Sleep duration and quality in permanent night work: an observational field study.

PURPOSE: Permanent night workers conceivably show better adaptation of circadian rhythms to night work than shift workers and therefore better possibilities of obtaining sufficient sleep of good quality after night shifts. We investigated the effect of night shifts including number of consecutive shifts on sleep among self-selected permanent night workers, and studied if the effect of night shifts differed between morning and evening types and compared with 3-shift workers. METHODS: The study population included 90 permanent night workers followed for 14 days (warehouse workers, 1228 observation days, 80% males). For comparison, we included 70 3-shift workers followed for 26 days (police officers, 1774 observation days, 100% men). Total sleep time (TST), primary sleep duration (PSD), and sleep efficiency were assessed by actigraphy. Measures of sleep quality and diurnal type were self-reported. RESULTS: Among permanent night workers, TST, PSD, difficulties falling asleep, disturbed sleep, and the number of awakenings decreased after night shifts compared with days without night work. Sleep efficiency, difficulties awakening, and non-refreshing sleep increased. More consecutive night shifts were associated with shorter TST and PSD. Sleep outcomes did not differ by diurnal type. Permanent night workers had fewer awakenings after night shifts than 3-shift workers, but no other differences were observed. CONCLUSION: This study does not provide evidence that supports recommendation of permanent night work to reduce adverse effects of night shifts on sleep. A limited number of consecutive night shifts is recommended to reduce accumulation of sleep debt.

Inbred Mouse Models in Cryptococcus neoformans Research.

Animal models are frequently used as surrogates to understand human disease. In the fungal pathogen Cryptococcus species complex, several variations of a mouse model of disease were developed that recapitulate different aspects of human disease. These mouse models have been implemented using various inbred and outbred mouse backgrounds, many of which have genetic differences that can influence host response and disease outcome. In this review, we will discuss the most commonly used inbred mouse backgrounds in C. neoformans infection models.

High Incidence of Cardiovascular Disease in Patients With Oesophageal Cancer-A Registry-Based Cohort Study.

BACKGROUND: The cardiovascular disease (CVD) burden among patients with oesophageal cancer (EC) treated with curative intent is unclear. AIM: To determine CVD incidence and all-cause mortality in patients with EC. METHOD: Danish national health registries were used to identify patients diagnosed with primary EC between 2008 and 2018. Each EC patient was matched with 10 individuals from the general population. The primary endpoint was a CVD hospital contact (CVD-HC), either admission or outpatient contact. Cox proportional hazard regression models were used to compare the risk of incident CVD-HCs between the cohorts. RESULTS: The study included 1,525 patients with EC and 15,250 individuals from the general population. Patients with EC had a post-diagnosis one-year adjusted hazard ratio (HR) of CVD-HC of 6.1 (95% confidence intervals [CIs] 5.6-6.8) compared with the general population. During the next nine years, the risk of CVD-HC was comparable between the two cohorts, with an adjusted HR of 1.0 (95% CI 0.9-1.3). Patients with EC, and particularly those with prevalent CVD, had a high risk of atrial fibrillation, ischaemic heart disease, and venous thromboembolism within the first year after EC diagnosis. Prevalent CVD among patients with EC was not associated with higher mortality. CONCLUSIONS: CVD morbidity was transiently increased in the first year following EC diagnosis compared with the general population. All-cause mortality risks were high but did not appear to be affected by prevalent CVD. The very high risk of CVD in patients with primary EC to be treated with curative intent calls for healthcare initiatives to advance preventive and post-treatment strategies.

The Danish child and parent Gait Outcomes Assessment List questionnaires were reliable and valid for cerebral palsy.

AIM: We investigated the reliability and validity of the Danish child and parent versions of the Gait Outcomes Assessment List (GOAL) questionnaires for ambulatory children with cerebral palsy (CP). METHODS: Translation and cultural adaptations were performed and content validity evaluated. Participants were enrolled between 2016 and 2018 from Aarhus University Hospital, Denmark. Children and parents completed the GOAL questionnaires twice for test-retest reliability. Discriminative validity was evaluated by comparing the child and parent GOAL scores between children with Gross Motor Function Classification System (GMFCS) levels I and II. The concurrent validity of the GOAL questionnaires were investigated by comparing them with Challenge-20, which assesses motor skills in children with CP. RESULTS: We studied 59 children (57% boys) with CP and GMFCS I-II at a mean age of 10.6 years. Test-retest intra-class correlations were excellent for the children (0.91, 95% confidence interval (CI) 0.83-0.96) and good for the parents (0.83, 95% CI 0.67-0.91). GOAL scores decreased with increasing GMFCS (p < 0.05). Both versions correlated well. The mean children's scores were significantly (6.2/100) higher than the parents' (p < 0.001). The GOAL scores correlated positively with Challenge-20. CONCLUSION: The Danish GOAL child and parent questionnaires demonstrated good reliability and content and discriminative and concurrent validity.

