Work hours, weekend working, nonstandard work schedules and sleep quantity and quality: findings from the UK household longitudinal study.

BACKGROUND: Atypical temporal work patterns such as working longer than the standard 35-40 h/ week, weekend working, and nonstandard work schedules (i.e. outside of the typical 9-5, including but not restricted to shiftwork) are increasingly prevalent in the UK. Aside from occupation-specific studies, little is known about the effects of these atypical temporal work patterns on sleep among workers in the UK, even though poor sleep has been linked to adverse health problems, lower workplace productivity, and economic costs. METHOD: We used regression models to investigate associations between three types of atypical temporal work patterns (long and short weekly work hours, weekend working, and nonstandard schedules) and sleep duration and disturbance using data from over 25,000 employed men and women from 2012-2014 and/or 2015-2017 in the UK Household Longitudinal Study, adjusting for potential confounders and psychosocial work factors. RESULTS: We found that relative to a standard 35-40 h/week, working 55 h/week or more was related to short sleep (less than 7 h/night) and sleep disturbance. Working most/all weekends compared to non-weekends was associated with short sleep, long sleep (more than 8 h/night), and sleep disturbance, as was working nonstandard schedules relative to standard schedules (fixed day-time schedules). Further analyses suggested some gender differences. CONCLUSIONS: These results should prompt employers and policymakers to recognise the need for rest and recovery, consider how the timing and scheduling of work might be improved to better support workers' health and productivity, and consider appropriate compensation for anyone required to work atypical temporal work patterns.

Abrupt permafrost thaw drives spatially heterogeneous soil moisture and carbon dioxide fluxes in upland tundra.

Permafrost thaw causes the seasonally thawed active layer to deepen, causing the Arctic to shift toward carbon release as soil organic matter becomes susceptible to decomposition. Ground subsidence initiated by ice loss can cause these soils to collapse abruptly, rapidly shifting soil moisture as microtopography changes and also accelerating carbon and nutrient mobilization. The uncertainty of soil moisture trajectories during thaw makes it difficult to predict the role of abrupt thaw in suppressing or exacerbating carbon losses. In this study, we investigated the role of shifting soil moisture conditions on carbon dioxide fluxes during a 13-year permafrost warming experiment that exhibited abrupt thaw. Warming deepened the active layer differentially across treatments, leading to variable rates of subsidence and formation of thermokarst depressions. In turn, differential subsidence caused a gradient of moisture conditions, with some plots becoming consistently inundated with water within thermokarst depressions and others exhibiting generally dry, but more variable soil moisture conditions outside of thermokarst depressions. Experimentally induced permafrost thaw initially drove increasing rates of growing season gross primary productivity (GPP), ecosystem respiration (Reco ), and net ecosystem exchange (NEE) (higher carbon uptake), but the formation of thermokarst depressions began to reverse this trend with a high level of spatial heterogeneity. Plots that subsided at the slowest rate stayed relatively dry and supported higher CO2 fluxes throughout the 13-year experiment, while plots that subsided very rapidly into the center of a thermokarst feature became consistently wet and experienced a rapid decline in growing season GPP, Reco , and NEE (lower carbon uptake or carbon release). These findings indicate that Earth system models, which do not simulate subsidence and often predict drier active layer conditions, likely overestimate net growing season carbon uptake in abruptly thawing landscapes.

Challenges and opportunities for overcoming dog use in agrochemical evaluation and registration.

