Mid-adult Life Research Articles

Long-Term Follow-up of Adults Following the Atrial Switch Operation for Transposition of the Great Arteries – A Contemporary Cohort

The atrial switch operation for transposition of the Great Arteries (TGA) (Mustard or Senning Procedure) provides excellent short-term survival. Significant long-term concerns exist for these patients, however, including the ability of the right ventricle to maintain systemic perfusion and the risk of arrhythmia. We seek to describe long-term mortality and morbidity of this group of adult patients. Consecutive patients who had undergone an atrial switch procedure, who were aged over 16 years and who were followed up at our tertiary level adult congenital heart disease (ACHD) service in Sydney, Australia since 2000 were included. We documented mortality using a National Death Index and analysed the prospectively defined composite endpoint of "Serious Adverse Events" including death, heart failure hospitalisation and/or documented ventricular arrhythmia. There were 83 patients included; mean age at most recent follow-up was 35 ± 5 years. Overall survival was 82% at 35 years and 22% of patients experienced a serious adverse event. Atrial and ventricular arrhythmias occurred in 45% and 7% of patients respectively. Eighteen (22%) patients required a pacemaker and six (7%) required implantable cardiac defibrillator (ICD) implantation. Significant right ventricular dysfunction was present in 26% of patients on their most recent visit and this, or requirement for permanent pacing, was associated with an increased risk of serious adverse events (OR 10.22, p<0.001), (OR 4.998, p=0.04) respectively. Significant mortality and morbidity accrues by mid-adult life after an atrial procedure for TGA. Right ventricular dysfunction and permanent pacing are associated with serious adverse events.

Possible positive effect of the APOE ε2 allele on cognition in early to mid-adult life

Backgroundε4 allele possession is associated with an increased risk of Alzheimer’s disease. Its effects earlier in life are less well understood. Previous studies have reported both detrimental effects and a lack of effect on cognition outside dementia. We used genotype based recall from the ALSPAC study to investigate whether APOE genotype influences cognition in earlier adult life. MethodsWe invited all individuals with the rarer ε22 or ε44 genotypes and equal numbers of those with ε32, ε33 or ε34 APOE genotypes (total n invited = 1936, ages 23–67). Participants were screened for dementia using the Addenbrooke’s Cognitive Examination Revised (ACE-R). Participants were asked to complete a 3 h battery of neuropsychological tests covering a range of cognitive domains. The primary outcome was performance on the Rey Auditory Verbal Learning Test (RAVLT). Transformation of variables was used where required to permit parametric testing. As genotypes are unlikely to be confounded unadjusted analyses were performed. Results114 participants were recruited to the study (39 ε33, 27 ε34, 15 ε44, 26 ε32 & 7 ε22). ε4+ participants had higher scores on the cognitive failures questionnaire (10 point increase, p = 0.006) but no deficits on objective cognitive testing. ε2 carriers had slightly better episodic memory performance (p = 0.016), slightly improved n-back accuracy and better executive functioning (trails A&B, p = 0.005). ConclusionsIt is intriguing that the ε2+ group performed better as this group have a lower risk of Alzheimer’s disease. Most previous studies have analysed as ε4/non ε4 so may have missed this effect.

Pigmented Dermatofibrosarcoma Protuberans (Bednar Tumor) masquerading clinically as malignant melanoma - A Case Report

Bednar tumor is a rare neoplasm of intermediate malignant potential, which account for less than 5% of dermatofibrosarcoma protuberans (DFSP).This tumor is a pigmented variant of DFSP. The diagnosis is commonly made in early to mid adult life except in cases with melanin containing cells. The case report presents a 19 years old female who presented with a painless slow-growing 3.5×3×1.2 cm blackish mass on the dorsal aspect of her right foot. Histopathological examination of the biopsy specimen revealed typical features of a Bednar tumor, the diagnosis was confirmed through immunohistochemical study. DOI: 10.21276/AABS.2017.1279