Hip displacements and correctable scoliosis were prevalent in children with cerebral palsy registered in a Danish follow-up programme from 2010 to 2020.

AIM: We need a better understanding of non-surgical interventions for hip dislocations and scoliosis. This study estimated the cumulative incidence of problems among children with cerebral palsy and described the type and frequency of therapist-led interventions. METHODS: The study comprised 1482 children (58% male) aged 0-15 years, with a mean age of 3.6 years, who were registered in the Danish Cerebral Palsy Follow-up Programme from 2010 to 2020. We used the Kaplan-Meier estimator to examine the cumulative incidence of hip displacement, hip dislocation, correctable scoliosis and non-correctable scoliosis. The type and frequency of therapist-led interventions are reported descriptively. RESULTS: The cumulative incidence of hip displacement and hip dislocation were 15.8% and 3.5%, respectively, and 39.0% and 13.9% for correctable and non-correctable scoliosis. The most frequently reported type of therapist-led intervention was a joint range of motion exercise. We found that 60.5% with hip displacements and 43.8% with correctable scoliosis used a standing aid. A further 5.4% used a spinal orthosis to prevent deformity and 8.1% for stabilisation. CONCLUSION: Hip displacement and correctable scoliosis were prevalent in children with cerebral palsy, whereas the occurrence of hip dislocations and non-correctable scoliosis was low. The use of assistive aids was low.

5-Flucytosine Longitudinal Antifungal Susceptibility Testing of Cryptococcus neoformans: A Substudy of the EnACT Trial Testing Oral Amphotericin.

Background: The EnACT trial was a phase 2 randomized clinical trial conducted in Uganda, which evaluated a novel orally delivered lipid nanocrystal (LNC) amphotericin B in combination with flucytosine for the treatment of cryptococcal meningitis. When flucytosine (5FC) is used as monotherapy in cryptococcosis, 5FC can induce resistant Cryptococcus mutants. Oral amphotericin B uses a novel drug delivery mechanism, and we assessed whether resistance to 5FC develops during oral LNC-amphotericin B therapy. Methods: We enrolled Ugandans with HIV diagnosed with cryptococcal meningitis and who were randomized to receive 5FC and either standard intravenous (IV) amphotericin B or oral LNC-amphotericin B. We used broth microdilution to measure the minimum inhibitory concentration (MIC) of the first and last cryptococcal isolates in each participant. Breakpoints are inferred from 5FC in Candida albicans. We measured cerebral spinal fluid (CSF) 5FC concentrations by liquid chromatography and tandem mass spectrometry. Results: Cryptococcus 5FC MIC50 was 4 µg/mL, and MIC90 was 8 µg/mL. After 2 weeks of therapy, there was no evidence of 5FC resistance developing, defined as a >4-fold change in susceptibility in any Cryptococcus isolate tested. The median CSF 5FC concentration to MIC ratio (interquartile range) was 3.0 (1.7-5.5) µg/mL. There was no association between 5FC/MIC ratio and early fungicidal activity of the quantitative rate of CSF yeast clearance (R2 = 0.004; P = .63). Conclusions: There is no evidence of baseline resistance to 5FC or incident resistance during combination therapy with oral or IV amphotericin B in Uganda. Oral amphotericin B can safely be used in combination with 5FC.

History of working conditions and the risk of old-age dependency: a nationwide Swedish register-based study.

