Outdoor Artificial Light at Night and Reproductive Endocrine and Glucose Homeostasis and Polycystic Ovary Syndrome in Women of Reproductive Age.

BACKGROUND: Artificial light at night, a well-recognized circadian clock disrupter, causes disturbances in endocrine homeostasis. However, the association of artificial light at night with polycystic ovary syndrome (PCOS) is still unknown. This study examines the effects of outdoor artificial light at night on sex hormones, glucose homeostasis markers, and PCOS prevalence in Anhui Province, China. METHODS: We recruited 20,633 women of reproductive age from Anhui Medical University Reproductive Medicine Center. PCOS was diagnosed according to Rotterdam criteria. We estimated long-term (previous year) and short-term (previous month) artificial light at night values for residential addresses using 500 m resolution satellite imagery. We fitted multivariable models, using both linear and logistic regression, to estimate the association of artificial light at night with sex hormones, glucose homeostasis markers, and PCOS prevalence. RESULTS: Both long-term and short-term exposure to outdoor artificial light at night were negatively associated with follicle-stimulating hormone and luteinizing hormone levels, while positively associated with testosterone, fasting insulin, homeostasis model assessment-insulin resistance, and homeostasis model assessment-insulin resistance-ß levels. The second-highest quintile of artificial light at night was associated with increased PCOS prevalence (odds ratio [OR long-term ] = 1.4; 95% confidence interval [CI] = 1.2, 1.6 and OR short-term = 1.3; 95% CI = 1.1, 1.5) compared with the lowest quintile. In addition, prevalence of PCOS was linearly associated with long-term exposure to artificial light at night, but nonlinearly associated with short-term exposure. This association was more evident in younger, obese or overweight, moderately educated, rural women, and for the summer and fall seasons. CONCLUSION: Outdoor artificial light at night may be a novel risk factor for PCOS.

Molecular mechanisms of artificial light at night affecting circadian rhythm disturbance.

Artificial light at night (ALAN) pollution has been regarded as a global environmental concern. More than 80% of the global population is exposed to light pollution. Exacerbating this issue, artificially lit outdoor areas are growing by 2.2% per year, while continuously lit areas have brightened by 2.2% each year due to rapid population growth and expanding urbanization. Furthermore, the increasing prevalence of night shift work and smart device usage contributes to the inescapable influence of ALAN. Studies have shown that ALAN can disrupt endogenous biological clocks, resulting in a disturbance of the circadian rhythm, which ultimately affects various physiological functions. Up until now, scholars have studied various disease mechanisms caused by ALAN that may be related to the response of the circadian system to light. This review outlines the molecular mechanisms by which ALAN causes circadian rhythm abnormalities in sleep disorders, endocrine diseases, cardiovascular disease, cancer, immune impairment, depression, anxiety and cognitive impairments.

Disaggregating the effects of daytime and nighttime light exposures on obesity, overweight, prostate and breast cancer morbidity worldwide.

Hormone-dependent cancers and overweight/obesity are not necessarily linked but might have similar underlying causes, such as circadian disruption, lack of physical activity, and unhealthy nutrition. Several empirical studies also attribute the rise in these types of morbidity to vitamin D deficiency, linked in turn to insufficient sunlight exposure. Other studies place an emphasis on melatonin (MLT) hormone suppression, associated with artificial light at night (ALAN) exposure. Yet no studies, carried out to date, have attempted to determine which of these environmental risk factors is associated stronger with the morbidity types in question. In this study, we aim to narrow this knowledge gap by analyzing data available for 100+ countries worldwide, while controlling ALAN and solar radiation exposure estimates by several potential confounders, such as GDPpc, GINI inequality index and unhealthy food consumption. As the study reveals, all the morbidity types under analysis are significantly and positively associated with ALAN exposure estimates (p < 0.05), while solar radiation appears to be significantly associated with prostate cancer rates only (p < 0.05), but not with breast cancer or overweight/obesity rates (p > 0.1). To the best of our knowledge, this study is the first that separates the effects of ALAN and daylight exposures on the abovementioned types of morbidity.

Retinal risk of endoillumination: A comparison of different ophthalmic illumination systems.

