Psychological risk factors for chronic post-surgical pain after inguinal hernia repair surgery:a prospective cohort study.

A significant proportion of patients experience chronic post-surgical pain (CPSP) following inguinal hernia surgery. Psychological models are useful in predicting acute pain after surgery, and in predicting the transition from acute to chronic pain in non-surgical contexts. This is a prospective cohort study to investigate psychological (cognitive and emotional) risk factors for CPSP after inguinal hernia surgery. Participants were asked to complete questionnaires before surgery and 1 week and 4 months after surgery. Data collected before surgery and 1 week after surgery were used to predict pain at 4 months. Psychological risk factors assessed included anxiety, depression, fear-avoidance, activity avoidance, catastrophizing, worry about the operation, activity expectations, perceived pain control and optimism. The study included 135 participants; follow-up questionnaires were returned by 119 (88.1%) and 115 (85.2%) participants at 1 week and 4 months after surgery respectively. The incidence of CPSP (pain at 4 months) was 39.5%. After controlling for age, body mass index and surgical variables (e.g. anaesthetic, type of surgery and mesh type used), lower pre-operative optimism was an independent risk factor for CPSP at 4 months; lower pre-operative optimism and lower perceived control over pain at 1 week after surgery predicted higher pain intensity at 4 months. No emotional variables were independently predictive of CPSP. Further research should target these cognitive variables in pre-operative psychological preparation for surgery. © 2011 European Federation of International Association for the Study of Pain Chapters.

Verteporfin photodynamic therapy cohort study:report 1: effectiveness and factors influencing outcomes

Purpose - To compare the visual outcomes after verteporfin photodynamic therapy (VPDT) administered in routine clinical practice with those observed in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) trials and to quantify the effects of clinically important baseline covariates on outcome. Design - A prospective longitudinal study of patients treated with VPDT in 45 ophthalmology departments in the United Kingdom with expertise in the management of neovascular age-related macular degeneration (nAMD). Participants - Patients with wholly or predominantly classic choroidal neovascularization (CNV) of any cause with a visual acuity =20/200 in the eye to be treated. Methods - Refracted best-corrected visual acuity (BCVA) and contrast sensitivity were measured in VPDT-treated eyes at baseline and subsequent visits. Eyes were retreated at 3 months if CNV was judged to be active. Baseline angiograms were graded to quantify the percentages of classic and occult CNV. Treated eyes were categorized as eligible or ineligible for TAP, or unclassifiable. Main Outcome Measures - Best-corrected visual acuity and contrast sensitivity during 1 year of follow-up after initial treatment. Results - A total of 7748 treated patients were recruited. Data from 4043 patients with a diagnosis of nAMD were used in the present analysis. Reading center determination of lesion type showed that 87% were predominantly classic CNV. Eyes received 2.4 treatments in year 1 and 0.4 treatments in year 2. Deterioration of BCVA over 1 year was similar to that observed in the VPDT arms of the TAP trials and was not influenced by TAP eligibility classification. Best-corrected visual acuity deteriorated more quickly in current smokers; with increasing proportion of classic CNV, increasing age, and better baseline BCVA; and when the fellow eye was the better eye.

Examining factors associated with excess mortality in older people (age ≥ 70 years) with diabetes - a 10-year cohort study of older people with and without diabetes

Aims: To compare all-cause mortality in older people with or without diabetes and consider the associated risk of comorbidity and polypharmacy. Methods: A 10-year cohort study using data from the Health Innovation Network database (2003-2013) comparing mortality in people aged ≥ 70 years with diabetes (DM cohort) (n = 35 717) and without diabetes (No DM cohort) (n = 307 918). Results: The mean age of the DM cohort was 78.1 ± 5.8 years vs. 79.0 ± 6.3 years in the No DM cohort. Mean diabetes duration was 8.2 ± 8.1 years, and 30% had diabetes for > 10 years. The DM cohort had a greater comorbidity load and people in this cohort were prescribed more therapies than the No DM cohort. The 5- and 10-year survival rates were lower in the DM cohort at 64% and 39%, respectively, compared with 72% and 50% in the No DM cohort. The excess mortality in the DM cohort was greatest in those aged <75 years with longer duration diabetes, the relative hazard for mortality was higher in females. Although comorbidity and polypharmacy were associated with increased mortality risk in the DM cohort, this risk was lower compared with the No DM cohort. The hazard ratios (95% confidence interval) for comorbidities > 4 and medicines ≥ 7 were 1.29 (1.19 to 1.41) and 1.34 (1.25 to 1.43) in the DM cohort and 1.63 (1.57 to 1.70) and 1.48 (1.40 to 1.56) in the No DM cohort, respectively. Conclusions: There is significant excess mortality in older people with diabetes, which is unexplained by comorbidity or polypharmacy. This excess is greatest in the younger old with longer disease duration, suggesting that it may be related to the effect of diabetes exposure.

