Receiving Palliative Treatment Moderates the Effect of Age and Gender on Demoralization in Patients with Cancer

Background

Existential distress is an important factor affecting psychological well-being in cancer patients. We studied occurrence and predictors of demoralization, a syndrome of existential distress, in particular the interaction of age, gender, and curative vs. palliative treatment phase.

Methods

A cross-sectional sample of N = 750 patients with different tumor sites was recruited from in- and outpatient treatment facilities. Patients completed the following self-report questionnaires: Demoralization Scale, Patient Health Questionnaire-9, Illness-Specific Social Support Scale Short Version-8, and physical problems list of the NCCN Distress Thermometer. Moderated multiple regression analyses were conducted.

Results

We found high demoralization in 15% and moderate demoralization in 8% of the sample. Curative vs. palliative treatment phase moderated the impact of age and gender on demoralization (three-way interaction: b = 1.30, P = .02): the effect of age on demoralization was negative for women receiving palliative treatment (b = −.26, P = .02) and positive for men receiving palliative treatment (b = .25, P = .03). Effects of age and gender were not significant among patients receiving curative treatment. Female gender was associated with higher demoralization among younger patients receiving palliative treatment only. Analyses were controlled for significant effects of the number of physical problems (b = 6.10, P<.001) and social support (b = −3.17, P<.001).

Conclusions

Existential distress in terms of demoralization is a relevant problem within the spectrum of cancer-related distress. It is associated with a complex interaction of demographic and medical patient characteristics; existential challenges related to palliative treatment may exacerbate the impact of age- and gender-related vulnerability factors on demoralization. Psychosocial interventions should acknowledge this interaction in order to address the individual nature of existential distress in subgroups of cancer patients.     

Impact of Community-Based Maternal Health Workers on Coverage of Essential Maternal Health Interventions among Internally Displaced Communities in Eastern Burma: The MOM Project

Background

Access to essential maternal and reproductive health care is poor throughout Burma, but is particularly lacking among internally displaced communities in the eastern border regions. In such settings, innovative strategies for accessing vulnerable populations and delivering basic public health interventions are urgently needed.

Methods

Four ethnic health organizations from the Shan, Mon, Karen, and Karenni regions collaborated on a pilot project between 2005 and 2008 to examine the feasibility of an innovative three-tiered network of community-based providers for delivery of maternal health interventions in the complex emergency setting of eastern Burma. Two-stage cluster-sampling surveys among ever-married women of reproductive age (15–45 y) conducted before and after program implementation enabled evaluation of changes in coverage of essential antenatal care interventions, attendance at birth by those trained to manage complications, postnatal care, and family planning services.

Results

Among 2,889 and 2,442 women of reproductive age in 2006 and 2008, respectively, population characteristics (age, marital status, ethnic distribution, literacy) were similar. Compared to baseline, women whose most recent pregnancy occurred during the implementation period were substantially more likely to receive antenatal care (71.8% versus 39.3%, prevalence rate ratio [PRR] = 1.83 [95% confidence interval (CI) 1.64–2.04]) and specific interventions such as urine testing (42.4% versus 15.7%, PRR = 2.69 [95% CI 2.69–3.54]), malaria screening (55.9% versus 21.9%, PRR = 2.88 [95% CI 2.15–3.85]), and deworming (58.2% versus 4.1%, PRR = 14.18 [95% CI 10.76–18.71]. Postnatal care visits within 7 d doubled. Use of modern methods to avoid pregnancy increased from 23.9% to 45.0% (PRR = 1.88 [95% CI 1.63–2.17]), and unmet need for contraception was reduced from 61.7% to 40.5%, a relative reduction of 35% (95% CI 28%–40%). Attendance at birth by those trained to deliver elements of emergency obstetric care increased almost 10-fold, from 5.1% to 48.7% (PRR = 9.55 [95% CI 7.21–12.64]).

Conclusions

Coverage of maternal health interventions and higher-level care at birth was substantially higher during the project period. The MOM Project''s focus on task-shifting, capacity building, and empowerment at the community level might serve as a model approach for similarly constrained settings. Please see later in the article for the Editors'' Summary     

Hirsch Index and Truth Survival in Clinical Research

Background

Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. We hypothesized that publications with a first author having a higher Hirsch'' index value (h-I), which quantifies and predicts an individual''s scientific research output, should have a longer half-life.