Progress in developing new tools, assays, and approaches to assess human hazard and health risk provides an opportunity to re-evaluate the necessity of dog studies for the safety evaluation of agrochemicals. A workshop was held where partic­ipants discussed the strengths and limitations of past use of dogs for pesticide evaluations and registrations. Opportunities were identified to support alternative approaches to answer human safety questions without performing the required 90-day dog study. Development of a decision tree for determining when the dog study might not be necessary to inform pesticide safety and risk assessment was proposed. Such a process will require global regulatory authority participation to lead to its acceptance. The identification of unique effects in dogs that are not identified in rodents will need further evaluation and determination of their relevance to humans. The establishment of in vitro and in silico approaches that can provide critical data on relative species sensitivity and human relevance will be an important tool to advance the decision process. Promising novel tools including in vitro comparative metabolism studies, in silico models, and high-throughput assays able to identify metabolites and mechanisms of action leading to development of adverse outcome pathways will need further development. To replace or eliminate the 90-day dog study, a collaborative, multidisciplinary, international effort that transcends organi­zations and regulatory agencies will be needed in order to develop guidance on when the study would not be necessary for human safety and risk assessment.

Compression Therapy Is Cost-Saving in the Prevention of Lower Limb Recurrent Cellulitis in Patients with Chronic Edema.

Background: Cellulitis is a common and often recurrent infection that causes substantial financial burden and morbidity. Compression therapy reduces the risk of recurrent cellulitis episodes for adults with chronic edema; however, little is known about the cost-effectiveness of the intervention. Methods and Results: A cost analysis was undertaken during a randomized controlled trial (RCT) involving 84 participants with lower limb chronic edema and a history of recurrent cellulitis. The intervention group received compression therapy and education, while the control group received education only. A clinical audit and survey were used to measure health service and patient resource use for (1) the most recent episode of cellulitis, and (2) compression therapy over 18 months. Australian reference costs were used to calculate cellulitis and compression therapy costs, and the mean expenditure in both the RCT groups. Of the 84 RCT participants, 43 were surveyed and audited on the cost of cellulitis, and 40 on the cost of compression therapy. The mean cost of a hospitalized and nonhospitalized episode of cellulitis was $9071 and $506 from a health service perspective, and $4496 and $1320 from a patient perspective. The mean cost of compression therapy per participant over 18 months was $1905 and $421 from health service and patient perspectives, respectively. During the RCT, the mean annual cost per participant was $4972 in the experimental group and $26,382 in the control group, giving a cost-saving of $21,483 (95% confidence interval, 3136-48,176) per participant. Conclusion: For patients with lower limb chronic edema and recurrent cellulitis, compression therapy is both efficacious and cost-saving. Trial Registration: ACTRN12617000412336.

Factors affecting the implementation of a complex health intervention to improve insulin management in primary care: A SWOT analysis.

BACKGROUND:  In South Africa, initiating and managing insulin in primary care for people living with type 2 diabetes (PLWD) is a major challenge. To address these challenges, a multidisciplinary team from the University of Pretoria (South Africa) developed the Tshwane Insulin project (TIP) intervention. AIM:  To determine internal and external factors, either facilitators or barriers, that could influence the implementation of the TIP intervention and propose strategies to ensure sustainability. SETTING:  Tshwane District, Gauteng province, South Africa. METHODS:  We used the SWOT framework to qualitatively analyse the strengths, weaknesses, opportunities, and threats influencing the implementation of the TIP intervention. Four field researchers and three managers from the TIP team participated in an online group discussion. We also conducted semi-structured interviews with healthcare providers (HCPs) (seven nurses, five doctors) and patients with type 2 diabetes (n = 13). RESULTS:  Regardless of the identified weaknesses, the TIP intervention was accepted by PLWD and HCPs. Participants identified strengths including app-enabled insulin initiation and titration, pro-active patient follow-up, patient empowerment and provision of glucose monitoring devices. Participants viewed insulin resistance and the attitudes of HCPs as potential threats. Participants suggested that weaknesses and threats could be mitigated by translating education material into local languages and using the lived experiences of insulin-treated patients to address insulin resistance. The procurement of glucose monitoring devices by national authorities would promote the sustainability of the intervention. CONCLUSION:  Our findings may help decision-makers and health researchers to improve insulin management for PLWD in resource-constrained settings by using telehealth interventions.

