Defining Dry Eye from a Clinical Perspective

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.     

Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs) Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP) Analysis in Patients with Major Depressive Disorder

Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day), sertraline (n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041). Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.     

Indoor air quality and occupant satisfaction in five mechanically and four naturally ventilated open-plan office buildings

Occupant responses and indoor environment characteristics were recorded and compared in five mechanically and four naturally ventilated open-plan office buildings by using a simple approach that enabled us to survey many buildings simultaneously. All occupant responses were obtained during one afternoon. In a pre-experiment, temperature and the concentration of CO₂ were monitored in 2–10 locations/office to evaluate the variation throughout the offices. A representative measurement point was subsequently selected and measurements of the same parameters were made during one week. All offices were monitored during the same week and occupant responses to the indoor environment were collected via the internet on the same day within that week. The temperature and the CO₂ concentration varied more and were in some cases higher in the naturally ventilated buildings, but occupant responses in terms of symptoms and adverse perceptions differed only modestly between the two building types. Although rarely supported by statistical significance, the results indicated a somewhat higher degree of satisfaction with the indoor environment and a lower prevalence/intensity of symptoms among the occupants in the naturally ventilated buildings.     

The effects of outdoor air supply rate in an office on perceived air quality, sick building syndrome (SBS) symptoms and productivity

Perceived air quality, Sick Building Syndrome (SBS) symptoms and productivity were studied in a normally furnished office space (108 m3) ventilated with an outdoor airflow of 3, 10 or 30 L/s per person, corresponding to an air change rate of 0.6, 2 or 6 h-1. The temperature of 22 degrees C, the relative humidity of 40% and all other environmental parameters remained unchanged. Five groups of six female subjects were each exposed to the three ventilation rates, one group and one ventilation rate at a time. Each exposure lasted 4.6 h and took place in the afternoon. Subjects were unaware of the intervention and remained thermally neutral by adjusting their clothing. They assessed perceived air quality and SBS symptoms at intervals, and performed simulated normal office work. Increasing ventilation decreased the percentage of subjects dissatisfied with the air quality (P < 0.002) and the intensity of odour (P < 0.02), and increased the perceived freshness of air (P < 0.05). It also decreased the sensation of dryness of mouth and throat (P < 0.0006), eased difficulty in thinking clearly (P < 0.001) and made subjects feel generally better (P < 0.0001). The performance of four simulated office tasks improved monotonically with increasing ventilation rates, and the effect reached formal significance in the case of text-typing (P < 0.03). For each two-fold increase in ventilation rate, performance improved on average by 1.7%. This study shows the benefits for health, comfort and productivity of ventilation at rates well above the minimum levels prescribed in existing standards and guidelines. It confirms the results of a previous study in the same office when the indoor air quality was improved by decreasing the pollution load while the ventilation remained unchanged.     

Building-related symptoms and inflammatory potency of dust from office buildings

The aim was to investigate the association between building-related symptoms (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore, the association between dust potency and various building characteristics was investigated. Occupants of 22 office buildings received a retrospective questionnaire about BRS (2301 respondents). Dust was collected from groups of offices and building characteristics were recorded. The potency of a dust sample to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549 was measured as the slope of the initial linear part of the concentration-response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR = 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR = 1.5). No single symptoms correlated with the potency of surface dust. The PD was not related to single building factors. The inflammatory PD may be used as an integrated proxy measure of biologically active compounds in dust, reflecting health relevant properties of the dust. PRACTICAL IMPLICATIONS: The potency of surface dust may be used as a crude measurement of the chemical and biological exposures present in the building, and being associated with the development of central nervous system symptoms. However, additional research is needed to establish the predictive value of the potency of surface dust.     

Association of ventilation system type with SBS symptoms in office workers

This paper provides a synthesis of current knowledge about the associations of ventilation system types in office buildings with sick building syndrome (SBS) symptoms and discusses potential explanations for the associations. Most studies completed to date indicate that relative to natural ventilation, air conditioning, with or without humidification, was consistently associated with a statistically significant increase in the prevalence of one or more SBS symptoms, by approximately 30 to 200%. In two of three analyses from a single study (assessments), symptom prevalences were also significantly higher in air-conditioned buildings than in buildings with simple mechanical ventilation and no humidification. The available data also suggest, with less consistency, an increase in risk of symptoms with simple mechanical ventilation relative to natural ventilation. Insufficient information was available for conclusions about the potential increased risk of SBS symptoms with humidification or recirculation of return air. The statistically significant associations of mechanical ventilation and air conditioning with SBS symptoms are much more frequent than expected from chance and also not likely to be a consequence of confounding by several potential personal, job, or building-related confounders. Multiple deficiencies in HVAC system design, construction, operation, or maintenance, including some which cause pollutant emissions from HVAC systems, may contribute to the increases in symptom prevalences but other possible reasons remain unclear.     