Methods and Results

474 original articles concerning cirrhosis or hepatitis published from 1945 to 1999 were selected. The survivals of the main conclusions were updated in 2009. The truth survival was assessed by time-dependent methods (Kaplan Meier method and Cox). A conclusion was considered to be true, obsolete or false when three or more observers out of the six stated it to be so. 284 out of 474 conclusions (60%) were still considered true, 90 (19%) were considered obsolete and 100 (21%) false. The median of the h-I was = 24 (range 1–85). Authors with true conclusions had significantly higher h-I (median = 28) than those with obsolete (h-I = 19; P = 0.002) or false conclusions (h-I = 19; P = 0.01). The factors associated (P<0.0001) with h-I were: scientific life (h-I = 33 for>30 years vs. 16 for<30 years), -methodological quality score (h-I = 36 for high vs. 20 for low scores), and -positive predictive value combining power, ratio of true to not-true relationships and bias (h-I = 33 for high vs. 20 for low values). In multivariate analysis, the risk ratio of h-I was 1.003 (95%CI, 0.994–1.011), and was not significant (P = 0.56). In a subgroup restricted to 111 articles with a negative conclusion, we observed a significant independent prognostic value of h-I (risk ratio = 1.033; 95%CI, 1.008–1.059; P = 0.009). Using an extrapolation of h-I at the time of article publication there was a significant and independent prognostic value of baseline h-I (risk ratio = 0.027; P = 0.0001).

Conclusions

The present study failed to clearly demonstrate that the h-index of authors was a prognostic factor for truth survival. However the h-index was associated with true conclusions, methodological quality of trials and positive predictive values.     

Crohn's Disease and Early Exposure to Domestic Refrigeration

Background

Environmental risk factors playing a causative role in Crohn''s Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.

Methodology/Principal Findings

Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01–4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.

Conclusion

This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.     

Quality of DNA Extracted from Mouthwashes

Background

A cost effective, safe and efficient method of obtaining DNA samples is essential in large scale genetic analyses. Buccal cells are an attractive source of DNA, as their collection is non-invasive and can be carried out by mail. However, little attention has been given to the quality of DNA extracted from mouthwashes.

Methodology

Mouthwash-derived DNA was extracted from 500 subjects participating in a genetic study of high myopia. DNA quality was investigated using two standard techniques: agarose gel electrophoresis and quantitative polymerase chain reaction (qPCR).

Principal Findings

Whereas the majority of mouthwash-derived DNA samples showed a single band of high molecular weight DNA by gel electrophoresis, 8.9% (95% CI: 7.1–10.7%) of samples contained only a smear of low-to-medium molecular weight, degraded DNA. The odds of DNA degradation in a subject''s second mouthwash sample, given degradation of the first, was significantly greater than one (OR = 3.13; 95% CI: 1.22–7.39; Fisher''s test P = 0.009), suggesting that DNA degradation was at least partially a subject-specific phenomenon. Approximately 12.4% (95% CI: 10.4–14.4%) of mouthwash-derived DNA failed to PCR amplify efficiently (using an ∼200 bp microsatellite marker). However, we found there was no significant difference in amplification success rate between DNA samples judged to be degraded or non-degraded by gel electrophoresis (Fisher''s test P = 0.5).

Conclusions

This study demonstrated that DNA degradation affects a significant minority of saline mouthwashes, and that the phenomenon is partially subject-specific. Whilst the level of degradation did not significantly prevent successful amplification of short PCR fragments, previous studies suggest that such DNA degradation would compromise more demanding applications.     

Family Practices' Achievement of Diabetes Quality of Care Targets and Risk of Screen-Detected Diabetic Retinopathy

Background

We aimed to determine whether family practices'' achievement of diabetes quality of care targets is associated with diabetic retinal disease in registered patients.

Methods

Data for achievement of diabetes quality of care targets, including the proportion of patients with HbA1c≤7.5%, for 144 family practices in London UK, for the years 2004/5 to 2007/8, were linked to data from a population-based diabetes eye screening programme collected from September 2007 to February 2009. Analyses were adjusted for age, sex, duration and type of diabetes, unadjusted diabetes prevalence, ethnicity and deprivation category.

