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.

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.

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.

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.

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.

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 impairment and vision-related quality of life in working-age adults: findings in the 1958 British birth cohort.

PURPOSE: To describe the prevalence of impaired vision and its relative burden, together with the prevalence of impaired vision-related quality of life (VRQOL), and investigate associations with social outcomes in a contemporary and nationally representative population of working age adults. DESIGN: Population-based cross-sectional study. PARTICIPANTS: We included 9330 members of the 1958 British birth cohort at age 44 and 45 years. METHODS: "Habitual" and "best achieved" distance visual acuity in each eye, binocular near vision acuity and stereoacuity (three dimensional/depth perception) were tested during a broader biomedical examination. VRQOL was assessed using the Vision-related Quality of Life Core Measure 1 (VCM1), a validated, 10-item, self-complete instrument. Logistic and proportional odds ordinal logistic regression were used to calculate odds ratios (ORs) of the association of VRQOL with visual acuities and social outcomes. MAIN OUTCOME MEASURES: Distance, near, and stereo acuities and VRQOL and social outcomes. RESULTS: Of the 1.3% (124) of those with visual loss that precluded driving, a further 0.75% (70) were visually impaired or severely visually impaired and 0.15% (14) blind, the latter accounting for 19% total population (all ages) burden of blindness. Impairment of VRQOL is strongly associated with impaired distance, near, and stereo vision, as well as with adverse occupational and other social outcomes. However, VRQOL impairment is also sometimes reported with unilateral or mild bilateral visual loss. CONCLUSIONS: Although impaired vision in working age adults is relatively uncommon, it confers important adverse consequences for the "health and wealth" of the public. This may be captured best by assessment of VRQOL in addition to objective visual function. Ophthalmic disorders occurring or impacting in middle life should be given a higher priority than currently in national and international strategies against avoidable visual disability. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

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.

Socioeconomic deprivation independent of ethnicity increases status epilepticus risk.

BACKGROUND: A higher incidence of convulsive status epilepticus (CSE) has been reported in nonwhite compared to white populations. Socioeconomic factors can be intricately involved in observed ethnic "effects," and the importance of socioeconomic status on health conditions is widely recognized. Understanding the effect of socioeconomic factors on CSE would provide insights into etiology and management, leading to the development of novel prevention strategies. METHODS: From a population-based UK study on childhood CSE, we tested the hypothesis that socioeconomic deprivation independent of ethnicity increases the risk of childhood CSE. Home postal codes were used to measure the socioeconomic status of the neighborhood in which patients lived relative to that of the borough in which the neighborhood was located. The child's ethnicity was reported by parent(s). Relationships between socioeconomic status, ethnicity, and incidence were investigated using Poisson regression analysis. RESULTS: A total of 176 children were enrolled. The incidence of CSE in nonwhite children [18.5, 95% confidence interval (CI) 13.7-23.3/100,000/year] was 1.8 (95% CI 1.3-2.4) times greater than for white children (10.5, 95% CI 7.9-13.1/100,000/year) (p < 0.0005). Socioeconomic deprivation and Asian ethnicity were independently associated with increased incidence. For each point increase in Index of Multiple Deprivation (IMD) 2004, there was a 1.03 cumulative increased relative risk (95% CI 1.01-1.06, p = 0.007). Asian children were 5.7 times (95% CI 1.7-18.9) more likely than white children to have a first-ever episode of CSE (p = 0.004). Socioeconomic and ethnicity effects were related to etiology of CSE. INTERPRETATION: Ethnic and socioeconomic factors independently affect risk for prolonged febrile seizures and acute symptomatic CSE, but not for other types of childhood CSE.

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.

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.

Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study.