Assessing barriers to insulin therapy among people with type 2 diabetes in South Africa using the Insulin Treatment Appraisal Scale: A cross-sectional survey.

AIMS: To assess barriers to insulin therapy among people with type 2 diabetes after adapting the Insulin Treatment Appraisal Scale (ITAS) to the South African context. METHODS: A panel of experts reviewed the original ITAS for clarity and relevance to the South African context. The ITAS was administered to 253 adults with type 2 diabetes attending diabetes outpatient clinics in the Tshwane Metropolitan Municipality. Internal consistency (Cronbach's alpha) was tested and construct validity was examined using exploratory factor analysis (EFA). PIR was appraised in insulin users and non-users. RESULTS: The EFA revealed that the adapted ITAS had a two-factor structure, similar to the original scale, with acceptable internal consistency (α = 0.85). Insulin-using participants had significantly less negative attitudes to insulin therapy than non-users (40.7 ± 7.1 vs. 51.5 ± 11.2, p < 0.001). Compared to participants who used insulin, participants who did not use insulin were afraid of injecting themselves with a needle (71% vs. 11%, p < 0.001) and saw insulin treatment as a sign of worsening diabetes (63% vs. 29%, p < 0.001). CONCLUSIONS: Consistent with previous studies, participants who were not using insulin had more negative beliefs and attitudes towards insulin treatment than those who were already using insulin. South African clinicians should use the ITAS to assess positive and negative perceptions regarding insulin therapy in both insulin-naïve and insulin-treated people, to evaluate interventions to reduce PIR and improve treatment outcomes.

Designing an integrated, nurse-driven and home-based digital intervention to improve insulin management in under-resourced settings.

BACKGROUND: In South Africa, initiating insulin for people with type 2 diabetes and subsequent titration is a major challenge for the resource-constrained healthcare system. Inadequate support systems in primary care, including not being able to access blood glucose monitors and test strips for self-monitoring of blood glucose, results in patients with type 2 diabetes being referred to higher levels of care. In primary care, initiation of insulin may be delayed due to a shortage of healthcare workers. The delayed initiation of insulin is also exacerbated by the reported resistance of both healthcare providers and people with type 2 diabetes to start insulin. In South Africa, telehealth provides an opportunity to overcome these challenges and manage insulin therapy in primary care. METHODS: We describe the development of a digital health intervention including the framework used, the theoretical approach and subsequent implementation strategies. RESULTS: This intervention is an innovative, nurse-driven and app-enabled intervention called 'the Tshwane Insulin Project intervention'. The Tshwane Insulin Project intervention was designed and evaluated using the framework recommended by the Medical Research Council for complex interventions. The Tshwane Insulin Project intervention was developed in four sequential phases: planning, design, implementation and evaluation. The Tshwane Insulin Project intervention followed the Integrated Chronic Disease Management framework to facilitate implementation and acceptability. The Tshwane Insulin Project comprises a facility-level intervention, where nurses evaluate patients and initiate insulin, an individual-level intervention where community healthcare workers visit patients at their homes to follow-up and provide educational information, while using telehealth to enable physician-directed insulin titration if needed, and a community-level intervention aimed at empowering community healthcare workers to support people living with diabetes and raise awareness of diabetes. CONCLUSION: The technological advancements in digital health and telemedicine present an opportunity to improve diabetes care in resource-limited countries. This work can inform those intending to develop and implement complex interventions in primary healthcare in developing countries.