AIMS: There is substantial evidence that previous working conditions influence post-retirement health, yet little is known about previous working conditions' association with old-age dependency. We examined job strain, hazardous and physical demands across working life, in relation to the risk of entering old-age dependency of care. METHODS: Individually linked nationwide Swedish registers were used to identify people aged 70+ who were not receiving long-term care (residential care or homecare) at baseline (January 2014). Register information on job titles between the years 1970 and 2010 was linked with a job exposure matrix of working conditions. Random effects growth curve models were used to calculate intra-individual trajectories of working conditions. Cox regression models with age as the timescale (adjusted for living situation, educational attainment, country of birth, and sex) were conducted to estimate hazard ratios for entering old-age dependency during the 24 months of follow-up (n = 931,819). RESULTS: Having initial adverse working conditions followed by an accumulation throughout working life encompassed the highest risk of entering old-age dependency across the categories (job strain: HR 1.23, 95% CI 1.19-1.27; physical demands: HR 1.36, 95% CI 1.31-1.40, and hazardous work: HR 1.35, 95% CI 1.30-1.40). Initially high physical demands or hazardous work followed by a stable trajectory, or initially low-level physical demand or hazardous work followed by an accumulation throughout working life also encompassed a higher risk of dependency. CONCLUSIONS: A history of adverse working conditions increased the risk of old-age dependency. Reducing the accumulation of adverse working conditions across the working life may contribute to postponing old-age dependency.

Ankle-foot orthoses among children with cerebral palsy: a cross-sectional population-based register study of 8,928 children living in Northern Europe.

BACKGROUND: Cerebral palsy (CP) is an umbrella term where an injury to the immature brain affects muscle tone and motor control, posture, and at times, the ability to walk and stand. Orthoses can be used to improve or maintain function. Ankle-foot orthoses (AFOs) are the most frequently used orthoses in children with CP. However, how commonly AFOs are used by children and adolescents with CP is still unknown. The aims of this study were to investigate and describe the use of AFOs in children with CP in Sweden, Norway, Finland, Iceland, Scotland, and Denmark, and compare AFO use between countries and by gross motor function classification system (GMFCS) level, CP subtype, sex, and age. METHOD: Aggregated data on 8,928 participants in the national follow-up programs for CP for the respective countries were used. Finland does not have a national follow-up program for individuals with CP and therefore a study cohort was used instead. Use of AFOs were presented as percentages. Logistic regression models were used to compare the use of AFOs among countries adjusted for age, CP subtype, GMFCS level, and sex. RESULTS: The proportion of AFO use was highest in Scotland (57%; CI 54-59%) and lowest in Denmark (35%; CI 33-38%). After adjusting for GMFCS level, children in Denmark, Finland, and Iceland had statistically significantly lower odds of using AFOs whereas children in Norway and Scotland reported statistically significantly higher usage than Sweden. CONCLUSION: In this study, the use of AFOs in children with CP in countries with relatively similar healthcare systems, differed between countries, age, GMFCS level, and CP subtype. This indicates a lack of consensus as to which individuals benefit from using AFOs. Our findings present an important baseline for the future research and development of practical guidelines in terms of who stands to benefit from using AFOs.

Does it matter for health if steps are taken during work or leisure? A prospective accelerometer study using register-based long-term sickness absence.

BACKGROUND: Walking is known to be good for health. However, it is unknown whether it matters if steps are taken during work or leisure. Therefore, we aimed to examine the prospective association between accelerometer-measured steps taken during work or leisure and register-based long-term sickness absence (LTSA). METHODS: We included 937 blue- and white-collar workers from the PODESA cohort who wore a thigh-based accelerometer over four days to measure number of steps during work and leisure. Steps were divided into domain based on diary data. First event of LTSA was retrieved from a national register with four years' follow-up. We used Cox proportional hazard models to analyze the association between domain-specific and total daily steps and LTSA, adjusted for age, sex, job type, smoking, and steps in the other domain (e.g., work/leisure). RESULTS: We found more steps at work to be associated with a higher LTSA risk [Hazard Ratio (HR):1.04; 95% CI: 1.00-1.08 per 1000 steps]. No significant association was found between steps during leisure and LTSA (HR: 0.97; 95% CI: 0.91-1.02), nor between total daily steps and LTSA (HR: 1.01; CI 95% 0.99-1.04). CONCLUSIONS: More steps at work were associated with higher risk of LTSA, while steps during leisure was not clearly associated with LTSA risk. These findings partly support 'the physical activity paradox' stating that the association between physical activity and health depends on the domain.

Importance of Clinical Isolates in Cryptococcus neoformans Research.

The human pathogenic fungus Cryptococcus neoformans is a global health concern. Previous research in the field has focused on studies using reference strains to identify virulence factors, generate mutant libraries, define genomic structures, and perform functional studies. In this review, we discuss the benefits and drawbacks of using reference strains to study C. neoformans, describe how the study of clinical isolates has expanded our understanding of pathogenesis, and highlight how studies using clinical isolates can further develop our understanding of the host-pathogen interaction during C. neoformans infection.

