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Whole apples are a source of pectin and polyphenols, both of which show potential to modulate postprandial lipaemia (PPL). The present study aimed to explore the effects of whole apple consumption on PPL, as a risk factor for CVD, in generally healthy but overweight and obese adults. A randomised, crossover acute meal trial was conducted with seventeen women and nine men (mean BMI of 34·1 (sem 0·2) kg/m2). Blood samples were collected for 6 h after participants consumed an oral fat tolerance test meal that provided 1 g fat/kg body weight and 1500 mg acetaminophen per meal for estimating gastric emptying, with and without three whole raw Gala apples (approximately 200 g). Plasma TAG (with peak postprandial concentration as the primary outcome), apoB48, chylomicron-rich fraction particle size and fatty acid composition, glucose, insulin and acetaminophen were analysed. Differences between with and without apples were identified by ANCOVA. Apple consumption did not alter postprandial TAG response, chylomicron properties, glucose or acetaminophen (P > 0·05), but did lead to a higher apoB48 peak concentration and exaggerated insulin between 20 and 180 min (P < 0·05). Overall, as a complex food matrix, apples did not modulate postprandial TAG when consumed with a high-fat meal in overweight and obese adults, but did stimulate insulin secretion, potentially contributing to an increased TAG-rich lipoprotein production.
Most research on the causes of women's underrepresentation examines one of two stages of the political pipeline: the development of nascent political ambition or specific aspects of the campaign and election process. In this article, we make a different kind of contribution. We build on the growing literature on gender, psychology, and representation to provide an analysis of what kinds of men and women make it through the political pipeline at each stage. This allows us to draw some conclusions about the ways in which the overall process is similar and different for women and men. Using surveys of the general U.S. population (N = 1,939) and elected municipal officials such as mayors and city councilors (N = 2,354) that measure the distribution of Big Five personality traits, we find that roughly the same types of men and women have nascent political ambition; there is just an intercept shift for sex. In contrast, male and female elected officials have different personality profiles. These differences do not reflect underlying distributions in the general population or the population of political aspirants. In short, our data suggest that socialization into political ambition is similar for men and women, but campaign and election processes are not.
Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.
To describe snacking characteristics and patterns in children and examine associations with diet quality and BMI.
Children’s weight and height were measured. Participants/adult proxies completed multiple 24 h dietary recalls. Snack occasions were self-identified. Snack patterns were derived for each sample using exploratory factor analysis. Associations of snacking characteristics and patterns with Healthy Eating Index-2010 (HEI-2010) score and BMI were examined using multivariable linear regression models.
Childhood Obesity Prevention and Treatment Research (COPTR) Consortium, USA: NET-Works, GROW, GOALS and IMPACT studies.
Two snack patterns were derived for three studies: a meal-like pattern and a beverage pattern. The IMPACT study had a similar meal-like pattern and a dairy/grains pattern. A positive association was observed between meal-like pattern adherence and HEI-2010 score (P for trend < 0⋅01) and snack occasion frequency and HEI-2010 score (β coefficient (95 % CI): NET-Works, 0⋅14 (0⋅04, 0⋅23); GROW, 0⋅12 (0⋅02, 0⋅21)) among younger children. A preference for snacking while using a screen was inversely associated with HEI-2010 score in all studies except IMPACT (β coefficient (95 % CI): NET-Works, −3⋅15 (−5⋅37, −0⋅92); GROW, −2⋅44 (−4⋅27, −0⋅61); GOALS, −5⋅80 (−8⋅74, −2⋅86)). Associations with BMI were almost all null.
Meal-like and beverage patterns described most children’s snack intake, although patterns for non-Hispanic Blacks or adolescents may differ. Diets of 2–5-year-olds may benefit from frequent meal-like pattern snack consumption and diets of all children may benefit from decreasing screen use during eating occasions.
Working memory (WM) deficits are seen as a core deficit in schizophrenia, implicated in the broad cognitive impairment seen in the illness. Here we examine the impact of WM storage of a single item on the operation of other cognitive systems.
We studied 37 healthy controls (HCS) and 43 people with schizophrenia (PSZ). Each trial consisted of a sequence of two potential target stimuli, T1 and T2. T1 was a letter presented for 100 ms. After delays of 100–800 ms, T2 was presented. T2 was a 1 or a 2 and required a speeded response. In one condition, subjects were instructed to ignore T1 but respond to T2. In another condition, they were required to report T1 after making their speeded response to T2 (i.e. to make a speeded T2 response while holding T1 in WM).