Results

Data were analysed for 24,458 participants with one or more eye screening results in the period. There were 9,332 (38%) with any diabetic retinopathy and 2,819 (11.5%) with sight threatening diabetic retinopathy (STDR), including 2,654 (10.9%) with maculopathy. Among participants registered at 13 family practices that were in the highest quartile for achievement of the HbA1c quality of care target for all four years of study, the relative odds of any diabetic retinopathy were 0.78 (0.69 to 0.88) P<0.001. For participants at 12 practices consistently in the lowest quartile of HbA1c achievement, the relative odds of any diabetic retinopathy were 1.16 (1.03 to 1.30), P = 0.015. In the highest achieving practices, the relative odds of maculopathy were 0.74 (0.62 to 0.89), P = 0.001 and STDR 0.77 (0.65 to 0.92), P = 0.004.

Conclusions

The risk of diabetic retinopathy might be lower at family practices that consistently achieve highly on diabetes quality of care targets for HbA1c.     

Screening for Autism Spectrum Disorders with the Brief Infant-Toddler Social and Emotional Assessment

Objective

Using parent-completed questionnaires in (preventive) child health care can facilitate the early detection of psychosocial problems and psychopathology, including autism spectrum disorders (ASD). A promising questionnaire for this purpose is the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). The screening accuracy with regard to ASD of the BITSEA Problem and Competence scales and a newly calculated Autism score were evaluated.

Method

Data, that was collected between April 2010 and April 2011, from a community sample of 2-year-olds (N = 3127), was combined with a sample of preschool children diagnosed with ASD (N = 159). For the total population and for subgroups by child''s gender, area under the Receiver Operating Characteristic (ROC) curve was examined, and across a range of BITSEA Problem, Competence and Autism scores, sensitivity, specificity, positive and negative likelihood ratio''s, diagnostic odds ratio and Youden''s index were reported.

Results

The area under the ROC curve (95% confidence interval, [95%CI]) of the Problem scale was 0.90(0.87–0.92), of the Competence scale 0.93(0.91–0.95), and of the Autism score 0.95(0.93–0.97). For the total population, the screening accuracy of the Autism score was significantly better, compared to the Problem scale. The screening accuracy of the Competence scale was significantly better for girls (AUC = 0.97; 95%CI = 0.95–0.98) than for boys (AUC = 0.91; 95%CI = 0.88–0.94).

Conclusion

The results indicate that the BITSEA scales and newly calculated Autism score have good discriminative power to differentiate children with and without ASD. Therefore, the BITSEA may be helpful in the early detection of ASD, which could have beneficial effects on the child''s development.     

Effectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1 in Routine Public Health Services in Cameroon

Background

Multidrug antiretroviral (ARV) regimens including HAART and short-course dual antiretroviral (sc-dARV) regimens were introduced in 2004 to improve Prevention of Mother-to-Child Transmission (PMTCT) in Cameroon. We assessed the effectiveness of these regimens from 6–10 weeks and 12 months of age, respectively.

Methodology/Findings

We conducted a retrospective cohort study covering the period from October 2004 to March 2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 ≤350 cells/mm³ received first-line HAART [regimen 1] while the others received ARV prophylaxis including sc-dARV or single dose nevirapine (sd-NVP). Sc-dARV included at least two drugs according to different gestational ages: zidovudine (ZDV) from 28–32 weeks plus sd-NVP [regimen 2], ZDV and lamuvidine (3TC) from 33–36 weeks plus sd-NVP [regimen 3]. When gestational age was ≥37 weeks, women received sd-NVP during labour [regimen 4]. Infants received sd-NVP plus ZDV and 3TC for 7 days or 30 days. Early diagnosis (6–10 weeks) was done, using b-DNA and subsequently RT-PCR. We determined early MTCT rate and associated risk factors using logistic regression. The 12-month HIV-free survival was assessed using Cox regression. Among 418 mothers, 335 (80%) received multidrug ARV regimens (1, 2, and 3) and MTCT rate with multidrug regimens was 6.6% [95%CI: 4.3–9.6] at 6 weeks, without any significant difference between regimens. Duration of mother''s ARV regimen <4 weeks [OR = 4.7, 95%CI: 1.3–17.6], mother''s CD4 <350 cells/mm³ [OR = 6.4, 95%CI: 1.8–22.5] and low birth weight [OR = 4.0, 95%CI: 1.4–11.3] were associated with early MTCT. By 12 months, mixed feeding [HR = 8.7, 95%CI: 3.6–20.6], prematurity [HR = 2.3, 95%CI: 1.2–4.3] and low birth weight were associated with children''s risk of progressing to infection or death.