OBJECTIVES: In vitreoretinal surgery, there is always a conflict between bright illumination of the field of operation and retinal safety. This study aimed to investigate different light sources and light guides for their potential retinal risk due to bright illumination. METHODS: Irradiances in the fovea of ex-vivo porcine eyes resulting from different light sources (halogen lamp, xenon lamp and LED) and light guides are investigated for varying distances between the illumination tip and the fovea. The results are examined with regard to their photochemical and thermal retinal hazard and the maximal exposure time. The examination is carried out with the maximum intensity setting of each light source and with normalization to its brightness. MAIN RESULTS: With decreasing distance of the tip of the light source, the retinal hazard increases. The photochemical and thermal retinal hazard at maximum brightness are smallest for the halogen lamp, next for the xenon lamp and highest for the LED. Thus, the exposition time is the longest for the halogen lamp followed by the xenon lamp and the LED. Normalizing the results to the same brightness the maximum exposition time is nearly the same for xenon lamp and LED, but still higher in case of the halogen lamp. CONCLUSIONS: The choice of the most suitable lamp and illumination fiber depends on the intensity and spectral distribution of the illumination system. Concerning brightness, xenon and LED lamp are relatively harmless, but the surgeon should avoid the maximum device intensity.

Outdoor light at night and risk of liver cancer in the NIH-AARP diet and health study.

PURPOSE: Accumulating evidence suggests that light at night (LAN) disrupts circadian rhythms and may increase risk of liver cancer. However, there is no population-based study that examined LAN and liver cancer risk. Therefore, we aimed to investigate the association between outdoor LAN and liver cancer risk in a prospective cohort. METHODS: Residential outdoor LAN level was measured from satellite imagery in the NIH-AARP Diet and Health Study, a prospective cohort of 451,945 men and women, 50-71 years old. Relative risks (RR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models that adjusted for known risk factors for liver cancer and neighborhood characteristics. RESULTS: During an average 12.2 years of follow-up, 897 liver cancers, 603 of which were hepatocellular carcinomas (HCC), were diagnosed. Residential outdoor LAN was not associated with risk of liver cancer (RRQ5 vs Q1 = 0.96, 95% CI: 0.77-1.20, p trend = 0.771) or HCC (RRQ5 vs Q1 = 0.82, 95% CI: 0.62-1.07, p trend = 0.425). CONCLUSION: No association between outdoor LAN and risk of liver cancer or HCC may in part be due to limitations in LAN assessment. More studies on the relationship between light intensity, duration, timing, and wavelength and liver cancer are warranted.

Cardiopulmonary bypass in a child with erythropoietic protoporphyria.

Children with erythropoietic porphyria are generally under the care of paediatric dermatologists. When these children undergo major surgery, they are at risk of unusual complications due to their photosensitivity. Dermatologists may be consulted prior to surgery for advice. We describe a case of a child with erythropoietic porphyria undergoing open heart surgery, utilising an exchange transfusion alongside other strategies to minimise the risk of photosensitivity-induced haemolysis.

Digital asthenopia: blue-blocking lenses and + 0,40D additional power in the near zone, for eye strain, accommodation and convergence functions / Astenopia digital: avaliação de lentes com filtro de luz azul e poder adicional de +0,40D na zona de perto, para fadiga visual e nas funções de convergência e acomodação

ABSTRACT Purpose Evaluate blue-violet light filter and additional power of +0.40 D in the near zone ophthalmic lenses, on convergence, accommodative functions, and symptoms of digital asthenopia (DA). Methods Randomized study in cross-over design conducted on 49 volunteers (age, 29 ± 5.5 years; male: female, 18:31). Each subject wore test (+0.40 D in the near zone) and control lenses (regular single vision) for 4 weeks in randomized order. Both lenses had a selective blue-violet light filter. A baseline measurement was taken with the subjects' current updated glasses. Accommodation amplitude (AA) and near point of convergence (NPC) were measured binocularly with the RAF ruler. DA was evaluated by a questionnaire. Results No significant difference (p=.52) was found for AA comparing baseline (11.50±1.88 D), test (11.61± 1.62 D), and control SV lenses (11.88±1.50 D). No significant difference was found for NPC (p=.94), between baseline (6.50 ± 2.89cm), test (6.71± 3.49) and control SV lenses (6.82± 3.50 cm). No significant difference was found comparing test and control SV lenses in symptoms of DA (p=0.20). Conclusions The +0.40 D lenses have no negative impact on convergence or loss of accommodation power. The +0.40 D and control SV lenses had a similar impact on attenuating symptoms of DA.