Home-based pulmonary rehabilitation early after hospitalisation in COPD (early HomeBase): protocol for a randomised controlled trial.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterised by exacerbations of respiratory disease, frequently requiring hospital admission. Pulmonary rehabilitation can reduce the likelihood of future hospitalisation, but programme uptake is poor. This study aims to compare hospital readmission rates, clinical outcomes and costs between people with COPD who undertake a home-based programme of pulmonary rehabilitation commenced early (within 2 weeks) of hospital discharge with usual care. METHODS: A multisite randomised controlled trial, powered for superiority, will be conducted in Australia. Eligible patients admitted to one of the participating sites for an exacerbation of COPD will be invited to participate. Participants will be randomised 1:1. Intervention group participants will undertake an 8-week programme of home-based pulmonary rehabilitation commencing within 2 weeks of hospital discharge. Control group participants will receive usual care and a weekly phone call for attention control. Outcomes will be measured by a blinded assessor at baseline, after the intervention (week 9-10 posthospital discharge), and at 12 months follow-up. The primary outcome is hospital readmission at 12 months follow-up. ETHICS AND DISSEMINATION: Human Research Ethics approval for all sites provided by Alfred Health (Project 51216). Findings will be published in peer-reviewed journals, conferences and lay publications. TRIAL REGISTRATION NUMBER: ACTRN12619001122145.

Inter-rater agreement of scores to assess quality of care in public sector primary health care facilities - A pattern of performance.

PURPOSE: To determine if the scores obtained from the Ideal Clinic Assessment Tool (ICAT) used to assess the quality of care in public Primary Health Care facilities in South Africa showed inter-rater agreement between self-assessments, district peer reviews and cross-district peer reviews. The ICAT scores obtained in the three types of reviews were paired as follows: self-assessments/district peer reviews, self-assessment/cross-district peer reviews and district/cross-district peer reviews. The global scores and averages of the Vital elements for the three paired reviews for 587 facilities across the country were compared using Bland-Altman plots. RESULTS: The Bland-Altman plots showed no inter-rater agreement between the global scores and averages of the Vital elements for the facilities in any of the paired reviews (n = 1 761 reviews). Similarly, there was no inter-rater agreement between the global scores of the three paired reviews in any of the nine provinces in the country. CONCLUSION: There is still a need to continue to conduct both district and cross-district reviews despite the substantial cost of doing so. Further studies are required to determine what factors contributed to the disagreement in scores between the different types of reviews despite the preparatory training of reviewers.

Attitudes and beliefs of South African primary healthcare practitioners on initiating insulin in people with type 2 diabetes: Findings from the Tshwane Insulin Project (TIP).

AIMS: To investigate the attitudes and beliefs of primary healthcare practitioners (HCPs) towards initiating insulin therapy for people with type 2 diabetes (T2D) in South Africa. METHODS: A cross-sectional survey was conducted amongst HCPs from 23 clinics. The nurses' questionnaire was administered by research nurses while doctors completed an online version about their attitudes, beliefs and perceived barriers to initiating insulin. RESULTS: Of the 73 HCPs surveyed, 68% were nurses and 84% were women. Only 24% of HCPs believed that most patients would eventually need to initiate insulin regardless of their adherence to treatment regimens and 86% preferred to delay insulin therapy. Doctors were reluctant to initiate insulin, citing patient-related reasons such as low socio-economic level (41%), inability to refrigerate insulin (77%) and inability to self-monitor blood glucose (55%). Doctors mentioned that patient behaviour including not adhering to treatment regimen and appointments (91%) and reluctance to start insulin therapy (82%) influenced their prescription practices. Doctors mentioned that health system factors, including the pressure to see patients quickly (68%) and lack of continuity of care (64%) were barriers to initiating insulin. CONCLUSIONS: Optimising insulin therapy in primary care requires health system changes including promoting person-centred care and continuing training for HCPs.

Racial disparities in COVID-19 outcomes exist despite comparable Elixhauser comorbidity indices between Blacks, Hispanics, Native Americans, and Whites.