Conclusions

Multidrug ARV regimens for PMTCT are feasible and effective in routine reference hospital. Early initiation of ARV during pregnancy and proper obstetrical care are essential to improve PMTCT.     

The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies

Background

Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications.

Methods and Findings

A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06–2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89–1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80–1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79–1.99) or SGA (OR 1.25, 95% CI 0.92–1.70).

Conclusions

Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants. Please see later in the article for the Editors'' Summary     

Residential Selection across the Life Course: Adolescent Contextual and Individual Determinants of Neighborhood Disadvantage in Mid-Adulthood

Background

Numerous cross-sectional studies have examined neighborhood effects on health. Residential selection in adulthood has been stressed as an important cause of selection bias but has received little empirical attention, particularly its determinants from the earlier life course. The present study aims to examine whether neighborhood, family, school, health behaviors and health in adolescence are related to socioeconomic disadvantage of one''s neighborhood of residence in adulthood.

Methods

Based on the prospective Northern Swedish Cohort (analytical N = 971, 90.6% retention rate), information was collected at age 16 years concerning family circumstances, school adjustment, health behaviors and mental and physical health. Neighborhood register data was linked to the cohort and used to operationalize aggregated measures of neighborhood disadvantage (ND) at age 16 and 42. Data was analyzed with linear mixed models, with ND in adulthood regressed on adolescent predictors and neighborhood of residence in adolescence as the level-2 unit.

Results

Neighborhood disadvantage in adulthood was clustered by neighborhood of residence in adolescence (ICC = 8.6%). The clustering was completely explained by ND in adolescence. Of the adolescent predictors, ND (b = .14 (95% credible interval = .07–.22)), final school marks (b = −.18 (−.26–−.10)), socioeconomic disadvantage (b = .07 (.01–.14)), and, with borderline significance, school peer problems (b = .07 (−.00–.13)), were independently related to adulthood ND in the final adjusted model. In sex-stratified analyses, the most important predictors were school marks (b = −.21 (−.32–−.09)) in women, and neighborhood of residence (ICC = 15.5%) and ND (b = .20 (.09–.31)) in men.

Conclusions

These findings show that factors from adolescence – which also may impact on adult health – could influence the neighborhood context in which one will live in adulthood. This indicates that residential selection bias in neighborhood effects on health research may have its sources in early life.     

Bacterial Load of Pneumococcal Serotypes Correlates with Their Prevalence and Multiple Serotypes Is Associated with Acute Respiratory Infections among Children Less Than 5 Years of Age

Background

Among pneumococcal serotypes, some serotypes are more prevalent in the nasopharynx than others; determining factors for higher prevalence remain to be fully explored. As non-vaccine serotypes have emerged after the introduction of 7-valent conjugate vaccines, study of serotype specific epidemiology is in need. When two or more serotypes co-colonize, they evolve rapidly to defend host''s immune responses; however, a clear association of co-colonization with a clinical outcome is lacking.

Methods

Children less than 5 years old who were admitted to hospital due to acute respiratory infections (ARI) (n = 595) and healthy children (n = 350) were recruited. Carriage of pneumococcus was determined by culture and lytA PCR in the nasopharyngeal samples. Serotype/serogroup detection and its quantification were done by the nanofluidic real time PCR system. Spearman''s correlation and logistic regression were used to examine a correlation of serotype/serogroup specific bacterial load with its prevalence and an association of co-colonization with ARI respectively.

Results

Serotype/serogroup specific bacterial load was correlated with its prevalence, both in ARI cases (Spearman''s rho = 0.44, n = 186; P<0.0001) and healthy children (Spearman''s rho = 0.41, n = 115; P<0.0001). The prevalence of multiple serotypes was more common in ARI cases than in healthy children (18.5% vs 7.1%; aOR 2.92, 95% CI: 1.27–6.71; P = 0.01). The dominant serotype in the co-colonization had a 2 log10 higher bacterial load than the subdominant serotype, both in ARI cases (P<0.001) and healthy children (P<0.05).

Conclusions

High bacterial load in the nasopharynx may help transmit pneumococci among hosts, and increase the chance of successful acquisition and colonization. Co-colonization of multiple serotypes of pneumococci is linked with ARI, which infers the interactions of multiple serotypes may increase their pathogenicity; however, they may compete for growth in number.     

Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years

Background

Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.

Methods

In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ).