The impact of bariatric surgery on estimated glomerular filtration rate in patients with type 2 diabetes:a retrospective cohort study

Background: Diabetes mellitus is the most common cause of end-stage renal disease, which is associated with increased morbidity and mortality. The impact of bariatric surgery on chronic kidney disease is unclear. Objectives: Our primary aim was to assess the impact of bariatric surgery on estimated glomerular filtration rate (eGFR) in type 2 diabetes (T2D) patients. Our secondary aim was to compare the impact of bariatric surgery versus routine care on eGFR in patients with T2D. Setting: University Hospital, United Kingdom. Methods: A retrospective cohort analysis of adults with T2D who underwent bariatric surgery at a single center between January 2005 and December 2012. Data regarding eGFR were obtained from electronic patients records. eGFR was calculated using the Modification of Diet in Renal Disease formula. Data regarding patients with T2D who did not undergo bariatric surgery ("routine care") were obtained from patients attending the diabetes clinic at the same center from 2009 to 2011. Results: One hundred sixty-three patients were included (mean age 48.5±8.8 yr; baseline body mass index 50.8±9.1 kg/m2) and were followed for 3.0±2.3 years. Bariatric surgery resulted in an improvement in eGFR (median [interquartile range] 86.0 [73.0-100.0] versus 92.0 [77.0-101.0] mL/min/1.73 m2 for baseline versus follow-up, respectively; P = .003), particularly in patients with baseline eGFR≤60 mL/min/1.73 m2 (48.0 [42.0-57.0] versus 61.0 [55.0-63.0] mL/min/1.73 m2; P = .004). After adjusting for baseline eGFR, glycated hemoglobin (HbA1C), body mass index, age, and gender, bariatric surgery was associated with higher study-end eGFR compared with routine care (B = 7.787; P< .001). Conclusion: Bariatric surgery results in significant improvements in eGFR in T2D patients, particularly those with an eGFR≤60 mL/min/1.73 m2, while routine care was associated with a decline in eGFR.

Balance ability in 7- and 10-year-old children:associations with prenatal lead and cadmium exposure and with blood lead levels in childhood in a prospective birth cohort study

OBJECTIVES: Most studies reporting evidence of adverse effects of lead and cadmium on the ability to balance have been conducted in high-exposure groups or have included adults. The effects of prenatal exposure have not been well studied, nor have the effects in children been directly studied. The aim of the study was to identify the associations of lead (in utero and in childhood) and cadmium (in utero) exposure with the ability to balance in children aged 7 and 10 years. DESIGN: Prospective birth cohort study. PARTICIPANTS: Maternal blood lead (n=4285) and cadmium (n=4286) levels were measured by inductively coupled plasma mass spectrometry in women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) during pregnancy. Child lead levels were measured in a subsample of 582 of ALSPAC children at age 30 months. MAIN OUTCOME MEASURES: Children completed a heel-to-toe walking test at 7 years. At 10 years, the children underwent clinical tests of static and dynamic balance. Statistical analysis using SPSS V.19 included logistic regression modelling, comparing categories of ≥ 5 vs <5 µg/dL for lead, and ≥ 1 vs <1 µg/L for cadmium. RESULTS: Balance at age 7 years was not associated with elevated in utero lead or cadmium exposure (adjusted OR for balance dysfunction: Pb 1.01 (95% CI 0.95 to 1.01), n=1732; Cd 0.95 (0.77 to 1.20), n=1734), or with elevated child blood lead level at age 30 months (adjusted OR 0.98 (0.92 to 1.05), n=354). Similarly, neither measures of static nor dynamic balance at age 10 years were associated with in utero lead or cadmium exposure, or child lead level. CONCLUSIONS: These findings do not provide any evidence of an association of prenatal exposure to lead or cadmium, or lead levels in childhood, on balance ability in children. Confirmation in other cohorts is needed.