Factors contributing to racial inequities in outcomes from coronavirus disease 2019 (COVID-19) remain poorly understood. We compared by race the risk of 4 COVID-19 health outcomes--maximum length of hospital stay (LOS), invasive ventilation, hospitalization exceeding 24 h, and death--stratified by Elixhauser comorbidity index (ECI) ranking. Outcomes and ECI scores were constructed from retrospective data obtained from the Cerner COVID-19 De-Identified Data cohort. We hypothesized that racial disparities in COVID-19 outcomes would exist despite comparable ECI scores among non-Hispanic (NH) Blacks, Hispanics, American Indians/Alaska Natives (AI/ANs), and NH Whites. Compared with NH Whites, NH Blacks had longer hospital LOS, higher rates of ventilator dependence, and a higher mortality rate; AI/ANs, higher odds of hospitalization for ECI = 0 but lower for ECI ≥ 5, longer LOS for ECI = 0, a higher risk of death across all ECI categories except ECI ≥ 5, and higher odds of ventilator dependence; Hispanics, a lower risk of death across all ECI categories except ECI = 0, lower odds of hospitalization, shorter LOS for ECI ≥ 5, and higher odds of ventilator dependence for ECI = 0 but lower for ECI = 1-4. Our findings contest arguments that higher comorbidity levels explain elevated COVID-19 death rates among NH Blacks and AI/ANs compared with Hispanics and NH Whites.

Suboptimal control for patients with type 2 diabetes in the Central Chronic Medicine Dispensing programme in South Africa.

BACKGROUND: In South Africa, the Central Chronic Medicine Dispensing and Distribution (CCMDD) programme allows stable patients with non-communicable diseases, including type 2 diabetes mellitus (T2DM), to collect their medication from a pick-up location near their home, thus avoiding long waiting times and travel expenses. The CCMDD programme aims at improving patient retention and adherence through better access to medicines, resulting in better health outcomes. AIM: We assessed whether patients with T2DM enrolled in CCMDD achieved the recommended targets for glycaemic, blood pressure (BP) and lipid control. SETTING: City of Tshwane, South Africa. METHODS: We reviewed the records of 198 T2DM patients enrolled in CCMDD and assessed their control of haemoglobin A1c (HbA1c), BP and lipids. RESULTS: Most of the records reviewed belonged to women (64.7%), African (89.9%), hypertensive (82.7%) and to patients exclusively on oral antidiabetic agents (98.5%). Patients were, on average, 57.7 (s.d. = 12.1) years old and had participated in the CCMDD programme for, on average, 2 years. The mean HbA1c was 8% (s.d. = 2). Glycaemic control was achieved by only 29.2% of patients, and 49% of patients had HbA1c between 7% and 9%. Ninety-three patients (66%) had achieved the total cholesterol target, 57.4% achieved BP targets and 6.9% had achieved the low-density lipoprotein cholesterol target. CONCLUSION: A small group of patients achieved the targets for glycaemic, BP and lipid control. Despite improved accessibility to medication, the CCMDD is not synonymous of improved clinical outcomes. Future research should ascertain the factors associated with suboptimal control for these patients.

Application of the Modified Incremental Step Test for Pulmonary Rehabilitation.

OBJECTIVE: A Modified Incremental Step Test (MIST) performed in the home may facilitate entirely home-based pulmonary rehabilitation programs. The aims of this study were to investigate the reliability and responsiveness, and the utility of the MIST for exercise prescription in people with stable chronic lung disease. METHODS: The MIST was undertaken at the center and home in random order, before and after pulmonary rehabilitation, with 2 tests at each time point. Reliability was assessed using intraclass correlation coefficient. Responsiveness was evaluated as effect size. The minimal important difference was appraised using distribution and anchor-based methods. In a substudy, physiological responses to MIST were measured by a portable metabolic system, followed by a constant step rate test at 60% of peak oxygen uptake (VO2peak), to evaluate utility for exercise prescription. RESULTS: Forty-six participants were recruited (29% of eligible candidates). There was excellent reliability for number of steps recorded in home- and center-based settings (intraclass correlation coefficient = 0.954, 95% CI = 0.915-0.976). A small-moderate effect size was demonstrated following pulmonary rehabilitation (0.34), and the minimal detectable change was 7 steps. All participants in the substudy achieved 60% of VO2peak and achieved steady state by the fourth minute, with 60% of VO2peak corresponding to a mean 37% (95% CI = 29-44) of the MIST final level. CONCLUSIONS: The MIST is reliable and responsive to pulmonary rehabilitation in people with stable chronic respiratory disease. It provides new opportunities to assess exercise capacity, prescribe exercise training, and reassess exercise program outcomes in environments where established field walking tests are not feasible. IMPACT: Pulmonary rehabilitation is a highly effective treatment that is underutilized worldwide. Home-based pulmonary rehabilitation may improve access for patients and deliver equivalent clinical outcomes but is limited by the availability of a robust exercise test that can be used at home to assess exercise capacity and prescribe training intensity. This study tested the clinimetric properties of the MIST and demonstrated a new way to assess exercise capacity, prescribe exercise training of an appropriate intensity, and reassess exercise capacity in environments where established field walking tests are not feasible.

