp., Tokyo, Japan) under non-cycloplegic conditions. A lifecourse epidemiologic approach, based on 4 sequential multivariable "life stage" models (preconceptional; prenatal, perinatal, and postnatal; childhood; and adult), was used to examine the influence of early life biological, social and lifestyle factors, growth patterns, and "eye-specific" factors on myopia. MAIN OUTCOME MEASURES: Myopia severity (all, mild/moderate: spherical equivalent -0.75 to -5.99 diopters [D]; severe: ≥-6.00 D extreme vs. emmetropia -0.74 to +0.99 D) and myopia onset (early [<16 years] vs. later). RESULTS: A total of 1214 individuals (49%; 95% confidence interval, 48.8-50.8) were myopic (late onset in 979 [80.6%]). Myopia was positively associated with low birthweight for gestational age, gender, greater maternal age, higher paternal occupational social class, and maternal smoking in early pregnancy. Myopia was independently associated with proxy markers of near work and educational performance, with some differences by onset and severity. In adults, greater height and higher educational attainment and socioeconomic status were associated with myopia. CONCLUSIONS: Trends in the key influences on child health and growth identified as novel putative risk factors in this study are consistent with global trends of increasing myopia: increasing births to older mothers, increasing rates of intrauterine growth retardation and survival of affected children, increasing persistence of smoking in pregnancy, and changing socioeconomic status. Prospects for prevention of myopia would be improved by a paradigm shift in myopia research, with lifecourse and genetic epidemiologic approaches applied in tandem in large unselected populations.

Improving detection of blindness in childhood: the British Childhood Vision Impairment study.

OBJECTIVES: In industrialized countries, there are established programs of childhood vision screening and surveillance, but little is known about their performance. We investigated the patterns of presentation/detection and early treatment of a nationally representative cohort of children with severe visual impairment or blindness (SVI/BL) in 1 year (2000) in the United Kingdom. METHODS: All children who were younger than 16 years and had a new diagnosis of SVI/BL were identified by active surveillance through the British Ophthalmological and Pediatric Surveillance Units. Data that were collected up to 1 year after diagnosis included sociodemographic characteristics, detection of SVI/BL, nonophthalmic disorders/impairments, ophthalmic findings, and early management. RESULTS: Of 439 identified children, 65% were younger than 1 year at diagnosis, 28% were of nonwhite ethnicity, and 40% in the worst quintile of deprivation score. A total of 77% had associated nonophthalmic disorders/impairments. Although 70% had established symptoms or signs at diagnosis by a health professional, parents had suspected blindness in only 47%. A quarter of isolated SVI/BL was detected through routine vision screening; however, 46% of children's SVI/BL and associated nonophthalmic disorders/impairments were diagnosed through a clinical surveillance examination undertaken because of high risk for a specific eye disease. CONCLUSIONS: The "patient journey" of children with visual impairment is markedly influenced by the presence of additional impairments/chronic diseases. Parents' understanding of normal visual development needs to be improved. Increasingly, new evidence-based formal programs of clinical (ophthalmic) surveillance are needed in response to the changing population of children who are at risk for blinding eye disease.

In utero exposure to antiretroviral therapy: feasibility of long-term follow-up.

Most uninfected children born to diagnosed HIV-infected women in the United Kingdom (UK) are exposed to antiretroviral therapy (ART) in utero and neonatally, and concerns exist about potential adverse effects of such exposure. We explored the feasibility of using national clinic-based follow-up to investigate the association between ART exposure and adverse health events occurring after the neonatal period. Active surveillance of obstetric and paediatric HIV infection is conducted through the National Study of HIV in Pregnancy and Childhood (NSHPC). Between 2002 and 2005, health professionals enrolled previously notified uninfected children in a consented follow-up study (the CHildren exposed to AntiRetroviral Therapy (CHART) study). Follow-up information was collected opportunistically using a standard questionnaire. Of 2104 eligible uninfected children born in the UK between 1996 and 2004, 704 (33.5%) were enrolled in CHART; parents of 4.8% (100/2104) declined, 2.8% (59/2104) had gone abroad, 21.6% (455/2104) were not contactable, and the remaining 37.3% (786/2104) were not enrolled mainly because of lack of clinic resources or unwillingness of health professionals to approach the families. Demographic characteristics and type of ART exposure for enrolled and non-enrolled children were similar. Latest information on enrolled children was available at a median age of 24 months. Minor childhood ailments were reported in the majority of children, febrile seizures in 1.6% (11/704), and major health problems in 3.8% (27/704). It was reassuring that prevalence of these outcomes was within UK norms, but numbers were small and duration of follow-up was limited. The difficulties encountered in enrolling and retaining children in this study indicate that comprehensive clinic-based follow-up of ART-exposed uninfected children is not practical. Alternative approaches are required; a robust, secure data linkage protocol would provide a more feasible and sustainable system for long-term monitoring of in utero ART exposure.