Prenatal alcohol exposure and childhood balance ability:findings from a UK birth cohort study

OBJECTIVE: To investigate the association of prenatal alcohol exposure with balance in10-year-old children. DESIGN: Population-based prospective longitudinal study. SETTING: Former Avon region of UK (Southwest England). PARTICIPANTS: 6915 children from the Avon Longitudinal Study of Parents and Children who had a balance assessment at age 10 and had data on maternal alcohol consumption. OUTCOME MEASURES: 3 composite balance scores: dynamic balance (beam-walking), static balance eyes open, static balance eyes closed (heel-to-toe balance on a beam and standing on one leg, eyes open or closed). RESULTS: Most mothers (95.5%) consumed no-to-moderate amounts (3-7 glasses/week) of alcohol during pregnancy. Higher total-alcohol consumption was associated with maternal-social advantage, whereas binge drinking (≥4 units/day) and abstinence were associated with maternal social disadvantage. No evidence was found of an adverse effect of maternal-alcohol consumption on childhood balance. Higher maternal-alcohol use during pregnancy was generally associated with better offspring outcomes, with some specific effects appearing strong (static balance eyes open and moderate total alcohol exposure at 18 weeks, adjusted OR 1.23 (95% CI 1.01 to 1.49); static balance eyes closed and moderate total alcohol exposure at 18 weeks, adjusted OR 1.25 (95% CI 1.06 to 1.48). Similar results were found for both paternal and postnatal maternal alcohol exposure. A Mendelian-randomization approach was used to estimate the association between maternal genotype and offspring balance using the non-synonymous variant rs1229984*A (ADH1B) to proxy for lower maternal alcohol consumption; no strong associations were found between this genotype/proxy and offspring balance. CONCLUSIONS: No evidence was found to indicate that moderate maternal alcohol consumption in this population sample had an adverse effect on offspring balance at age 10. An apparent beneficial effect of higher total maternal alcohol consumption on offspring balance appeared likely to reflect residual confounding.

Prevalence and risk factors for mild and high-frequency bilateral sensorineural hearing loss at age 11 years old:a UK prospective cohort study

OBJECTIVE: This study aimed to assess prevalence and risk factors for mild/high-frequency bilateral sensorineural hearing loss within a UK population of children at age 11 years. DESIGN: Prospective birth cohort study. STUDY SAMPLE: Repeat hearing thresholds were measured in 5032 children, as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 7, 9, and 11 years. Pregnancy, birth, and early medical history were obtained prospectively through parental questionnaires and medical records. RESULTS: Twenty children had mild and seven had high-frequency bilateral sensorineural hearing loss, giving a combined prevalence of 0.5% (95% CI 0.4-0.8%). These children were more likely than the rest of the study sample to have been admitted to hospital at 6-18 months (OR 2.7, 95% CI 1.00-7.30). Parents of these children were more likely to have suspected a hearing problem when the children were 3 years old (OR 2.4, 95% CI 1.05-5.60). CONCLUSIONS: This is the first UK prospective cohort study to investigate the prevalence of mild and high-frequency hearing loss. This study, which has the advantage of a large sample size and repeat hearing measures over a four year period, reports lower prevalence values than US cross-sectional studies.

The prevalence of tympanic membrane and related middle ear pathology in children:a large longitudinal cohort study followed from birth to age ten

OBJECTIVE: To record with video-otoscopy the appearance of the tympanic membranes of a cross section of children aged 9 to 10 years. STUDY DESIGN: Cross-sectional study nested within an established longitudinal study of childhood development, the Avon Longitudinal Study of Parents and Children. SETTING: South West England, U.K. PARTICIPANTS: Approximately 6908 of 7261 children with ages ranging from 105 to 140 months born between April 1, 1991, and December 31, 1992, were examined by trained technicians with video-otoscopy. MAIN OUTCOME MEASURES: Two photographs were taken of each child's tympanic membranes to show the features of the pars tensa and the pars flaccida. RESULTS: In just less than three quarters of the children, both ears were normal. Retraction of the pars flaccida was present in 9.6% of children, and that of the pars tensa was present in 7.9%. Most of these changes were mild with few severe retractions. There were 15 cases of overt or suspected cholesteatoma. CONCLUSION: The tympanic membrane changes reflect most of the middle ear disease seen in 9- to 10-year-old children. The prevalence is low, and few children have serious disease at this stage.