RESUMO Objetivo Avaliar os efeitos do uso de lentes oftálmicas com filtro seletivo de luz azul-violeta, sem e com poder adicional de + 0,4D na zona de perto nas funções de acomodação e convergência e para sintomas de astenopia digital (AD). Métodos Ensaio clínico controlado, randomizado e mascarado, com 49 voluntários (idade, 29 ± 5,5 anos; masculino: feminino, 18: 31). Cada participante usou lentes de teste (+0,40 D na zona de perto) e controle (visão simples), por 4 semanas de forma randomizada. Ambas as lentes tinham filtro seletivo de luz azul-violeta. A medição inicial (baseline) foi feita com os óculos atualizados de cada participante. A amplitude de acomodação (AA) e o ponto de convergência próximo (PPC) foram medidos binocularmente com a régua RAF. A AD foi avaliada por um questionário. Resultados Não houve diferença estatisticamente significante (p=0,52) para as medidas de AA comparando as lentes baseline (11,50±1,88 D), teste (11,61±1,62 D) e controle VS (11,88±1,50 D). Nenhuma diferença significativa foi encontrada para a medida do PPC (p=0,94), entre as lentes baseline (6,50 ± 2,89cm), teste (6,71±3,49) e controle VS (6,82±3,50 cm). Nenhuma diferença significativa foi encontrada comparando lentes teste de VS e controle nos sintomas de AD (p=0,20). Conclusões As lentes com +0,40 D não têm impacto negativo na convergência ou na perda de acomodação. As lentes +0,40 D e controle VS, tiveram impacto semelhante na redução dos sintomas de AD.

Comparison of the effects of operating microscopes with light emitting diode and halogen light source on the eye: a rabbit study.

PURPOSE: To evaluate the potential toxicity of operation microscopes with halogen and light emitting diode (LED) light source on the rabbit eyes. MATERIALS AND METHODS: Thirty-two eyes of 16 male New Zealand pigmented rabbits were involved in the study. The rabbits were divided into two groups according to the type of light source applied. Only one eye of each rabbit was exposed to illumination light, unexposed fellow eyes served as the control group. Experimental groups included group 1 exposed to halogen light for 2 h and evaluated 1 day and 1 week after the illumination, group 2 exposed to LED light for two hours and evaluated 1 day and 1 week after the illumination. On the first and seventh days after exposing the light, we evaluated the rabbit corneas using in vivo confocal microscopy (IVCM). At the end of the seventh day, the Hematoxylin-eosin staining and TUNEL staining were performed to investigate the presence of apoptosis in the retina and retina pigment epithelium. RESULTS: Early IVCM findings revealed corneal epithelial cell ovalization and indistinct intercellular borders in the halogen light group. We also observed more increase in the keratocyte density index (23.7% vs 14.1%, p = 0.001, respectively) and the Bowman reflectivity index (12.4% vs 4.1%, p = 0.001, respectively) at first day of the light exposure in halogen light group compared to LED light group. However, late IVCM indicated that these findings disappeared one week later. No apoptosis was observed in the corneal and retinal layers in early and late examination groups. CONCLUSION: The present experimental study demonstrated that both halogen and LED lights, which were commonly used for microscopic eye surgery, had no sustained adverse effect on the cornea and retina of the rabbits; however, halogen light had a temporary adverse effect on corneal epithelium and stroma, which resolved within 1 week.

Associations between artificial light at night and risk for thyroid cancer: A large US cohort study.

BACKGROUND: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone-dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. METHODS: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. RESULTS: Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18-2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26-2.60) than men (HR, 1.29; 95% CI, 0.86-1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. CONCLUSIONS: LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms.

Ozone Generation by Ultraviolet Lamps†.