The employment history of people with and without asthma

Introduction People with asthma may have a greater likelihood of leaving employment due to ill health, spending more time in unemployment and changing jobs more frequently because of their disease. Some studies have reported that people with childhood asthma were disadvantaged in later employment. The aim of this analysis is to investigate the effects of asthma on employment history from early-to mid-adult life (age 42) in a British birth cohort. Methods Members of the National Child Development Study (NCDS) cohort with information on asthma and an employment history from ages 16 to 42 were included (n=9881). Asthma was defined as childhood asthma (0-16), severe childhood asthma, current asthma at age 16 and adult onset asthma. Outcomes were ever having a period out of employment, total periods of employment and unemployment and total time out of employment. The associations between asthma and the outcomes were assessed separately for men and women using Mann-Whitney or Kruskal Wallis tests, with significant results explored using a logistic regression model for binary outcomes and a negative binomial regression model (with a zero inflated model for outcomes with large numbers of zeros) for count data. Results By age 42, 43% of the cohort had experienced at least one period out of employment and the median number of employment periods was 6, with women reporting on average one more job by age 42 than men. Women reporting adult onset asthma were likely to have had more periods of employment when compared to women who never had asthma (p=0.003). For both men and women with adult onset asthma there was a doubling of the risk of ever being out of employment due to ill health compared to those without asthma (men OR 1.94 [95% CI 1.24-3.04], women OR 2.00 [95% CI 1.43-2.80]). Conclusion There is evidence that adult onset (but not childhood) asthma affects employment history, particularly for women. It is not known whether this reflects the experience of more recent cohorts.

The Effect of Cigarette Smoking on Lung Function in Young Adults with Asthma.

Life-course persistent asthma and tobacco smoking are risk factors for irreversible airflow obstruction. It is often assumed that smoking and asthma have additive or multiplicative effects on the risk for airflow obstruction, but this has not been demonstrated in prospective studies of children with persistent asthma. To investigate the effects of smoking and asthma on the development of airflow obstruction in a population-based birth cohort followed to age 38 years. Reports of childhood asthma from ages 9, 11, and 13 and self-reports of adult asthma at ages 32 and 38 years were used to define childhood-onset persistent asthma (n = 91), late-onset asthma (n = 93), asthma in remission (n = 85), and nonasthmatic (n = 572) phenotypes. Cumulative tobacco smoking histories and spirometry were obtained at ages 18, 21, 26, 32, and 38 years. Analyses were by generalized estimating equations adjusting for childhood spirometry, body mass index, age, and sex. Smoking history and childhood-onset persistent asthma were both associated with lower FEV1/FVC ratios. Associations between smoking and FEV1/FVC ratios were different between asthma phenotypes (interaction P < 0.001). Smoking was associated with lower prebronchodilator and post-bronchodilator FEV1/FVC ratios among subjects without asthma and those with late-onset or remittent asthma, but smoking was not associated with lower FEV1/FVC ratios among those with childhood-onset persistent asthma. Childhood-onset persistent asthma is associated with airflow obstruction by mid-adult life, but this does not seem to be made worse by tobacco smoking. We found no evidence that smoking and childhood-persistent asthma have additive or multiplicative effects on airflow obstruction.

Glycemic and non-glycemic targets in younger and older North Indian subjects with type 2 diabetes in a Tertiary care hospital: A 10 year's retrospective data analysis

BackgroundAlthough optimizing glycemic and non-glycemic targets reduced micro- and macro-vascular complications in type 2 diabetes, multiple barriers hinder turning evidence into practice. Mounting evidence suggests that those with onset of disease in early or mid-adult life, compared with those with onset at an older age, may have a more severe disease course and worse glycemic control. Aims & objectiveWe tested the hypothesis that those diagnosed at younger age would have worse glycemic control, even after adjustment for duration of diabetes, higher BMI and other known risk factors for worse glycemic control. Materials & methodsA cross-sectional analysis of 560 type 2 diabetic subjects from North Indian populace in the year 1999–2012 who reported to endocrine clinic was performed. Sixty patients did not report in the successive year and final data analyses were done in 500 patients attending clinic regularly over a period of 10 years for evaluation of glycemic and non-glycemic targets. They were followed up at 3 monthly intervals with all patients undergoing anthropometric measurement (BMI (weight in kg/height in m2), diet and lifestyle advice by a diabetic educator and consultation by endocrinologist. Fasting and postprandial plasma glucose, A1c (3 monthly), besides evaluation of SMBG that was performed in 50% of these patients regularly. Fasting lipids, S. creatinine and microalbuminuria were assessed annually and blood pressure recoding was done at each visit. The treatment was modified as per the investigation reports. We classified age at diabetes diagnosis as younger (<60 years) vs older (≥60 years). The primary outcome of interest was HbA1c ≥9%. Secondary outcomes were HbA1c ≥8% to <9% and HbA1c ≥7% to <8%. ResultsAfter adjustment for sex, duration of diabetes, hyperglycemic medications, BMI, co-morbid conditions, age <60 years at diagnosis remains significantly associated with greater odds of HbA1c ≥9% [OR 0.95(0.84–1.07)], HbA1c ≥8% to <9% [OR 1.04(0.93–1.15)] and HbA1c ≥7% to <8% [OR 1.05(0.85–1.17)] for female sex. Seventy two (72.7%) of patients <60 years achieved BP <140/90mmHg (p<0.001) as compared to 62.3% of patients ≥60 years who achieved BP <150/90mmHg (p<0.001) and LDL-cholesterol <100mg/dl in 33.7% patients and 39.1% respectively (p<0.002). ConclusionYounger age (<60 years) at type 2 diabetes diagnosis is significantly associated with worse subsequent glycemic control and lipid control, as younger patients at diagnosis have fewer competing co-morbidities and complications. As patient-centeredness is a priority in type 2 diabetes care, safe, aggressive and individualized treatment could benefit this higher-risk group.