PSZ were dramatically slowed at responding to T2 when T1 was held in WM. A repeated measures ANOVA yielded main effects of group, delay, and condition with a group by condition interaction (p's < 0.001). Across delays, the slowing of the T2 response when required to hold T1 in memory, relative to ignoring T1, was nearly 3 times higher in PSZ than HCS (633 v. 219 ms).
Whereas previous studies have focused on reduced storage capacity, the present study found that PSZ are impaired at performing tasks while they are successfully maintaining a single item in WM. This may play a role in the broad cognitive impairment seen in PSZ.
Introduction: Emergency department (ED) staff carry a high risk for the burnout syndrome of increased emotional exhaustion, depersonalization and decreased personal accomplishment. Previous research has shown that task-oriented coping skills were associated with reduced levels of burnout compared to emotion-oriented coping. ED staff at one hospital participated in an intervention to teach task-oriented coping skills. We hypothesized that the intervention would alter staff coping behaviors and ultimately reduce burnout. Methods: ED physicians, nurses and support staff at two regional hospitals were surveyed using the Maslach Burnout Inventory (MBI) and the Coping Inventory for Stressful Situations (CISS). Surveys were performed before and after the implementation of communication and conflict resolution skills training at the intervention facility (I) consisting of a one-day course and a small group refresher 6 to 15 months later. Descriptive statistics and multivariate analysis assessed differences in staff burnout and coping styles compared to the control facility (C) and over time. Results: 85/143 (I) and 42/110 (C) ED staff responded to the initial survey. Post intervention 46 (I) and 23(C) responded. During the two year study period there was no statistically significant difference in CISS or MBI scores between hospitals (CISS: (Pillai's trace = .02, F(3,63) = .47, p = .71, partial η2 = .02); MBI: (Pillai's trace = .01, F(3,63) = .11, p = .95, partial η2 = .01)) or between pre- and post-intervention groups (CISS: (Pillai's trace = .01, F(3,63) = .22, p = .88, partial η2 = .01); MBI: (Pillai's trace = .09, F(3,63) = 2.15, p = .10, partial η2 = .01)). Conclusion: We were not able to measure improvement in staff coping or burnout in ED staff receiving communication skills intervention over a two year period. Burnout is a multifactorial problem and environmental rather than individual factors may be more important to address. Alternatively, to demonstrate a measurable effect on burnout may require more robust or inclusive interventions.
Introduction: In Nova Scotia, under the Paramedics Providing Palliative Care program, paramedics can now manage symptom crises in patients with palliative care goals and often at home without the need to transport to hospital. Growing recognition that non-cancer conditions benefit from a palliative approach is expanding the program. Our team previously found treatment of pain and breathlessness is not optimized, pain scores are underutilized, and paramedics were more comfortable (pre-launch) with a palliative approach in cancer versus non-cancer conditions. Our objective was to compare symptom management in cancer versus non-cancer subgroup. Methods: We conducted a retrospective cohort study. The Electronic Patient Care Record and Special Patient Program were queried for patients with palliative goals from July 1, 2015 to July 1, 2016. Descriptive analysis was conducted and results were compared with a t-test and Bonferroni correction (alpha = p < 0.007). Results: 1909 unique patients; 765/1909 (40.1%) cancer and 1144/1909 (59.9%) non-cancer. Female sex: cancer 357/765 (46.7%), non-cancer 538/1144 (47.0%). Mean age cancer: 73.3 (11.65), non-cancer 77.7 (12.80). Top non-cancer conditions: COPD (495/1144, 43.3%), CHF (322/1144, 28.1%), stroke (172/1144, 15.0%) and dementia (149/1144, 13.0%). Comorbidities for cancer patients (range): 0 to 3; non-cancer 0 to 5. Most common chief complaint (CC) for cancer and non-cancer: respiratory distress, 10.8% vs 21.5%. Overall, no difference in proportion treated cancer vs non-cancer, 11.5% vs 10.1%, p = 0.35. Some difference in individual therapies: morphine 83/765 (10.8%) vs 55/1144 (4.8%), p < 0.001, hydromorphone 9/765 (1.2%) vs 2/1144 (0.2%), p = 0.014, salbutamol 38/765 (5.0%) vs 5/1144 (0.4%), p < 0.001 and ipratropium 27/765 (3.5%) vs 134/1144 (11.7%), p < 0.001, in addition to any support with home medication which is not queriable. Pre-treatment pain scores were documented more often than post-treatment in both groups (58.7% vs 25.6% (p < 0.001), 57.4% vs 26.9% (p < 0.001)). Conclusion: Non-cancer patients represent an important proportion of palliative care calls for paramedics. Cancer and non-cancer patients had very similar CC and received similar treatment, although low proportions, despite pre-launch findings that non-cancer conditions were likely to be undertreated. Pain scores remain underutilized. Further research into the underlying reason(s) is required to improve the support of non-cancer patients by paramedics.