BACKGROUND: Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE. METHODS: We collected data prospectively on children in north London, UK, who had episodes of CSE (ascertainment 62-84%). The factors associated with seizure termination after first-line and second-line therapies, episodes of CSE lasting for longer than 60 min, and respiratory depression were analysed with logistic regression. Analysis was per protocol, and adjustment was made for repeat episodes in individuals. RESULTS: 182 children of median age 3.24 years (range 0.16-15.98 years) were included in the North London Convulsive Status Epilepticus in Childhood Surveillance Study (NLSTEPSS) between May, 2002, and April, 2004. 61% (147) of 240 episodes were treated prehospital, of which 32 (22%) episodes were terminated. Analysis with multivariable models showed that treatment with intravenous lorazepam (n=107) in the accident and emergency department was associated with a 3.7 times (95% CI 1.7-7.9) greater likelihood of seizure termination than was treatment with rectal diazepam (n=80). Treatment with intravenous phenytoin (n=32) as a second-line therapy was associated with a 9 times (95% CI 3-27) greater likelihood of seizure termination than was treatment with rectal paraldehyde (n=42). No treatment prehospital (odds ratio [OR] 2.4, 95% CI 1.2-4.5) and more than two doses of benzodiazepines (OR 3.6, 1.9-6.7) were associated with episodes that lasted for more than 60 min. Treatment with more than two doses of benzodiazepines was associated with respiratory depression (OR 2.9, 1.4-6.1). Children with intermittent CSE arrived at the accident and emergency department later after seizure onset than children with continuous CSE did (median 45 min [range 11-514 min] vs 30 min [5-90 min]; p<0.0001, Mann-Whitney U test); for each minute delay from onset of CSE to arrival at the accident and emergency department there was a 5% cumulative increase in the risk of the episode lasting more than 60 min. INTERPRETATION: These data add to the debate on optimum emergency treatment of childhood CSE and suggest that the current guidelines could be updated.

Monitoring death and cancer in children born to HIV-infected women in England and Wales: use of HIV surveillance and national routine data.

There may be long-term adverse health effects of in-utero antiretroviral therapy exposure. Data on children reported through national HIV surveillance were linked to routinely collected cancer and death data: a process known as "flagging". Ninety-five per cent (2612) of reported children born in 2001-2004 in England or Wales who were uninfected or of indeterminate infection status were flagged. By the end of 2005, no cancers and 14 deaths (three uninfected and 11 indeterminate) had been notified.

Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland.

OBJECTIVE: To explore the association between antiretroviral therapy in pregnancy and premature delivery, birthweight, stillbirth and neonatal mortality, in pregnancies in HIV-infected women delivering between 1990 and 2005. DESIGN: Pregnancies in women with diagnosed HIV infection in the UK and Ireland are notified to the National Study of HIV in Pregnancy and Childhood (NSHPC) through a well-established surveillance scheme. RESULTS: The prematurity rate (< 37 weeks gestation) was higher in women on highly active antiretroviral therapy (HAART) (14.1%, 476/3384) than in women on mono/dual therapy (10.1%, 107/1061), even after adjusting for ethnicity, maternal age, clinical status and injecting drug use as the source of HIV acquisition [adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI), 1.19-1.93; P = 0.001]. Delivery at < 35 weeks was even more strongly associated with HAART (AOR = 2.34; 95% CI, 1.64-3.37; P < 0.001). The effect was the same whether or not HAART included a protease inhibitor. In comparison with exposure to mono/dual therapy, exposure to HAART was associated with lower birthweight standardized for gestational age (P < 0.001), and an increased risk of stillbirth (AOR = 2.27; 95% CI, 0.96-5.41; P = 0.063). CONCLUSIONS: These findings, based on comprehensive population surveillance, demonstrate an increased risk of prematurity associated with HAART, and a possible association with other perinatal outcomes, including stillbirth and birthweight. Although the beneficial effects of antiretroviral therapy on mother-to-child transmission are indisputable, monitoring antiretroviral therapy in pregnancy remains a priority.

Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study.