Childhood maltreatment and BMI trajectories to mid-adult life: follow-up to age 50 y in a British birth cohort.

BackgroundChildhood maltreatment including abuse and neglect has been associated with adult obesity, but evidence on life-course development of obesity or BMI gain is unclear. We aim to establish whether childhood maltreatments are related to obesity or BMI at different life-stages 7y-50y and to identify possible explanations for associations.MethodsChildhood physical, psychological and sexual abuse, neglect and BMI at seven ages were recorded in the 1958 birth cohort (n~15,000). Associations of child maltreatments with BMI at separate ages were tested using linear regression or logistic regression for obesity, and with rate of child-to-adult BMI gain using multilevel models. We adjusted for potential covariates.ResultsAbuse was reported in ~12% of the population. Abuse was not associated with elevated childhood BMI, but adult associations were observed: i.e. the abused had faster child-adult BMI gain than the non-abused; associations were independent of adult covariates. For physical abuse in both genders there was a positive linear association of ~0.006/y zBMI gain with age after adjustment for all covariates. Similarly, there was a linear association of physical abuse with obesity risk: e.g. among females from a low ORadjusted of 0.34 (0.16,0.71) at 7y to 1.67 (1.25,2.24) at 50y. In females faster zBMI gains with age of ~0.0034/y were observed for sexual abuse and increases in obesity risk were faster: from a low ORadjusted of 0.23 (0.06,0.84) at 7y to 1.34 (0.86,2.10) at 50y. Psychological abuse and neglect associations were less consistent.ConclusionsChildhood maltreatment associations with BMI or obesity varied across life: physical and, in females, sexual abuse were associated with faster lifetime BMI gains, which may have detrimental long-term health consequences.

SPG7 mutations are a common cause of undiagnosed ataxia.

Late-onset ataxias are clinically and etiologically diverse. Patients rarely have defining clinical features, and many remain classified as idiopathic, despite extensive clinical, metabolic, and genetic investigations. Here we show that mutations in a gene known to cause hereditary spastic paraplegia ( SPG7 ) are a major cause of unexplained ataxia presenting in mid-adult life.

Association of occupational trajectories with alcohol use disorders in a longitudinal national survey.

We investigated longitudinal associations between occupation and alcohol use disorders (AUDs) across early- to mid-adult life. Longitudinal trajectories of work substantive complexity were constructed by growth mixture modeling of occupational data from the National Longitudinal Survey of Youth 1979 and O*NET work variables. The association between work trajectories and AUDs was modeled adjusting for education. Lower work trajectories were associated with higher AUD prevalence and incidence. Incident AUDs were associated with a subsequent decline in work trajectory class for both high and low initial classes, more strongly in women despite lower overall AUD incidence. Low work trajectory is associated with increased AUD prevalence. Development of an AUD may presage risk of decline in work substantive complexity. These findings suggest reinforcing relations between the development of AUD and occupational course at midlife.

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal expansion of secondary mitochondrial DNA mutations modulating the phenotype, driven by compensatory mitochondrial biogenesis.