Balance ability of 7 and 10 year old children in the population:results from a large UK birth cohort study

OBJECTIVE: The literature contains many reports of balance function in children, but these are often on atypical samples taken from hospital-based clinics and may not be generalisable to the population as a whole. The purpose of the present study is to describe balance test results from a large UK-based birth cohort study. METHODS: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were analysed. A total of 5402 children completed the heel-to-toe walking test at age 7 years. At age 10 years, 6915 children underwent clinical tests of balance including beam-walking, standing heel-to-toe on a beam and standing on one leg. A proportion of the children returned to the clinic for retesting within 3 months allowing test-retest agreement to be measured. RESULTS: Frequency distributions for each of the balance tests are given. Correlations between measures of dynamic balance at ages 7 and 10 years were weak. The static balance of 10 year old children was found to be poorer with eyes closed than with eyes open, and poorer in boys than in girls for all measures. Balance on one leg was poorer than heel-to-toe balance on a beam. A significant learning effect was found when first and second attempts of the tests were compared. Measures of static and dynamic balance appeared independent. Consistent with previous reports in the literature, test-retest reliability was found to be low. CONCLUSIONS: This study provides information about the balance ability of children aged 7 and 10 years and provides clinicians with reference data for balance tests commonly used in the paediatric clinic.

The impact of anticholinergic burden in Alzheimer's dementia-the LASER-AD study

Objective - to examine the effect of medications with anticholinergic effects on cognitive impairment and deterioration in Alzheimer's dementia (AD). Methods - cognitive function was measured at baseline and at 6- and 18-month follow-up using the Mini-Mental State Exam (MMSE), the Severe Impairment Battery (SIB) and the Alzheimer's Disease Assessment Battery, Cognitive subsection (ADAS-COG) in a cohort study of 224 participants with AD. Baseline anticholinergic Burden score (ABS) was measured using the Anticholinergic Burden scale and included all prescribed and over the counter medication. Results - the sample was 224 patients with Alzheimer's dementia and 71.4% were women. Their mean age was 81.0 years [SD 7.4 (range 55–98)]. The mean number of medications taken was 3.6 (SD 2.4) and the mean anticholinergic load was 1.1 (SD 1.4, range 0–7). The total number of drugs taken and anticholinergic load correlated (rho = 0.44; P < 0.01). There were no differences in MMSE and other cognitive functioning at either 6 or 18 months after adjusting for baseline cognitive function, age, gender and use of cholinesterase inhibitors between those with, and those without high anticholinergenic load. Conclusions - medications with anticholinergic effect in patients with AD were not found to effect deterioration in cognition over the subsequent 18 months. Our study did not support a continuing effect of these medications on people with AD who are established on them.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema:a prospective, multicentre, UK study

Objectives: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. Design: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. Setting: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Participants: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Interventions: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. Main outcome measures: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Results: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Conclusions: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. © Queen's Printer and Controller of HMSO 2013.

Prevalence and audiological features in carriers of GJB2 mutations, c.35delG and c.101T>C (p.M34T), in a UK population study

OBJECTIVES: To determine the carrier rate of the GJB2 mutation c.35delG and c.101T>C in a UK population study; to determine whether carriers of the mutation had worse hearing or otoacoustic emissions compared to non-carriers. DESIGN: Prospective cohort study. SETTING: University of Bristol, UK. PARTICIPANTS: Children in the Avon Longitudinal Study of Parents and Children. 9202 were successfully genotyped for the c.35delG mutation and c.101>T and classified as either carriers or non-carriers. OUTCOME MEASURES: Hearing thresholds at age 7, 9 and 11 years and otoacoustic emissions at age 9 and 11. RESULTS: The carrier frequency of the c.35delG mutation was 1.36% (95% CI 1.13 to 1.62) and c.101T>C was 2.69% (95% CI 2.37 to 3.05). Carriers of c.35delG and c.101T>C had worse hearing than non-carriers at the extra-high frequency of 16 kHz. The mean difference in hearing at age 7 for the c.35delG mutation was 8.53 dB (95% CI 2.99, 14.07) and 12.57 dB at age 9 (95% CI 8.10, 17.04). The mean difference for c.101T>C at age 7 was 3.25 dB (95% CI -0.25 to 6.75) and 7.61 dB (95% CI 4.26 to 10.96) at age 9. Otoacoustic emissions were smaller in the c.35delG mutation carrier group: at 4 kHz the mean difference was -4.95 dB (95% CI -6.70 to -3.21) at age 9 and -3.94 dB (95% CI -5.78 to -2.10) at age 11. There was weak evidence for differences in otoacoustic emissions amplitude for c.101T>C carriers. CONCLUSION: Carriers of the c.35delG mutation and c.101T>C have worse extra-high-frequency hearing than non-carriers. This may be a predictor for changes in lower-frequency hearing in adulthood. The milder effects observed in carriers of c.101T>C are in keeping with its classification as a mutation causing mild/moderate hearing loss in homozygosity or compound heterozygosity.