The COVID-19 pandemic has generated a great deal of interest in ultraviolet germicidal irradiation (UVGI) as an important means to disinfect air and surfaces. The traditional lamp employed for UVGI has been the low-pressure mercury-discharge lamp that emits primarily at 254 nm in the ultraviolet photobiological band UV-C (100-280 nm). The recent development of even shorter-wavelength UV-C lamps, such as the Krypton-Chloride, 222-nm lamp, has led to greater concerns about the UV-C generation of ozone. It is well known that wavelengths below 240 nm more readily generate ozone. However, there is a great misunderstanding with regard to the actual generation and dissipation of ozone molecules by UV-C lamps. A review of this subject is much warranted. An overview of the ozone generation of various UV-C light sources is presented to give users a better understanding of risk and how to assure control of ozone when employing UV-C lamps.

Light at Night and Risk of Pancreatic Cancer in the NIH-AARP Diet and Health Study.

Circadian disruption may play a role in carcinogenesis. Recent research suggests that light at night (LAN), a circadian disruptor, may be a risk factor for cancer. Moreover, LAN has been linked to obesity and diabetes, two risk factors for pancreatic ductal adenocarcinoma (PDAC). Here we examine the relationship between LAN and PDAC in an epidemiologic study of 464,371 participants from the NIH-AARP Diet and Health Study. LAN was estimated from satellite imagery at baseline (1996), and incident primary PDAC cases were ascertained from state cancer registries. Cox proportional hazards models were used to estimate HRs and two-sided 95% confidence intervals (CI) for the association between quintiles of LAN and PDAC in the overall population stratified by sex. Over up to 16.2 years of follow-up, a total of 2,502 incident PDAC were identified in the cohort. Higher estimated LAN exposure was associated with an elevated PDAC risk. Compared with those living in areas in the lowest LAN quintile, those in areas in the highest quintile had a 27% increase PDAC risk [HR (95% CI), 1.24 (1.03-1.49)], with similar risk for men [1.21 (0.96-1.53)] and women [1.28 (0.94-1.75)]. In addition, stronger associations were observed in normal and overweight groups compared with the obese group (P interaction = 0.03). Our results support the hypothesis that LAN and circadian disruption may be risk factors for PDAC. SIGNIFICANCE: Our study suggests that higher LAN is a risk factor for pancreatic cancer, contributing to the growing literature that demonstrates the potentially adverse health effects of light pollution.

Exposure to artificial light at night and risk of cancer: where do we go from here?

Despite experimental and mechanistic data suggesting circadian disruption's role in carcinogenesis, mixed findings from epidemiological investigations of artificial light at night and cancer risk in the general population are difficult to interpret due to exposure assessment limitations. It will be important for future studies to assess and validate individual-level exposures, ideally over the lifetime.

Evaluation of Potential Optical Radiation Hazards from LED Flashlights.

We performed optical radiation safety evaluations of LED flashlights to determine if they pose potential ocular hazards. Six commercially available flashlight samples were randomly selected from various vendors online. They were evaluated in accordance with specifications provided in the American National Standards Institute/Illuminating Engineering Society of North America (ANSI/IESNA) Standards RP 27.1 and RP 27.3. Four of the flashlights were found to have relatively high blue-light-weighted radiance values with short times (40 to 50 s) to reach the exposure limit specified in RP 27.1. These flashlights are in Risk Group 2 and present a moderate risk for retinal damage. Two of the flashlights are in Risk Group 1 and present a low risk for retinal damage. None of the flashlights present an ultraviolet (UV) radiation hazard or a retinal thermal hazard. Cautionary labeling on the packaging as required by RP 27.3 and on the flashlight handle is recommended for flashlights and on other handheld light sources that are in Risk Group 2 or Risk Group 3.

Association Between Outdoor Light-at-night Exposure and Colorectal Cancer in Spain.