P32 Mutations in SPG7 cause chronic progressive external ophthalmoplegia through disordered mtDNA maintenance

P32 Mutations in SPG7 cause chronic progressive external ophthalmoplegia through disordered mtDNA maintenance

P31 Genotypic and phenotypic heterogeneity in adult-onset progressive external ophthalmoplegia (PEO) with mitochondrial DNA instability: a systematic review

P31 Genotypic and phenotypic heterogeneity in adult-onset progressive external ophthalmoplegia (PEO) with mitochondrial DNA instability: a systematic review

Gender and incidence of dementia in the Framingham Heart Study from mid-adult life

BackgroundGender-specific risks for dementia and Alzheimer's disease (AD) starting in midlife remain largely unknown. MethodsProspectively ascertained dementia/AD and cause-specific mortality in Framingham Heart Study (FHS) participants was used to generate 10- to 50-year risk estimates of dementia/AD on the basis of the Kaplan–Meier method (cumulative incidence) or accounting for competing risk of death (lifetime risk [LTR]). ResultsOverall, 777 cases of incident dementia (601 AD) occurred in 7901 participants (4333 women) over 136,266 person-years. Whereas cumulative incidences were similar in women and men, LTRs were higher in women older than 85 years of age. LTR of dementia/AD at age 45 was 1 in 5 in women and 1 in 10 in men. Cardiovascular mortality was higher in men with rate ratios decreasing from approximately 6 at 45 to 54 years of age to less than 2 after age 65. ConclusionSelective survival of men with a healthier cardiovascular risk profile and hence lower propensity to dementia might partly explain the higher LTR of dementia/AD in women.

Construction of Early and Midlife Work Trajectories in Women and Their Association With Birth Weight

We derived trajectories of the substantive complexity (SC) of work across mid-adult life in women and determined their association with term birth weight. SC is a concept that encompasses decision latitude, active learning, and ability to use and expand one's abilities at work. Using occupational data from the National Longitudinal Survey of Youth 1979 and O*NET work variables, we used growth mixture modeling (GMM) to construct longitudinal trajectories of work SC from the ages of 18 to 34 years. The association between work trajectories and birth weight of infants born to study participants was modeled using generalized estimating equations, adjusting for education, income, and relevant covariates. GMM yielded a 5-class solution for work trajectories in women. Higher work trajectories were associated with higher term birth weight and were robust to the inclusion of both education and income. A work trajectory that showed a sharp rise after age 24 years was associated with marked improvement in birth weight. Longitudinal modeling of work characteristics might improve capacity to integrate occupation into a life-course model that examines antecedents and consequences for maternal and child health.

Is There a Role for Acetabular Dysplasia Correction in an Asymptomatic Patient?

Childhood hip dysplasia is best treated in infancy or early childhood with hopes that the acetabulum will be completely normalized by nonoperative treatment methods, which may include Pavlik and brace treatment as well as formal closed reduction and hip spica casting. In many cases, this ideal result cannot be achieved and the child is left with residual dysplasia, which is often not symptomatic. Other patients may present late with hip dysplasia that is not identified in early childhood. Some develop hip pain with no prior known hip problem. Other children have asymptomatic dysplasia that is picked up on an incidental radiograph. The orthopaedic literature is clear regarding the need for corrective hip osteotomies in symptomatic children. Surgery to correct asymptomatic hip dysplasia remains controversial. Children who have no symptoms yet have abnormal radiographs present a puzzling circumstance. In these cases, surgeons need to use quoted radiographic normal values for acetabular coverage of the femoral head as well as long-term natural history studies to decide whether to proceed with a corrective acetabular osteotomy. Long-term follow-up studies confirm that even patients with borderline dysplasia are likely to have significant hip symptoms and arthritis by middle age. Many children and adolescents with asymptomatic residual hip dysplasia should have corrective acetabular procedures performed. Surgery is more easily performed with more predictable results when the child is younger than 8 years. It is impossible to state with certainty which children with residual radiographic hip dysplasia, but without symptoms, should have a corrective acetabular osteotomy. Review of the literature confirms that many patients have been undertreated in the past, with a high percentage of children with borderline hip dysplasia developing premature arthritis in early to mid-adult life. Current data suggest that surgery should be performed in borderline cases. Skill of the surgeon in performing acetabular osteotomies and/or ease of referral to a treatment center may temper the timing of such decisions.

Giant dermatofibroma - a rare clinical variant

Dermatofibroma , also known as benign fibrous histiocytoma is a soft tissue tumor that usually occur in the mid adult life and shows a slight female predominance. Giant dermatofibroma , a very rare clinical variant is characterised by its unusually large size , benign biological behaviour despite its large size and same histopathological characterstics as conventional dermatofibroma .. We report a case of a 20 years old female presenting with a rapidly enlarging large mass in right leg in calf muscle region with history of progressive enlargement for past 4 years. The mass measured 13cm in greatest dimension. The patient underwent total excision of the tumor with wide local margin and histopathological examination confirmed it to be Giant dermatofibroma. Microscopic picture showed fibroblastic proliferation with collagen production , histiocytes and storiform pattern and focal lymphocytic infiltrates. Regular follow up showed no recurrence .This case is reported due to its very rare occurance , academic interest and to differentiate giant dermatofibroma from other such conditions such as desmoid tumor and dermofibrosarcoma protubens .