The clinical outcomes of patients with diabetes and hypertension in a peri-urban area, Johannesburg, South Africa.

AIM: To describe the clinical outcomes of patients with type 2 diabetes (DM2) and hypertension (HT) who received treatment and care at a specialized primary healthcare facility. METHODS: A cross-sectional study was conducted and data retrieved from 349 patient's records. The clinical outcomes were linked to individual risk factors and demographic profiles. Patients with HT who had at least four blood pressure (BP) measurements and patients with DM2 who had at least two HbA1c measurements in a 12-month period were included. RESULTS: More females had controlled HT than males. There was no sex difference observed for the control of DM2. Patients with HT visited the clinic for a median period of 96 days (IQR 35-257). Among 59.1% (n = 159) patients who achieved at least one controlled BP measurement, 64.2% (n = 102) had a controlled BP at the last visit. Patients with DM2 visited the clinic for a median period of 851 days (IQR 449.5-1254). From a total of 34 patients (43.5%) who achieved at least one controlled HbA1c measurement, 55.9% (n = 19) had a controlled HbA1c at the last visit. CONCLUSION: Despite the difference in patient profiles, more than half of the patients who received specialised DM2 and HT care managed to achieve BP and HbA1c control.

Willingness of people with Type 2 diabetes to start insulin therapy: Evidence from the South African Tshwane Insulin Project (TIP).

AIMS: To determine factors associated with 'hypothetical willingness' to start insulin among people with Type 2 diabetes (T2DM). METHODS: A quantitative cross-sectional study with insulin-naïve T2DM patients at 23 primary care facilities in the Tshwane Metropolitan Municipality. Data collected included demographic and clinical data, willingness to start insulin, attitudes and barriers to insulin therapy. Factors associated with unwillingness to start insulin therapy were explored using a multivariable logistic regression model. RESULTS: Of 468 T2DM study patients (mean age 57.2, SD = 11.3 years), more than half (51.9%) expressed unwillingness to starting insulin therapy. Unwillingness was associated with negative attitudes (OR = 1.32, 95% CI = 1.12-1.55, p = 0.001) and reluctance (OR = 1.41, 95% CI = 1.27-1.57, p < 0.001) rather than age, sex, education or diabetes duration. The strongest reasons for patient unwillingness were injection anxieties, fear of needles, insufficient knowledge of insulin, feeling unable to cope with insulin and concerns about out-of-pocket costs. CONCLUSIONS: The prospect of insulin therapy disturbs patients' sense of self and their psychological wellbeing. The high prevalence of psychological insulin resistance among these T2DM patients needs to be addressed for effective diabetes management.

Racial Disparities in COVID-19 Mortality Among Essential Workers in the United States.