BACKGROUND: Night-shift work, exposure to artificial light-at-night (ALAN) and particularly blue light spectrum, and the consequent circadian disruption may increase the risk of breast and prostate cancer. Colorectal cancer risk may also be increased among night-shift workers. We investigated the association between exposure to ALAN according to light spectrum and colorectal cancer among subjects who had never worked at night in a general population case-control study in Spain. METHODS: We examined information on 661 incident histologically verified colorectal cancer cases and 1,322 controls from Barcelona and Madrid, 2007-2013. Outdoor ALAN exposure was based on images from the International Space Station (ISS) including data on remotely sensed upward light intensity. We derived adjusted odds ratio (OR) estimates and confidence intervals (CI) for visual light, blue light, and spectral sensitivities of the five human photopigments assigned to participant's geocoded longest residence. RESULTS: Exposure to blue light spectrum was positively associated with colorectal cancer (OR = 1.6; 95% CI: 1.2-2.2; highest vs. lowest tertile). ORs were similar (OR = 1.7; 95% CI: 1.3-2.3) when further adjusting for area socioeconomic status, diet patterns, smoking, sleep, and family history. We observed no association for outdoor visual light (full spectrum) (OR = 1.0; 95% CI, 0.7-1.2; highest vs. lowest tertile). Analysis of the five photopigments gave similar results with increased risks for shorter wavelengths overlapping with the blue spectrum and no association for longer wavelengths. CONCLUSIONS: Outdoor blue light spectrum exposure that is increasingly prevalent in recent years may be associated with colorectal cancer risk. See video abstract: http://links.lww.com/EDE/B708.

Prospective Randomized Study on the Effects of Improved Sleep Quality After Craniotomy on Melatonin Concentrations and Inflammatory Response in Neurosurgical Intensive Care Patients.

OBJECTIVE: Sleep disorders in intensive care units after a craniotomy can decrease melatonin secretion and increase the inflammatory stress response. The aim of this study was to investigate the influence of improving sleep quality via eye patches and earplugs on melatonin secretion and inflammatory mediator release. METHODS: The study enrolled 41 patients who underwent craniotomy. Patients were randomized into 2 groups. "Group Intervention" received a sleep-promoting intervention with eye patches and earplugs to provide light and noise isolation, while "Group Control" received standard care. Blood levels of C-reactive protein and interleukin 1 and interleukin 6 along with urine levels of 6-sulphatoxymelatonin (aMT6) were measured preoperatively (baseline) and on postoperative days 1 and 3. Sleep quality was assessed with the Richards-Campbell Sleep Questionnaire. RESULTS: Sleep quality was higher in the intervention group (Richards-Campbell score:80.61 ± 11.96 vs. 33.50 ± 16.32; P < 0.001). Urine aMT6 levels increased significantly in the intervention group in spot urine samples from 10.15 (5.38-14.40) ng/mL at baseline to 14.52 (6.24-29.11) and 11.51 (7.88-29.05) ng/mL on postoperative days 1 and 3. They also increased in 24-hour urine samples from 25.73 (8.24-52.73) ng/mL at baseline to 35.38 (11.48-95.65) and 39.18 (2.36-125.23) ng/mL on postoperative days 1 and 3 (P = 0.001 and P = 0.005, respectively). The aMT6 concentration did not change significantly in the control group. The C-reactive protein concentrations increased postoperatively compared with baseline concentrations in both groups (P = 0.001 and P < 0.001). CONCLUSIONS: Melatonin secretion significantly increased as a result of improving postoperative sleep quality by noise and light isolation in neurosurgical intensive care unit patients after craniotomy.

Acute exposure to low-level light at night is sufficient to induce neurological changes and depressive-like behavior.

The advent and wide-spread adoption of electric lighting over the past century has profoundly affected the circadian organization of physiology and behavior for many individuals in industrialized nations; electric lighting in homes, work environments, and public areas have extended daytime activities into the evening, thus, increasing night-time exposure to light. Although initially assumed to be innocuous, chronic exposure to light at night (LAN) is now associated with increased incidence of cancer, metabolic disorders, and affective problems in humans. However, little is known about potential acute effects of LAN. To determine whether acute exposure to low-level LAN alters brain function, adult male, and female mice were housed in either light days and dark nights (LD; 14 h of 150 lux:10 h of 0 lux) or light days and low level light at night (LAN; 14 h of 150 lux:10 h of 5 lux). Mice exposed to LAN on three consecutive nights increased depressive-like responses compared to mice housed in dark nights. In addition, female mice exposed to LAN increased central tendency in the open field. LAN was associated with reduced hippocampal vascular endothelial growth factor-A (VEGF-A) in both male and female mice, as well as increased VEGFR1 and interleukin-1ß mRNA expression in females, and reduced brain derived neurotrophic factor mRNA in males. Further, LAN significantly altered circadian rhythms (activity and temperature) and circadian gene expression in female and male mice, respectively. Altogether, this study demonstrates that acute exposure to LAN alters brain physiology and can be detrimental to well-being in otherwise healthy individuals.