Since 2008 England's anti-stigma programme Time to Change has lobbied media outlets about stigmatising coverage and worked with them to promote accurate and non-stigmatising coverage. While this may have an impact on coverage and hence attitudes, it is also possible that coverage can change in response to improving attitudes, through the creation of a market demand for less stigmatising coverage. This study evaluates English newspaper coverage of mental health topics between 2008 and 2016.
Articles covering mental health in 27 newspapers were retrieved using keyword searches on two randomly chosen days each month in 2008–2016, excluding 2012 and 2015 due to restricted resources. Content analysis used a structured coding framework. Univariate logistic regression models were used to estimate the odds of each hypothesised element occurring in 2016 compared with 2008 and Wald tests to assess the overall statistical significance of the year variable as the predictor.
The sample retrieved almost doubled between 2008 (n = 882) and 2016 (n = 1738). We found a significant increase in the proportion of anti-stigmatising articles (odds ratio (OR) 2.26 (95% confidence interval (CI) 1.86–2.74)) and a significant decrease in stigmatising articles (OR 0.62 (95% CI 0.51–0.75)). Reports on all diagnoses except for schizophrenia were more often anti-stigmatising than stigmatising.
This is the first clear evidence of improvement in coverage since the start of Time to Change. However, coverage of schizophrenia may be less affected by this positive shift than that of other diagnoses. The increase in the level of coverage identified in 2016 requires further investigation, as it may also influence public conceptualisation of what constitutes mental illness, attitudes to mental illness in general and/or specific diagnoses. While most anti-stigma programmes are not diagnosis specific, we suggest their evaluation would benefit from a diagnosis specific approach to allow fuller interpretation of their effects. This could include media analysis driven by hypotheses based on diagnoses to ascertain whether variations by diagnosis over time occur both in the nature and in the proportion of coverage.
There is an increasing incidence of overweight/obesity and mental health disorders in young adults and the two conditions often coexist. We aimed to investigate the influence of antenatal and postnatal factors that may underlie this association with a focus on maternal prenatal smoking, socio-economic status and gender. Data from the Western Australian Pregnancy Cohort (Raine) Study (women enrolled 1989–1991) including 1056 offspring aged 20 years (cohort recalled 2010–2012) were analyzed (2015–2016) using multivariable models for associations between offspring depression scores (DASS-21 Depression-scale) and body mass index (BMI), adjusting for pregnancy and early life factors and offspring behaviours. There was a significant positive relationship between offspring depression-score and BMI independent of gender and other psychosocial covariates. There was a significant interaction between maternal prenatal smoking and depression-score (interaction coefficient=0.096; 95% CI: 0.006, 0.19, P=0.037), indicating the relationship between depression-score and BMI differed according to maternal prenatal smoking status. In offspring of maternal prenatal smokers, a positive association between BMI and depression-score (coefficient=0.133; 95% CI: 0.05, 0.21, P=0.001) equated to 1.1 kg/m2 increase in BMI for every 1standard deviation (8 units) increase in depression-score. Substituting low family income during pregnancy for maternal prenatal smoking in the interaction (interaction coefficient=0.091; 95% CI: 0.01, 0.17, P=0.027) showed a positive association between BMI and depression score only among offspring of mothers with a low family income during pregnancy (coefficient=0.118; 95% CI: 0.06, 0.18, P<0.001). There were no significant effects of gender on these associations. Whilst further studies are needed to determine whether these associations are supported in other populations, they suggest potentially important maternal behavioural and socio-economic factors that identify individuals vulnerable to the coexistence of obesity and depression in early adulthood.
Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases. These investigations increased the total number of cases to seven. All confirmed cases shared a very similar WGS profile. Two more cases were epidemiologically linked, but no laboratory confirmation exists. Despite all the efforts done, the source of the outbreak was not identified, but the transmission was controlled. The investigation was conducted by a team including epidemiologists and microbiologists from five countries (Finland, Israel, Romania, Sweden and the UK) and from the European Centre for Disease Prevention and Control. Our report shows how countries can collaborate to control the spread of XDR TB by exchanging information about cases and their contacts to enable identification of additional cases and transmission and to perform the source investigation.
Despite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.
Materials and methods
The modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation.
Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting.
Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.
Many novel therapeutic options for depression exist that are either not mentioned in clinical guidelines or recommended only for use in highly specialist services. The challenge faced by clinicians is when it might be appropriate to consider such ‘non-standard’ interventions. This analysis proposes a framework to aid this decision.
Declaration of interest
In the past 3 years R.H.M.W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, LivaNova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. D.M.B.C. has received fees from LivaNova for attending an advisory board. In the past 3 years A.J.C. has received fees for lecturing from Astra Zeneca and Lundbeck; fees for consulting from LivaNova, Janssen and Allergan; and research grant support from Lundbeck.
In the past 3 years A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. In the past 3 years A.L.M. has received support for attending seminars and fees for consultancy work (including advisory board) from Medtronic Inc and LivaNova. R.M. holds joint research grants with a number of digital companies that investigate devices for depression including Alpha-stim, Big White Wall, P1vital, Intel, Johnson and Johnson and Lundbeck through his mindTech and CLAHRC EM roles. M.S. is an associate at Blueriver Consulting providing intelligence to NHS organisations, pharmaceutical and devices companies. He has received honoraria for presentations and advisory boards with Lundbeck, Eli Lilly, URGO, AstraZeneca, Phillips and Sanofi and holds shares in Johnson and Johnson. In the past 3 years P.R.A.S. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending an advisory board) from life sciences companies including Corcept Therapeutics, Indivior and LivaNova. In the past 3 years P.S.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has received funding for investigator initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth.
The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1·4), Asian (OR = 2·3), or Black (OR = 1·7), and more likely to live in an urban area (OR = 1·2), report international travel (OR = 1·5), and have infection in autumn or winter (OR = 1·2). Campylobacter upsaliensis patients were more likely female (OR = 1·6), Hispanic (OR = 1·6), have a blood isolate (OR = 2·8), and have an infection in autumn or winter (OR = 1·7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2·9) and have an infection in autumn or winter (OR = 1·7). Campylobacter fetus patients were more likely male (OR = 3·1), hospitalized (OR = 3·5), and have a blood isolate (OR = 44·1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12·5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.
Accurate and reproducible patient positioning is a critical step in radiotherapy for breast cancer. This has seen the use of permanent skin markings becoming standard practice in many centres. Permanent skin markings may have a negative impact on long-term cosmetic outcome, which may in turn, have psychological implications in terms of body image. The aim of this study was to investigate the feasibility of using a semi-permanent tattooing device for the administration of skin marks for breast radiotherapy set-up.
Materials and methods
This was designed as a phase II double-blinded randomised-controlled study comparing our standard permanent tattoos with the Precision Plus Micropigmentation (PPMS) device method. Patients referred for radical breast radiotherapy were eligible for the study. Each study participant had three marks applied using a randomised combination of the standard permanent and PPMS methods and was blinded to the type of each mark. Follow up was at routine appointments until 24 months post radiotherapy. Participants and a blind assessor were invited to score the visibility of each tattoo at each follow-up using a Visual Analogue Scale. Tattoo scores at each time point and change in tattoo scores at 24 months were analysed by a general linear model using the patient as a fixed effect and the type of tattoo (standard or research) as covariate. A simple questionnaire was used to assess radiographer feedback on using the PPMS.
In total, 60 patients were recruited to the study, of which 55 were available for follow-up at 24 months. Semi-permanent tattoos were more visible at 24 months than the permanent tattoos. Semi-permanent tattoos demonstrated a greater degree of fade than the permanent tattoos at 24 months (final time point) post completion of radiotherapy. This was not statistically significant, although it was more apparent for the patient scores (p=0·071) than the blind assessor scores (p=0·27). No semi-permanent tattoos required re-marking before the end of radiotherapy and no adverse skin reactions were observed.