Indoor air pollution from biomass combustion and respiratory symptoms of women and children in a Zimbabwean village

Rural areas of developing countries are particularly reliant on biomass for cooking and heating. Women and children in these areas are often exposed to high levels of pollutants from biomass combustion that is associated with a range of respiratory symptoms. Domestic exposure to carbon monoxide (CO) and respirable particles (RSPs) in association with respiratory symptoms among women and children in Zimbabwe was investigated in 48 households. Health status and household characteristics were also recorded. In this study, indoor levels of CO and RSPs exceeded World Health Organization (WHO) air quality guidelines in over 95% of kitchens. The level of indoor air pollutants was associated with the area of kitchen windows and the length of cooking time combined with the level of fire combustion. Prevalence of respiratory symptoms was 94% for women and 77% for children. In addition, women reporting respiratory symptoms were exposed to higher levels of RSPs when compared with those reporting no respiratory symptoms. The study results indicated that levels of indoor air pollutants in rural Zimbabwe may contribute to respiratory symptoms in both women and children. PRACTICAL IMPLICATIONS: Levels of respirable particles and carbon monoxide in kitchens in rural Zimbabwe are unacceptably high and measures to reduce levels should be undertaken. Based on the study findings, recommendations for increasing the area of kitchen windows may be considered as a practical method of reducing indoor air pollutants in rural Zimbabwe.     

The relationship between symptoms and blood pressure during maintenance hemodialysis

Intradialytic hypotension (IDH) is a detrimental complication of maintenance hemodialysis, but how it is defined and reported varies widely in the literature. European Best Practice Guideline and Kidney Disease Outcomes Quality Initiative guidelines require symptoms and a mitigating intervention to fulfill the diagnosis, but morbidity and mortality outcomes are largely based on blood pressure alone. Furthermore, little is known about the incidence of asymptomatic hypotension, which may be an important cause of hypoperfusion injury and impaired outcome. Seventy‐seven patients were studied over 456 dialysis sessions. Blood pressure was measured at 15‐minute intervals throughout the session and compared with post‐dialysis symptom questionnaire results using mixed modeling to adjust for repeated measures in the same patient. The frequency of asymptomatic hypotension was estimated by logistic regression using a variety of commonly cited blood pressure metrics that describe IDH. In 113 sessions (25%) where symptoms were recorded on the questionnaire, these appear not to have been reported to dialysis staff. When symptoms were reported (293 sessions [64%]), an intervention invariably followed. Dizziness and cramp were strongly associated with changes in systolic blood pressure (SBP), but not diastolic blood pressure. Nausea occurred more frequently in younger patients but was not associated with falls in blood pressure. Thresholds that maximized the probability of an intervention rather than a session remaining asymptomatic were SBP <100 mmHg or a 20% reduction in SBP from baseline. The probability of SBP falling to <100 mmHg in an asymptomatic session was 0.23. Symptoms are frequently not reported by patients who are hypotensive during hemodialysis, which leads to an underestimation of IDH if symptom‐based definitions are used. A revised definition of IDH excluding patient‐reported symptoms would be in line with literature reporting morbidity and mortality outcomes and include sessions in which potentially detrimental asymptomatic hypotension occurs.     

Teachers' work-related non-literature-known building-related symptoms are also connected to indoor toxicity: A cross-sectional study

A previous study showed that classical building-related symptoms (BRS) were related to indoor dust and microbial toxicity via boar sperm motility assay, a sensitive method for measuring mitochondrial toxicity. In this cross-sectional study, we analyzed whether teachers’ most common work-related non-literature-known BRS (nBRS) were also associated with dust or microbial toxicity. Teachers from 15 schools in Finland completed a questionnaire evaluating 20 nBRS including general, eye, respiratory, hearing, sleep, and mental symptoms. Boar sperm motility assay was used to measure the toxicity of extracts from wiped dust and microbial fallout samples collected from teachers’ classrooms. 231 teachers answered a questionnaire and their classroom toxicity data were recorded. A negative binomial mixed model showed that teachers’ work-related nBRS were 2.9-fold (95% CI: 1.2-7.3) higher in classrooms with highly toxic dust samples compared to classrooms with non-toxic dust samples (p = 0.024). The RR of work-related nBRS was 1.8 (95% CI: 1.1-2.9) for toxic microbial samples (p = 0.022). Teachers’ BRS appeared to be broader than reported in the literature, and the work-related nBRS were associated with toxic dusts and microbes in classrooms.