Racial disparities are apparent in the impact of coronavirus disease 2019 (COVID-19) in the United States, yet the factors contributing to racial inequities in COVID-19 mortality remain controversial. To better understand these factors, we investigated racial disparities in COVID-19 mortality among America's essential workers. Data from the American Community Survey and Current Population Survey was used to examine the correlation between the prevalence of COVID-19 deaths and occupational differences across racial/ethnic groups and states. COVID-19 mortality was higher among non-Hispanic (NH) Blacks compared with NH Whites, due to more NH Blacks holding essential-worker positions. Vulnerability to coronavirus exposure was increased among NH Blacks, who disproportionately occupied the top nine essential occupations. As COVID-19 death rates continue to rise, existing structural inequalities continue to shape racial disparities in this pandemic. Policies mandating the disaggregation of state-level data by race/ethnicity are vital to ensure equitable and evidence-based response and recovery efforts.

Compression Therapy to Prevent Recurrent Cellulitis of the Leg.

BACKGROUND: Chronic edema of the leg is a risk factor for cellulitis. Daily use of compression garments on the leg has been recommended to prevent the recurrence of cellulitis, but there is limited evidence from trials regarding its effectiveness. METHODS: In this single-center, randomized, nonblinded trial, we assigned participants with chronic edema of the leg and recurrent cellulitis, in a 1:1 ratio, to receive leg compression therapy plus education on cellulitis prevention (compression group) or education alone (control group). Follow-up occurred every 6 months for up to 3 years or until 45 episodes of cellulitis had occurred in the trial. The primary outcome was the recurrence of cellulitis. Participants in the control group who had an episode of cellulitis crossed over to the compression group. Secondary outcomes included cellulitis-related hospital admission and quality-of-life assessments. RESULTS: A total of 183 patients were screened, and 84 were enrolled; 41 participants were assigned to the compression group, and 43 to the control group. At the time of a planned interim analysis, when 23 episodes of cellulitis had occurred, 6 participants (15%) in the compression group and 17 (40%) in the control group had had an episode of cellulitis (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.59; P = 0.002; relative risk [post hoc analysis], 0.37; 95% CI, 0.16 to 0.84; P = 0.02), and the trial was stopped for efficacy. A total of 3 participants (7%) in the compression group and 6 (14%) in the control group were hospitalized for cellulitis (hazard ratio, 0.38; 95% CI, 0.09 to 1.59). Most quality-of-life outcomes did not differ between the two groups. No adverse events occurred during the trial. CONCLUSIONS: In this small, single-center, nonblinded trial involving patients with chronic edema of the leg and cellulitis, compression therapy resulted in a lower incidence of recurrence of cellulitis than conservative treatment. (Funded by Calvary Public Hospital Bruce; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000412336.).

Review and analysis of the potential for glyphosate to interact with the estrogen, androgen and thyroid pathways.

Glyphosate was recently evaluated for its potential to interact with the estrogen, androgen and thyroid (EAT) hormone pathways, including steroidogenesis, under the United States Environmental Protection Agency's (USEPA) Endocrine Disruptor Screening Program (EDSP), then by Germany, the rapporteur Member State who led the European Annex 1 renewal for glyphosate, and then by the European Food Protection Agency (EFSA) also as part of the Annex 1 renewal for glyphosate. Under the EDSP, 11 Tier 1 assays were run following the USEPA's validated 890-series test guidelines and included five in vitro and six in vivo assays to evaluate the EAT pathways. Steroidogenesis was evaluated as part of the estrogen and androgen pathways. An up-to-date critical review has been conducted that considered results from the EDSP Tier 1 battery, guideline regulatory studies and an in-depth analysis of the literature studies that informed an endocrine assessment. A strength of this evaluation was that it included data across multiple levels of biological organization, and mammalian and nonmammalian test systems. There was strong agreement across the in vitro and in vivo Tier 1 battery, guideline studies and relevant literature studies, demonstrating that glyphosate does not interact with EAT pathways including steroidogenesis. Based on an analysis of the comprehensive toxicology database for glyphosate and the literature, this review has concluded that glyphosate does not have endocrine-disrupting properties through estrogen, androgen, thyroid and steroidogenic modes of action. © 2020 Society of Chemical Industry.