Results

Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = −2.69 (95% confidence interval [CI] = −4.33, −1.05) and b = −2.69 (95% CI = −4.22, −1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4) and 7.6 (95% CI = 3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.

Conclusion

Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children’s intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.     

Knowledge of Malaria and Its Association with Malaria-Related Behaviors—Results from the Malaria Indicator Survey,Ethiopia, 2007

Background

In 2005, the Ministry of Health in Ethiopia launched a major effort to distribute over 20 million long-lasting insecticidal nets, provide universal access to artemisinin-based combination therapy (ACTs), and train 30,000 village-based health extension workers.

Methods and Findings

A cross-sectional, nationally representative Malaria Indicator Survey was conducted during the malaria transmission season in 2007. Multivariate logistic regression analyses were performed to assess the effect of women''s malaria knowledge on household ITN ownership and women''s ITN use. In addition, we investigated the effect of mothers'' malaria knowledge on their children under 5 years of age''s (U5) ITN use and their access to fever treatment on behalf of their child U5. Malaria knowledge was based on a composite index about the causes, symptoms, danger signs and prevention of malaria. Approximately 67% of women (n = 5,949) and mothers of children U5 (n = 3,447) reported some knowledge of malaria. Women''s knowledge of malaria was significantly associated with household ITN ownership (adjusted Odds Ratio [aOR] = 2.1; 95% confidence interval [CI] 1.6–2.7) and with increased ITN use for themselves (aOR = 1.8; 95% CI 1.3–2.5). Knowledge of malaria amongst mothers of children U5 was associated with ITN use for their children U5 (aOR = 1.6; 95% CI 1.1–2.4), but not significantly associated with their children U5 seeking care for a fever. School attendance was a significant factor in women''s ITN use (aOR = 2.0; 95% CI 1.1–3.9), their children U5′s ITN use (aOR = 4.4; 95% CI 1.6–12.1), and their children U5 having sought treatment for a fever (aOR = 6.5; 95% CI 1.9–22.9).

Conclusions

Along with mass free distribution of ITNs and universal access to ACTs, delivery of targeted malaria educational information to women could improve ITN ownership and use. Efforts to control malaria could be influenced by progress towards broader goals of improving access to education, especially for women.     

Cognitive Function in Adult Offspring of Women with Gestational Diabetes–The Role of Glucose and Other Factors

Objective

We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.

Materials and Methods

In 2003–2005 cognitive function was assessed in a cohort of 18–27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153) and offspring from the background population (n = 118). The main outcome measure was global cognitive score derived from Raven’s Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. Maternal fasting- and 2-hour blood glucose values from the diagnostic oral glucose tolerance test were used as exposure variables.

Results

Offspring of women with gestational diabetes mellitus had a lower global cognitive score, than offspring from the background population (93.1 vs. 100.0, P<0.001). However, when adjusted for maternal age at delivery, parity, smoking during pregnancy, pre-pregnancy overweight, family social class, parental educational level, gender, birth weight, gestational age, perinatal complications and offspring age at follow-up, the difference was no longer statistically significant. Offspring global cognitive score decreased significantly with increasing maternal fasting glucose (β = −4.5, 95% CI −8.0 to −0.9, P = 0.01) and 2-hour glucose (β = −1.5, −2.9 to −0.2, P = 0.03) in univariate general linear models, but not when adjusted for family social class and parental educational level.

Conclusions

Lower cognitive test scores in adult offspring of women with diet-treated gestational diabetes were explained by well known predictors of cognitive function, but not by maternal hyperglycaemia during pregnancy. We find it reassuring that mild intrauterine hyperglycaemia does not seem to have adverse effect on offspring cognitive function.     

Traits Contributing to the Autistic Spectrum

Background

It is increasingly recognised that traits associated with autism reflect a spectrum with no clear boundary between typical and atypical behaviour. Dimensional traits are needed to investigate the broader autism phenotype.