Radiation dose to heart and cardiac substructures and risk of coronary artery disease in early breast cancer patients: A DBCG study based on modern radiation therapy techniques.

BACKGROUND: Coronary artery disease (CAD) has been reported as a late effect following radiation therapy (RT) of early breast cancer (BC). This study aims to report individual RT doses to the heart and cardiac substructures in patients treated with CT-based RT and to investigate if a dose-response relationship between RT dose and CAD exists using modern radiation therapy techniques. METHODS: Patients registered in the Danish Breast Cancer Group database from 2005 to 2016 with CT-based RT were eligible. Among 15,765 patients, the study included 204 with CAD after irradiation (cases) and 408 matched controls. Individual planning CTs were retrieved, the heart and cardiac substructures were delineated and dose-volume parameters were extracted. RESULTS: The median follow-up time was 7.3 years (IQR: 4.6-10.0). Among cases, the median mean heart dose was 1.6 Gy (IQR 0.2-6.1) and 0.8 Gy (0.1-2.9) for left-sided and right-sided patients, respectively (p < 0.001). The highest RT doses were observed in the left ventricle and left anterior descending coronary artery for left-sided RT and in the right atrium and the right coronary artery after right-sided RT. The highest left-minus-right dose-difference was located in the distal part of the left anterior descending coronary artery where also the highest left-versus-right ratio of events was observed. However, no significant difference in the distribution of CAD was observed by laterality. Furthermore, no significant differences in the dose-volume parameters were observed for cases versus controls. CONCLUSIONS: CAD tended to occur in the part of the heart with the highest left-minus- right dose difference, however, no significant risk of CAD was observed at 7 years' median follow-up.

Prevalence of knee contractures is high in children with cerebral palsy in Denmark.

INTRODUCTION: Cerebral palsy (CP) is a neurological disease occurring in children at early gestation, often resulting in pronounced functional limitations. A Swedish cross-sectional study (Cloodt, et al., 2018) discovered that 22% of children with CP had a knee contracture, which was associated with higher levels of Gross Motor Function Classification System (GMFCS), higher age, and higher levels of spasticity measured by the Modified Ashworth Scale (MAS). The current study investigated these associations in a Danish population. METHODS: This is a cross-sectional study including 1,163 children with CP aged 0-15 years, registered in the Danish National Cerebral Palsy Registry between 2017 and 2019. Prevalence of knee contracture was estimated, and logistic regression analysis was applied with results presented as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: A total of 511 children with CP had knee contracture resulting in a prevalence of 44%. Age groups 4-6 years (OR: 1.73, CI: 1.19; 2.52), 7-9 years (OR: 1.85, CI: 1.29; 2.66) and 10-12 years (OR: 2.12, CI: 1.39; 3.24) were significantly associated with a higher prevalence of knee contractures compared to age group 0-3 years. Knee contractures were significantly more frequent at GMFCS levels IV (OR: 1.9, CI: 1.21; 2.97) and V (OR: 3.62, CI: 2.36; 5.55) compared to level I. Knee contractures were not associated with higher levels of MAS. CONCLUSIONS: Knee contractures are highly prevalent and significantly associated with high levels of GMFCS and increased age until 12 years, but not with high levels of spasticity in children with CP in Denmark.

MinION Whole-Genome Sequencing in Resource-Limited Settings: Challenges and Opportunities.

Purpose of Review: The introduction of MinION whole-genome sequencing technology greatly increased and simplified complete genome sequencing in various fields of science across the globe. Sequences have been generated from complex organisms to microorganisms and are stored in genome databases that are readily accessible by researchers. Various new software for genome analysis, along with upgrades to older software packages, are being generated. New protocols are also being validated that enable WGS technology to be rapidly and increasingly used for sequencing in field settings. Recent Findings: MinION WGS technology has been implemented in developed countries due to its advantages: portability, real-time analysis, and lower cost compared to other sequencing technologies. While these same advantages are critical in developing countries, MinION WGS technology is still under-utilized in resource-limited settings. Summary: In this review, we look at the applications, advantages, challenges, and opportunities of using MinION WGS in resource-limited settings.

Heart rate variability during sleep after two, four and seven consecutive night shifts and recovery days: a cross-over intervention study.