Light exposure from microscope versus intracameral illumination during cataract surgery.

Purpose: To evaluate light exposure from microscope versus intracameral illuminations to patient's and surgeon's retina during cataract surgery. Methods: Thirty consecutive patients who had cataract surgery using microscope and intracameral illuminations. At the point of the ocular of an operating microscope, optical illuminance and irradiance from the microscope illumination (60, 40, 20% intensity) and the intracameral illumination (60% intensity) were measured using a light meter and a spectrometer at a pause after lens capsule polishing in cataract surgery. Results: Average illuminance (lux) was 1.46, 0.66, 0.27, and 0.1 from 60%, 40%, 20% intensity microscope illuminations and 60% intracameral illumination. Average total spectral irradiance (µW/cm2) was 1.25, 0.65, 0.26, and 0.03 from 60%, 40%, 20% intensity microscope illuminations and 60% intracameral illumination. Conclusion: Microscope ocular illuminance and irradiance during cataract surgery were higher in the microscope illumination than in the intracameral illumination. It suggests that light exposure reaching patient's and surgeon's retina during cataract surgery is lower in the intracameral illumination than in the microscope illumination.

Surgical Fires and Burns: A 5-Year Analysis of Medico-legal Cases.

Surgical fires and unintended intraoperative burns cause serious patient harm, yet surveillance data are lacking in Canada. Medico-legal data provide unique descriptions of these events which can inform burn prevention strategies. We extracted 5 years of data on closed (2012-2016) medico-legal cases involving surgical fires and burns from the database of our organization which, in 2016, provided medico-legal support to >93,000 Canadian physicians. We performed a retrospective descriptive analysis of contributing factors using an in-house coding system and case reviews. We identified 53 eligible burn cases: 26 from thermal sources (49.1%), 16 from fires (30.2%), 5 from chemical sources (9.4%), and 6 from undetermined sources (11.3%). Common burn sources were electrosurgical equipment, lasers, lighting, and improper temperatures (causing thermal burns), cautery or lasers combined with supplemental oxygen and/or a flammable fuel source (causing fire), and improperly applied solutions including antiseptics (causing chemical burns). Nontechnical factors also contributed to patient outcomes, such as nonadherence to protocols (15 cases, 28.3%), failures in surgical team communication (3 cases, 5.7%), and lost situational awareness leading to delays in recognizing and treating burns (7 cases, 13.2%). This retrospective study highlights a need for improved surgical safety interventions to address surgical fires and burns. These interventions could include: effectively implemented surgical safety protocols, surgical team communication strategies, and raising awareness about preventing, diagnosing, and managing surgical burns.

The combined effects of occupational exposure to noise and other risk factors - a systematic review.

PURPOSE: Noise-induced health effects exacerbate by many other risk factors. This systematic review aims at shedding light on the combined effects of co-exposure to occupational noise and other factors. MATERIAL AND METHODS: A literature search in Web of Science, Scopus, PubMed, Science Direct, and Google Scholar, with appropriate keywords on combined effects of occupational noise, and co-exposure to noise and other factors, revealed 7928 articles which were screened by two researchers. A total of 775 articles were reviewed in full text. We found 149 articles that were relevant and had sufficient quality for analysis. RESULTS: We identified 16 risk factors that exacerbate occupational noise-induced health effects. These factors were classified into four groups: chemical (carbon monoxide (CO), solvents, heavy metals, and other chemicals), physical (lighting, heat, vibration, and cold), personal (age, gender, genetics, smoking, medication, contextual diseases) and occupational (workload and shift work). Hearing loss, hypertension, reduced performance, and cardiovascular strains, are the most important risk factors combined effects due to concurrent exposure to noise and other risk factors. CONCLUSION: Evidences of combined effects of solvents, vibration, heavy metals, CO, smoking, chemicals, aging, heat, and shiftwork were respectively stronger than for other factors. Most of the studies have investigated only the combined effects of risk factors on hearing, and the evidence for non-auditory effects is still limited, and more studies are warranted. Therefore, in the Hearing Conservation Programs, besides noise, aggravating factors of noise effects should also be taken into account.