Methods and Principal Findings

Ninety-three individual measures reflecting components of social, communication and repetitive behaviours characterising autistic spectrum disorder (ASD) were identified between the ages of 6 months and 9 years from the ALSPAC database. Using missing value imputation, data for 13,138 children were analysed. Factor analysis suggested the existence of 7 factors explaining 85% of the variance. The factors were labelled: verbal ability, language acquisition, social understanding, semantic-pragmatic skills, repetitive-stereotyped behaviour, articulation and social inhibition. Four factors (1, 3, 5 and 7) were specific to ASD being more strongly associated with this phenotype than other co-morbid conditions while other factors were more associated with learning difficulties and specific language impairment. Nevertheless, all 7 factors contributed independently to the explanation of ASD (p<0.001). Exploration of putative genetic causal factors such as variants in the CNTNAP2 gene showed a varying pattern of associations with these traits. An alternative predictive model of ASD was derived using four individual measures: the coherence subscale of the Children''s Communication Checklist (9y), the Social and Communication Disorders Checklist (91 m), repetitive behaviour (69 m) and the sociability subscale of the Emotionality Activity and Sociability measure (38 m). Although univarably these traits performed better than some factors, their combined explanations of ASD were similar (R² = 0.48).

Conclusions and Significance

These results support the fractional nature of ASD with different aetiological origins for these components despite pleiotropic genetic effects being observed. These traits are likely to be useful in the exploration of ASD.     

High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development

Background

Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years.

Methods

From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids.

Results

The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P<0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18∶1n-9 as well as total MUFA (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (P_trend<0.001), n-6 LCPUFA (P_trend = 0.001), and total LCPUFA (P_trend<0.001) and decreased linearly with the proportions of total MUFA (P_trend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy.

Conclusion

A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant''s immune system.     

Unhealthy Days and Quality of Life in Irish Patients with Diabetes

Objectives

To study the determinants of health-related quality of life (HRQoL) in Irish patients with diabetes using the Centres for Disease Controls'' (CDC''s) ‘Unhealthy Days’ summary measure and to assesses the agreement between this generic HRQoL measure and the disease-specific Audit of Diabetes Dependant Quality of Life (ADDQoL) measure.

Research Design and Methods

Data were analysed from the Diabetes Quality of Life Study, a cross-sectional study of 1,456 people with diabetes in Ireland (71% response rate). Unhealthy days were assessed using the CDC''s ‘Unhealthy days’ summary measure. Quality of life (QoL) was also assessed using the ADDQoL measure. Analyses were conducted primarily using logistic regression. The agreement between the two QoL instruments was measured using the kappa co-efficient.

Results

Participants reported a median of 2 unhealthy days per month. In multivariate analyses, female gender (P = 0.001), insulin use (P = 0.030), diabetes complications (P = <0.001) were significantly associated with more unhealthy days. Older patients had fewer unhealthy days per month (P = 0.003). Agreement between the two measures of QoL (unhealthy days measure and ADDQoL) was poor, Kappa = 0.234

Conclusions

The findings highlight the determinants of HRQoL in patients with diabetes using a generic HRQoL summary measure. The ‘Unhealthy Days’ and the ADDQoL have poor agreement, therefore the ‘Unhealthy Days’ summary measure may be assessing a different construct. Nonetheless, this study demonstrates that the generic ‘Unhealthy Days’ summary measure can be used to detect determinants of HRQoL in patients with diabetes.     

The Impact of National Institutes of Health Funding on U.S. Cardiovascular Disease Research

Background

Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear.

Methods

The National Library of Medicine''s PubMed database was searched for articles published from 1996 to 2006, originating from U.S. institutions, and containing the phrases “cardiolog,” “cardiovascular,” or “cardiac,” in the first author''s department. Research methodology, journal of publication, journal impact factor, and receipt of NIH funding were recorded. Differences in means and trends were tested with t-tests and linear regression, respectively, with P≤0.05 for significance.

Results

Of 117,643 world cardiovascular articles, 36,684 (31.2%) originated from the U.S., of which 10,293 (28.1%) received NIH funding. The NIH funded 40.1% of U.S. basic science articles, 20.3% of overall clinical trials, 18.1% of randomized-controlled, and 12.2% of multicenter clinical trials. NIH-funded and total articles grew significantly (65 articles/year, P<0.001 and 218 articles/year, P<0.001, respectively). The proportion of articles receiving NIH funding was stable, but grew significantly for basic science and clinical trials (0.87%/year, P<0.001 and 0.67%/year, P = 0.029, respectively). NIH-funded articles had greater journal impact factors than non NIH-funded articles (5.76 vs. 3.71, P<0.001).

Conclusions

NIH influence on U.S. cardiovascular research expanded in the past decade, during the period of NIH budget doubling. A substantial fraction of research is now directly funded and thus likely sensitive to budget fluctuations, particularly in basic science research. NIH funding predicts greater journal impact.