OBJECTIVE: Recovery after shift work is an important part reducing the health problems related to shift work. Heart rate variability (HRV) is an indicator of the balance between sympathetic and parasympathetic activity in the autonomic nervous system and can be used as a measure of recovery after night shifts. The aim of the study is to investigate autonomic recovery during sleep in response to night work in a crossover intervention study. METHODS: Seventeen male police officers working in call centres in five different police district participated in the HRV measurements. The participants were exposed to three interventions: 2 + 2: two consecutive night shifts followed by two consecutive day recovery days; 4 + 4: four consecutive night shifts followed by four consecutive recovery days; 7 + 7: seven consecutive night shifts followed by seven consecutive recovery days. On the last day with night shift and the last recovery day in each intervention the participants underwent 24 h HRV recordings. We analysed HRV during sleep. The five 5-min intervals with the lowest heart rate during each sleep period were chosen for spectral analysis of the heart interbeat interval time series. The five 5-min intervals could occur at any time during sleep. RESULTS: There were overall differences in HRV during sleep between days with night shifts and recovery days, primarily in parasympathetic activity. There was no difference in the lowest heart rate obtained, but the timing was different for the three interventions. The lowest heart rate after night shifts occurred 112 (SD 79) min, 174 (SD 115) min and 135 (SD 94) min after sleep onset for the 2 + 2 night shift, the 4 + 4 night shift and the 7 + 7 night shift, respectively. CONCLUSION: Overall sleep-related autonomic recovery had higher parasympathetic modulation of cardiac rhythm on the 2 + 2 shift system compared to the 4 + 4 and 7 + 7 shift system.

Cryptococcus neoformans Genotypic Diversity and Disease Outcome among HIV Patients in Africa.

Cryptococcal meningoencephalitis, a disease with poor patient outcomes, remains the most prevalent invasive fungal infection worldwide, accounting for approximately 180,000 deaths each year. In several areas of sub-Saharan Africa with the highest HIV prevalence, cryptococcal meningitis is the leading cause of community-acquired meningitis, with a high mortality among HIV-infected individuals. Recent studies show that patient disease outcomes are impacted by the genetics of the infecting isolate. Yet, there is still limited knowledge of how these genotypic variations contribute to clinical disease outcome. Further, it is unclear how the genetic heterogeneity of C. neoformans and the extensive phenotypic variation observed between and within isolates affects infection and disease. In this review, we discuss current knowledge of how various genotypes impact disease progression and patient outcome in HIV-positive populations in sub-Saharan African, a setting with a high burden of cryptococcosis.

How Risk Management During COVID-19 Influences Eldercare Personnel's Perceptions of Their Work Environment.

OBJECTIVE: To investigate the association between workplace COVID-19 (coronavirus disease 2019) risk management and eldercare workers' perception of their social environment at work. METHODS: Cross-sectional questionnaire data from 952 participants were collected by the Danish labor union, FOA, and analyzed using multinomial logistic regression. RESULTS: Unclear guidelines, insecurity regarding organization of work, lack of attention to vulnerable employees, and lack of instruction in the use of personal protective equipment were associated with perceived negative changes in the social environment at work. Also, higher local incidence rates of SARS-CoV-2 infections were associated with a weaker sense of community (odds ratio, 1.18; 95% confidence interval, 1.04-1.36). CONCLUSIONS: These findings indicate that risk management is important not only for prevention of infection but also for individual and workplace resilience toward external demands and health threats.

Lack of Association between Fluconazole Susceptibility and ERG11 Nucleotide Polymorphisms in Cryptococcus neoformans Clinical Isolates from Uganda.

Fluconazole is the drug of choice for cryptococcal meningitis (CM) monoprophylaxis in resource-limited settings such as Uganda. Emerging fluconazole resistance linked to mutations in the Cryptococcus neoformansERG11 gene (CYP51) has been observed in clinical isolates. Currently, the single nucleotide polymorphisms [SNPs] in the Cryptococcus spp. ERG11 gene that could be responsible for fluconazole resistance are poorly characterized within Ugandan C. neoformans clinical isolates. If available, this information would be useful in the management of cryptococcosis among HIV patients. This cross-sectional study investigates the SNPs present in the coding region of the C. neoformansERG11 gene to determine the relationship between the SNPs identified and fluconazole susceptibility of the clinical isolates. 310 C. neoformans isolates recovered from the Cerebrospinal Fluid (CSF) of patients with HIV and cryptococcal meningitis were examined. The fluconazole half-maximal inhibitory concentrations (IC50 range: 0.25−32 µg/mL) was determined using the microbroth dilution method. A total of 56.1% of the isolates had low IC50 values of <8 µg/mL while 43.9% had high IC50 values ≥ 8 µg/mL. We amplified and sequenced 600 bp of the ERG11 coding sequence from 40 of the clinical isolates. Novel synonymous and 2 missense mutations, S460T and A457V, were identified in the ERG11 gene. The identified SNPs were not associated with differences in fluconazole IC50 values in vitro (p = 0.179).