Childhood psychosocial adversity and adult cortisol patterns.

Cortisol levels may be altered in childhood in association with maltreatment (neglect, abuse and witnessing abuse) and other adversities, yet little is known about whether effects on cortisol persist into later life. To establish whether childhood psychosocial adversities predict cortisol levels in mid-adulthood. Childhood psychosocial adversities were ascertained in the 1958 British birth cohort and cortisol was measured in two saliva samples, one 45 min after awaking (T(1)) and the other 3 h later the same day (T(2)), from 6524 participants aged 45 years. No association was seen for abuse or household dysfunction in childhood and adult cortisol levels. In women but not men, T(1) cortisol was lowered by 7.9% per unit increase in childhood neglect score (range 0-3); T(1) to T(2) cortisol decline was less steep. High levels of maltreatment (abuse, neglect, witnessed abuse) were associated with >25% lower T(1) cortisol in both men and women, and 24% higher T(2) cortisol for men after adjustment for concurrent depressive/anxiety symptoms. In a non-clinical population, cumulative maltreatments in childhood were associated with flattened morning cortisol secretion in mid-adult life.

An Uncommon Malignancy of the Breast; Dermatofibrosarcoma Protruberans- A Case Report

Dermatofibrosarcoma protruberans(DFSP) is rare, morphologically distinct dermal/ subcutaneous neoplasm [1]. It typically presents during early or mid adult life. It is most common in the trunk and extremities and it accounts for approximately 0.1 % of all cutaneous malignancies and 6 % of all soft tissue sarcomas [2–4]. DFSP is highly aggressive, invades locally and rarely metastasizes [4]. Surgical scars, old burns, contractures and sites of vaccinations have all been reported as DFSP sites [5, 6]. DFSP occurring in the breast is very unusual. A review of literature reveals very few cases of DFSP breast. DFSP in the breast is usually characterized by smooth mobile raised reddish mass with brownish plaque like cutaneous thickening [6]. Treatment is primarily surgical, with chemotherapy and radiation therapy sometimes being used [6, 7].

Incident Gout in Women and Association with Obesity in the Atherosclerosis Risk in Communities (ARIC) Study

BackgroundWe hypothesized that women with early- and mid-adult life obesity, as well as high mid-adult life waist-to-hip ratios, and high weight gain during adulthood, experience a greater incidence of gout. MethodsWe examined the incidence of gout in the Atherosclerosis Risk in Communities Study, a population-based biracial cohort comprised of individuals aged 45-65 years at baseline (1987-1989). A total of 6263 women without prior history of gout were identified. We examined the association of body mass index (BMI) and obesity at cohort entry and at age 25 years, waist-to-hip ratio, and weight change with gout incidence (1996-1998). ResultsOver 9 years of follow-up, 106 women developed gout. The cumulative incidence of gout, by age 70 years, according to BMI category at baseline of <25, 25-29.9, 30-34.9, and ≥35 kg/m2, was 1.9, 3.6, 7.9, and 11.8%, respectively (P <.001). Obese women (BMI ≥30) at baseline had an adjusted 2.4-fold greater risk of developing gout than nonobese women (95% confidence interval [CI], 1.53-3.68). This association was attenuated after further adjustment for urate levels. Further, early adult obesity in women was associated with a 2.8-fold increased risk of gout compared with nonobese women (95% CI, 1.33-6.09), which remained statistically significant after baseline urate adjustment. There was a graded association between each anthropometric measure, including weight gain, with incident gout (each P for trend <.001). The results were similar in black and white women. ConclusionsIn a large cohort of black and white women, obesity in early- and mid-adulthood, and weight gain during this interval, were each independent risk factors for incident gout in women.

Neuroferritinopathy: a new inborn error of iron metabolism

Neuroferritinopathy is an autosomal dominant progressive movement disorder which occurs due to mutations in the ferritin light chain gene (FTL1). It presents in mid-adult life and is the only autosomal dominant disease in a group of conditions termed neurodegeneration with brain iron accumulation (NBIA). We performed brain MRI scans on 12 asymptomatic descendants of known mutation carriers. All three harbouring the pathogenic c.460InsA mutation showed iron deposition; these findings show pathological iron accumulation begins in early childhood which is of major importance in understanding and developing treatment for NBIA.