BACKGROUND: Convulsive status epilepticus is the most common childhood medical neurological emergency, and is associated with significant morbidity and mortality. Most data for this disorder are from mainly adult populations and might not be relevant to childhood. Thus we undertook the North London Status Epilepticus in Childhood Surveillance Study (NLSTEPSS): a prospective, population-based study of convulsive status epilepticus in childhood, to obtain a uniquely paediatric perspective. METHODS: Clinical and demographic data for episodes of childhood convulsive status epilepticus that took place in north London were obtained through a clinical network that covered the target population. We obtained these data from anonymised copies of a standardised admission proforma; accident and emergency, nursing, ambulance, and intensive-care unit notes; and interviews with parents, medical, nursing, and paramedic staff. We investigated ascertainment using capture-recapture modelling. FINDINGS: Of 226 children enrolled, 176 had a first ever episode of convulsive status epilepticus. We estimated that ascertainment was between 62% and 84%. The ascertainment-adjusted incidence was between 17 and 23 episodes per 100,000 per year. 98 (56%, 95% CI 48-63) children were neurologically healthy before their first ever episode and 56 (57%, 47-66) of those children had a prolonged febrile seizure. 11 (12%, 6-18) of children with first ever febrile convulsive status epilepticus had acute bacterial meningitis. Conservative estimation of 1-year recurrence of convulsive status epilepticus was 16% (10-24%). Case fatality was 3% (2-7%). INTERPRETATION: Convulsive status epilepticus in childhood is more common, has a different range of causes, and a lower risk of death than that in adults. These paediatric data will help inform management of convulsive status epilepticus and appropriate allocation of resources to reduce the effects of this disorder in childhood.

The Roles of PAX6 and SOX2 in Myopia: lessons from the 1958 British Birth Cohort.

PURPOSE: Myopia is a common complex trait that affects up to 60% of some populations. Its development is influenced by multiple genes and environmental factors. PAX6 and SOX2 are genes with fundamental roles in ocular growth and development, and they have been linked with myopia in a recent linkage study. The authors investigated the roles of PAX6 and SOX2 in common myopia as part of a broader association study of refractive error. METHODS: Five hundred ninety-six persons from the 1958 British Birth Cohort, a nationally representative population, were randomly selected from the outer tertiles of the refractive error (RE) distribution and were genotyped using 25 tagSNPs across PAX6 and 3 tagSNPs across SOX2 and their putative control regions. This experiment had 80% power to exclude either gene contributing more than 10% of the variance of refractive error. RESULTS: All SNPs were in Hardy-Weinberg equilibrium, and the genotyping failure rate was less than 5%. Accounting for multiple testing, no significant association (P < 0.05) was found between any of the SNPs or haplotypes and refractive error. CONCLUSIONS: PAX6 and SOX2 are obvious candidates in RE genetic studies because of their biological roles and prior linkage studies. The present findings strongly suggest refractive error is not directly affected in this population by variants in either gene or by their known promoters/enhancers. The authors suggest that neither PAX6 nor SOX2 should be prioritized in the international search for genetic modifiers of refractive error. Their findings contribute to broader understanding of the pathophysiology of refractive error and highlight the critical role of replication in genetic research on complex disorders.

Inferring myopia over the lifecourse from uncorrected distance visual acuity in childhood.

AIM: To report the usefulness of uncorrected distance visual acuity (DVA) at 16 years to "screen" for myopia status and to assess the lifetime risk of myopia, based on a national birth cohort. METHODS: 1867 members of the 1958 British birth cohort for whom there were data on acuity at 16 years had autorefraction, as part of a biomedical survey, at 45 years. Reduced uncorrected DVA at age 16 years (6/12 or worse in both eyes) was compared with adult refraction (spherical equivalent). RESULTS: Only a quarter of individuals in the population studied who had developed myopia by 45 years of age had reduced acuity at 16 years of age. Notably, half of all adults with moderate myopia (-2.99 to -5.99) and 31% (11/35) with severe myopia (> or =-6) had good uncorrected DVA in both eyes at 16 years of age. Thus, sensitivities were low, ranging from 16% for all myopia (cut-off point spherical equivalent -0.5) to 69% for severe myopia (cut-off point spherical equivalent -6). However, a high (91%) lifetime probability of primary myopia (spherical equivalent > or =-0.5) given a reduced uncorrected DVA at 16 years was found. CONCLUSION: In this population, reduced uncorrected DVA in childhood is an inaccurate and inappropriate intermediate "phenotype" for capturing adult myopia status. However, our findings support assessment of DVA in secondary school children as an effective method of identifying refractive error (both myopia and hypermetropia).