Kathryn Fitzpatrick

Reappraisal of known malaria resistance loci in a large multicenter study

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10−4 with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

The management and outcomes of placenta accreta, increta, and percreta in the UK: a population-based descriptive study

To describe the management and outcomes of placenta accreta, increta, and percreta in the UK.

Incidence and risk factors for placenta accreta/increta/percreta in the UK: a national case-control study.

Background Placenta accreta/increta/percreta is associated with major pregnancy complications and is thought to be becoming more common. The aims of this study were to estimate the incidence of placenta accreta/increta/percreta in the UK and to investigate and quantify the associated risk factors. Methods A national case-control study using the UK Obstetric Surveillance System was undertaken, including 134 women diagnosed with placenta accreta/increta/percreta between May 2010 and April 2011 and 256 control women. Results The estimated incidence of placenta accreta/increta/percreta was 1.7 per 10,000 maternities overall; 577 per 10,000 in women with both a previous caesarean delivery and placenta praevia. Women who had a previous caesarean delivery (adjusted odds ratio (aOR) 14.41, 95%CI 5.63–36.85), other previous uterine surgery (aOR 3.40, 95%CI 1.30–8.91), an IVF pregnancy (aOR 32.13, 95%CI 2.03–509.23) and placenta praevia diagnosed antepartum (aOR 65.02, 95%CI 16.58–254.96) had raised odds of having placenta accreta/increta/percreta. There was also a raised odds of placenta accreta/increta/percreta associated with older maternal age in women without a previous caesarean delivery (aOR 1.30, 95%CI 1.13–1.50 for every one year increase in age). Conclusions Women with both a prior caesarean delivery and placenta praevia have a high incidence of placenta accreta/increta/percreta. There is a need to maintain a high index of suspicion of abnormal placental invasion in such women and preparations for delivery should be made accordingly.

Uterine Rupture by Intended Mode of Delivery in the UK: A National Case-Control Study

A case-control study using UK data estimates the risk of uterine rupture in subsequent deliveries amongst women who have had a previous caesarean section.

Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study

PURPOSE To estimate the prevalence of early and late age-related macular degeneration (AMD) in India. METHODS Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System. RESULTS Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8-1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2-41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8-7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1-0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4-4.7); and early AMD: grade 1, 43.1(35.7-50.6); grade 2, 8.1 (4.3-12.0); and grade 3, 0.5 (0-1.5). CONCLUSIONS The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated.

Prevalence of Cataract in an Older Population in India: The India Study of Age-related Eye Disease

Purpose To describe the prevalence of cataract in older people in 2 areas of north and south India. Design Population-based, cross-sectional study. Participants Randomly sampled villages were enumerated to identify people aged ≥60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination. Methods The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III). Main Outcome Measures Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract. Results The prevalence of unoperated cataract in people aged ≥60 was 58% in north India (95% CI, 56–60) and 53% (95% CI, 51–55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46–50) in north India and 38% (95% CI, 37–40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20–23) and 17% (95% CI, 16–19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7–9) and 10.2% (95% CI, 9–11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002). Conclusions We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Inverse Association of Vitamin C with Cataract in Older People in India

Objective To examine the association between vitamin C and cataract in the Indian setting. Design Population-based cross-sectional analytic study. Participants A total of 5638 people aged ≥60 years. Methods Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography. Main Outcome Measures Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract. Results Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51–0.74; P=1.1×10−6). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57–0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54–0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54–0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45–0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract. Conclusions We found a strong association with vitamin C and cataract in a vitamin C–depleted population. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case-control study.

To describe the incidence, risk factors, management and outcomes of amniotic‐fluid embolism (AFE) over time.

Risk factors, management, and outcomes of hemolysis, elevated liver enzymes, and low platelets syndrome and elevated liver enzymes, low platelets syndrome.

OBJECTIVE: To describe the risk factors, management and outcomes of hemolysis, elevated liver enzymes, and low platelets (HELLP) and elevated liver enzymes, low platelets (ELLP) syndrome in the United Kingdom. METHODS: A case–control study was conducted using the U.K. Obstetric Surveillance System between June 2011 and May 2012, including 129 women diagnosed with HELLP, 81 diagnosed with ELLP, and 476 control women. RESULTS: Women with HELLP were more likely than those in the control group to be 35+ years old (33% compared with 22%, adjusted odds ratio [OR] 1.85, 95% confidence interval [CI] 1.12–3.06), nulliparous (67% compared with 43%, adjusted OR 4.16, 95% CI 2.48–6.98), have had a previous gestational hypertensive disorder (9% compared with 7%, adjusted OR 3.47, 95% CI 1.49–8.09), and have a multiple pregnancy (7% compared with 2%, adjusted OR 4.51, 95% CI 1.45–14.06). Women with ELLP were more likely than those in the control group to be nulliparous (79% compared with 43%, adjusted OR 8.35, 95% CI 3.88–17.95), and have had a previous gestational hypertensive disorder (7% compared with 7%, adjusted OR 4.66, 95% CI 1.37–15.89). Of the women diagnosed antenatally with HELLP or ELLP, 51% (71/138) had planned management of immediate delivery, 43% (60/138) had delivery planned within 48 hours, and 5% (7/138) had planned expectant (conservative) management. No differences were found between women who had delivery planned within 48 hours and those who had planned immediate delivery in terms of the proportion who received blood products (37% compared with 33%, P=.681); were admitted to the intensive care unit (57% compared with 61%, P=.652); experienced severe morbidity (10% compared with 4%, P=.300); or had a neonate with major complications (6% compared with 11%, P=.342). CONCLUSION: A short delay in the delivery of women diagnosed antenatally with HELLP or ELLP syndrome may be considered. However, the rarity of the condition limits study power. LEVEL OF EVIDENCE: II

Prevalence and Risk Factors for Vitamin C Deficiency in North and South India: A Two Centre Population Based Study in People Aged 60 Years and Over

Background Studies from the UK and North America have reported vitamin C deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are few data on vitamin C deficiency in resource poor countries. Objectives To investigate the prevalence of vitamin C deficiency in India. Design We carried out a population-based cross-sectional survey in two areas of north and south India. Randomly sampled clusters were enumerated to identify people aged 60 and over. Participants (75% response rate) were interviewed for tobacco, alcohol, cooking fuel use, 24 hour diet recall and underwent anthropometry and blood collection. Vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid. We categorised vitamin C status as deficient (<11 µmol/L), sub-optimal (11–28 µmol/L) and adequate (>28 µmol/L). We investigated factors associated with vitamin C deficiency using multivariable Poisson regression. Results The age, sex and season standardized prevalence of vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668 people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only 10.8% in the north and 25.9% in the south met the criteria for adequate levels. Vitamin C deficiency varied by season, and was more prevalent in men, with increasing age, users of tobacco and biomass fuels, in those with anthropometric indicators of poor nutrition and with lower intakes of dietary vitamin C. Conclusions In poor communities, such as in our study, consideration needs to be given to measures to improve the consumption of vitamin C rich foods and to discourage the use of tobacco.