The PPMS presents a safe and feasible alternative to our permanent tattooing method. An extended period of follow-up is required to fully assess the extent of semi-permanent tattoo fade.
The livestock sector is one of the fastest growing subsectors of the agricultural economy and, while it makes a major contribution to global food supply and economic development, it also consumes significant amounts of natural resources and alters the environment. In order to improve our understanding of the global environmental impact of livestock supply chains, the Food and Agriculture Organization of the United Nations has developed the Global Livestock Environmental Assessment Model (GLEAM). The purpose of this paper is to provide a review of GLEAM. Specifically, it explains the model architecture, methods and functionality, that is the types of analysis that the model can perform. The model focuses primarily on the quantification of greenhouse gases emissions arising from the production of the 11 main livestock commodities. The model inputs and outputs are managed and produced as raster data sets, with spatial resolution of 0.05 decimal degrees. The Global Livestock Environmental Assessment Model v1.0 consists of five distinct modules: (a) the Herd Module; (b) the Manure Module; (c) the Feed Module; (d) the System Module; (e) the Allocation Module. In terms of the modelling approach, GLEAM has several advantages. For example spatial information on livestock distributions and crops yields enables rations to be derived that reflect the local availability of feed resources in developing countries. The Global Livestock Environmental Assessment Model also contains a herd model that enables livestock statistics to be disaggregated and variation in livestock performance and management to be captured. Priorities for future development of GLEAM include: improving data quality and the methods used to perform emissions calculations; extending the scope of the model to include selected additional environmental impacts and to enable predictive modelling; and improving the utility of GLEAM output.
Resistance training (RT) and increased dietary protein are recommended to attenuate age-related muscle loss in the elderly. This study examined the effect of a lean red meat protein-enriched diet combined with progressive resistance training (RT+Meat) on health-related quality of life (HR-QoL) in elderly women. In this 4-month cluster randomised controlled trial, 100 women aged 60–90 years (mean 73 years) from self-care retirement villages participated in RT twice a week and were allocated either 160 g/d (cooked) lean red meat consumed across 2 meals/d, 6 d/week or ≥1 serving/d (25–30 g) carbohydrates (control group, CRT). HR-QoL (SF-36 Health Survey questionnaire), lower limb maximum muscle strength and lean tissue mass (LTM) (dual-energy X-ray absorptiometry) were assessed at baseline and 4 months. In all, ninety-one women (91 %) completed the study (RT+Meat (n 48); CRT (n 43)). Mean protein intake was greater in RT+Meat than CRT throughout the study (1·3 (sd 0·3) v. 1·1 (sd 0·3) g/kg per d, P<0·05). Exercise compliance (74 %) was not different between groups. After 4 months there was a significant net benefit in the RT+Meat compared with CRT group for overall HR-QoL and the physical component summary (PCS) score (P<0·01), but there were no changes in either group in the mental component summary (MCS) score. Changes in lower limb muscle strength, but not LTM, were positively associated with changes in overall HR-QoL (muscle strength, β: 2·2 (95 % CI 0·1, 4·3), P<0·05). In conclusion, a combination of RT and increased dietary protein led to greater net benefits in overall HR-QoL in elderly women compared with RT alone, which was because of greater improvements in PCS rather than MCS.
Eustachian tube dysfunction is a poorly defined condition associated with various symptoms and it can predispose to middle-ear disease. Balloon dilation Eustachian tuboplasty has been proposed as a treatment for Eustachian tube dysfunction.
To evaluate the subjective and objective outcomes of balloon dilation Eustachian tuboplasty in patients with recurrent, previously treated chronic Eustachian tube dysfunction.
The study was conducted on 11 patients (13 ears) who had undergone previous unsuccessful medical and surgical treatment. Tympanometry was the primary outcome measure. Secondary outcome measures included pure tone audiogram assessment and seven-item Eustachian Tube Dysfunction Questionnaire score.
Balloon dilation Eustachian tuboplasty resulted in significant improvements in 11 patients’ subjective but not objective outcome measures.
The objective abnormality and subjective symptoms in Eustachian tube dysfunction may represent two distinct pathological processes, which may nevertheless influence and exacerbate each other.