Educational attainment in young adulthood and self-rated health in midlife - Does allostatic load mediate the association?

This study aimed to examine the extent to which allostatic load (AL), measured in midlife, mediates the association between educational attainment in young adulthood and self-rated health (SRH) in midlife among women and men. The study used data from the Copenhagen Aging and Midlife Biobank (CAMB; n = 5467 participants, aged 48-62 years, 31.5% women). Educational attainment was assessed as years of education. SRH was assessed with one item: 'In general, how would you say your health is?' with response options from "excellent" to "poor". AL mediated 31.7% and 19.7% of the association between educational attainment and SRH in women and men, respectively. We observed that higher educational attainment was associated with better SRH and lower AL in both women and men. Our study showed that AL partly mediates the association between educational attainment in young adulthood and SRH in adulthood among both men and women. This study indicates that educational attainment in young adulthood affects health throughout life. Such knowledge of a potential mediator may be important in breaking the social heritage.

Reduction in myocardial function and oxygen consumption after chemoradiotherapy in patients with esophageal cancer.

BACKGROUND: Chemoradiotherapy (CRT) may induce myocardial dysfunction, congestive heart failure, and impaired physical performance in patients with esophageal cancer (EC). We aimed to investigate left ventricular (LV) function at rest and during stress, using echocardiography (echo) and a cardiopulmonary exercise (CPX) test both before and immediately after completing CRT. MATERIAL AND METHODS: Consecutive EC patients referred for curative treatment were enrolled. Patients attended either definitive CRT or neoadjuvant CRT with subsequent surgery. The evaluation included cardiac biomarkers, electrocardiogram, echo, and CPX test. The primary endpoint was changes in left ventricular (LV) global longitudinal strain (GLS) at rest. Secondary endpoints were LV ejection fraction (LVEF), LV diastolic function, LVEF and GLS at peak exercise, and maximal oxygen consumption (VO2max). The trial was registered with ClinicalTrials.gov (NCT03619317). RESULTS: Among 47 patients enrolled (94% male; median age 67 years, range 50-86 years), cardiac examinations were performed a median of three days [Interquartile range (IQR (1-5))] before CRT and one day [IQR (0-6)] after CRT. At rest, GLS and LVEF decreased, 17.6 vs. 16.4% and 56.4 vs. 55.1%, respectively (p = 0.004; p = 0.030). Furthermore, an absolute decrease of at least 5% in LVEF and 2.5% in GLS was noted in 21% of the patients. Signs of LV diastolic dysfunction increased from 13 to 21% (p = ns). VO2max significantly decreased; 21.2 ml/kg/min vs. 18.8 ml/kg/min (p < 0.001). CONCLUSION: LV function and physical performance decreased in EC patients after CRT, and the LV systolic reserve capacity declined. This study highlighted that EC treatment was associated with early cardiac side effects, which may have clinical and prognostic implications.

The role of combined modifiable lifestyle behaviors in the association between exposure to stressors and allostatic load: A systematic review of observational studies.

BACKGROUND: Exposure to stressors can evoke psychological, physiological, and behavioral stress responses, which may lead to the adoption of health-damaging behaviors that dysregulate multiple biological systems contributing to a high allostatic load. This review explored the role of combined modifiable lifestyle behaviors in the relationship between stressors and allostatic load among healthy adults. METHODS: A systematic search was conducted in Medline Complete, PsycINFO, CINAHL, and Embase databases up to September 2021. The PRISMA guidelines guided reporting and study quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist. RESULTS: Database searches identified 319 papers. Eight cross-sectional and two longitudinal studies met our inclusion criteria. Among the ten studies, combined modifiable lifestyle behaviors partly explained the association between exposure to stressors and elevated allostatic load in four cross-sectional and two longitudinal studies. CONCLUSION: Some evidence suggests that combined modifiable lifestyle behaviors may help explain the relationship between stressors and an elevated allostatic load. Further longitudinal studies with mediation analyses would strengthen these findings and help to confirm the mechanistic role of combined modifiable lifestyle behaviors underlying the relationship between stress exposure and allostatic load.