Use of stored dried blood spots for retrospective diagnosis of congenital CMV.

The diagnosis of congenital cytomegalovirus infection cannot be made with certainty in children presenting after the perinatal period, unless stored early samples are available for diagnostic testing. This has led to uncertainty in confirming the overall contribution of CMV to hearing loss and neurodevelopmental impairment. The use of dried blood spots (DBSs) to retrospectively diagnose infection in children with compatible symptoms may be helpful diagnostically although there are ongoing uncertainties regarding the stability of viral DNA in cards, the risk of contamination between cards, and sensitivity and specificity in a clinical setting. This report aims to address these areas and evaluate the use of DBS testing in our hands in the United Kingdom to date. Results from testing artificially prepared cards and cards from three populations of children suggest a high specificity for congenital CMV infection and a good sensitivity for cases where sensorineural hearing loss is caused by congenital CMV.

Visual function in working-age adults: early life influences and associations with health and social outcomes.

PURPOSE: To investigate how visual function in mid-adult life is associated with health and social outcomes and, using life-course epidemiology, whether it is influenced by early life biological and social factors. DESIGN: Population-based cohort study. PARTICIPANTS: Nine thousand three hundred thirty members of the 1958 British birth cohort at age 44 or 45 years. METHODS: Distance, near, and stereo vision were assessed as part of a broader biomedical examination. Logistic, multinomial, and proportional odds ordinal logistic regression were used, as appropriate, to assess the association between these vision functions and both key early life influences and health and social outcomes in mid-adult life. MAIN OUTCOME MEASURES: Distance, near, and stereo acuities and health and social outcomes. RESULTS: In mid-adult life, vision function (across the full spectrum of both type and level of function) is associated with unemployment resulting from permanent sickness, lower socioeconomic status, and poorer general health (for example, for blindness; odds ratios were 2.5, 2.6, and 1.2, respectively). Also, impaired visual functions in mid-adult life are associated with a low birthweight, being small for gestational age, maternal smoking in pregnancy, and markers of socioeconomic deprivation in childhood (for example, for impaired distance acuity; odds ratios were 1.4, 1.3, 1.02, and 1.1, respectively). CONCLUSIONS: Although relatively uncommon in working-age adults, impaired vision can have important adverse consequences, which highlights the value of investigating visual function in the broader context of health and social functioning. In addition, visual function in adult life may be influenced directly by key prenatal and childhood biological and social determinants of general health. Thus, application of life-course epidemiology to complex chronic ophthalmic diseases of adult life such as glaucoma or macular degeneration is likely to prove valuable in elucidating whether and how biological, social, and lifestyle factors contribute to the cause.

Antiretroviral therapy and congenital abnormalities in infants born to HIV-infected women in the UK and Ireland, 1990-2007.

OBJECTIVE: To explore the rate of reported congenital abnormalities in infants exposed to antiretroviral therapy in utero. DESIGN: Comprehensive national surveillance study in the UK and Ireland. METHODS: Births to diagnosed HIV-infected women are reported to the National Study of HIV in Pregnancy and Childhood. Infants born between 1990 and 2007 were included. RESULTS: The rate of reported major and minor congenital abnormality was 2.8% (232/8242) overall, and there was no significant difference by timing of ART exposure: 2.8% (14/498) in unexposed infants, 2.7% (147/5427) following second or third trimester exposure, and 3.1% (53/1708) following first trimester exposure (P = 0.690). There was no difference in abnormality rates by class of ART exposure in the first trimester (P = 0.363), and no category of abnormality was significantly associated with timing of ART, although numbers in these groups were small. There was no increased risk of abnormalities in infants exposed to efavirenz (P = 0.672) or didanosine (P = 0.816) in the first trimester. CONCLUSION: These findings, based on a large, national, unselected population provide further reassurance that ART in utero does not pose a major risk of fetal anomaly.