Occupational exposures and sarcoidosis: a rapid review of the evidence.

BACKGROUND: Sarcoidosis is a rare, multisystem, inflammatory condition associated with the formation of granulomas. Diagnosis can be challenging because of non-specific symptoms complicating epidemiological investigations of its aetiology. Despite research efforts, a review of the current state of the evidence is needed. AIMS: To assess the evidence for an association between occupational exposures and the development of sarcoidosis. To determine if workers in any occupation are at a greater risk of developing sarcoidosis. METHODS: This rapid review follows the methodology suggested by the World Health Organization. Two electronic databases were systematically searched until April 2022. The methodological quality of the studies was critically appraised, and a best-evidence approach was used to synthesize the results. RESULTS: Titles and abstracts of 2916 articles were screened, with 67 full-text articles reviewed for eligibility. Among the 13 studies eligible for this review, none were of high quality (i.e. low risk of bias). Six studies exploring the association between sarcoidosis and a range of occupations and exposures, and one previous systematic review were of low quality reporting inconsistent findings. Six studies examined the risk of sarcoidosis associated with occupational silica exposure, two of which were of acceptable quality. Overall, the study methodologies and results were inadequate to support causal relationships. CONCLUSIONS: There is limited evidence of acceptable methodological quality to assess the risk of sarcoidosis associated with occupational exposures. There is a growing body of research examining occupational exposure to silica and sarcoidosis. Additional high-quality confirmatory research is needed.

The contribution of personal audio system use and commuting by bus on daily noise dose.

BACKGROUND: For many young people, exposure to music from personal audio system use may represent a significant component of daily noise dose. Moreover, there is increasing concern for the hearing of those who listen at high volumes. The purpose of this study was to determine the noise levels experienced on commuter buses, and to investigate how these impact on the volume-setting behavior of young adult personal audio system users. METHODS: A questionnaire was used to probe transport use, personal audio system-listening behaviors and the extent of understanding about noise-induced hearing loss. The influence of bus noise on volume-setting behavior was determined by measuring, in a lab setting, the sound-level preferences of participants when listening to their favorite song, a generic song, or a podcast in the absence and presence of various levels of bus noise, simulated using output-adjusted recordings made of bus noise. Statistical analysis was conducted using analysis of variance. RESULTS: While the bus noise itself was below 85 dB Leq, as the sound level of the buses increased, so did the percentage of commuters who were found to exceed the equivalent of 8 hours of exposure at 85 dB Leq. IMPLICATIONS: Investment in buses with lower noise levels or the use of noise-canceling or noise-occluding headphones would help to reduce the likelihood of noise-induced hearing loss for bus commuters.

Abnormal platelet activity in dogs and cats - impact and measurement.

Abnormal platelet activity can either lead to bleeding tendencies or inappropriate thrombus formation and can occur secondarily to a wide variety of disease processes, with a range of clinical consequences and severity. This article will discuss the pathophysiology of platelet function abnormalities and consider a logical diagnostic approach applicable to veterinary practice. Recent advances in platelet function testing will then be discussed, with regards to detection of platelet dysfunction and tailoring of pharmacological manipulation. Although many of these tests are still confined to research or academic institutions, techniques for indirectly assessing platelet function are starting to become more widely available. Although we still require further research to develop guidelines for the use of these tests in clinical decision-making, the recent advances in this field are an exciting step forward in being able to detect and manage platelet dysfunction in both primary care and referral practice.

Enhancing bowel screening: Preventing colorectal cancer by flexible sigmoidoscopy in New Zealand.

OBJECTIVES: The prevention of colorectal cancer (CRC) attainable from introducing once-in-a-lifetime flexible sigmoidoscopy (FSIG) screening was assessed. STUDY DESIGN: This is a review of relevant available information for the assessment of the impact and resource demands of FSIG in New Zealand. METHODS: The reduction in bowel cancer incidence achievable by one-off FSIG screening from 50 to 59 years of age, an age group for which bowel screening is not currently offered, was reviewed. The prevention of CRC attainable from an offer of screening at 55 years of age in New Zealand was also estimated. The number and cost of the FSIG screening procedures required and referrals for colonoscopies and the savings in treatment were calculated. RESULTS: Annually, about 27,500 FSIG screening procedures would be required if 50% of those turning 55 years of age accepted an offer of once-in-a-lifetime FSIG screening. This would result in three-four-fold fewer people being referred for colonoscopy than in the national 2-yearly faecal immunochemical test (FIT) screening programme and subsequently reduce demand for colonoscopy from a false-positive FIT. The number of CRC cases prevented would increase over 17 years to more than 300 per year by 2033. After 10-15 years of screening, the annual savings in health service costs, primarily from CRC prevented, were sufficient to completely fund the FSIG screening. CONCLUSIONS: Inclusion of FSIG screening in the national bowel screening programme would significantly reduce both the incidence and mortality of CRC in New Zealand, reduce the colonoscopy demand of current bowel screening and reduce long-term health service costs.

Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

Secukinumab significantly reduces psoriasis-related work impairment and indirect costs compared with ustekinumab and etanercept in the United Kingdom.

BACKGROUND: Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. OBJECTIVE: To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). METHODS: This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (i) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (ii) weekly/annual work productivity loss by PASI response level; (iii) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (iv) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different time points and with patient cohorts, including FIXTURE. RESULTS: In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI < 50: 22.8%/7.60 h; PASI 50-74: 13.3%/4.45 h; PASI 75-89: 6.4%/2.14 h; PASI ≥ 90: 4.9%/1.65 h. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P = 0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρ<0.0001). Average annual indirect cost savings with secukinumab were £355 vs. ustekinumab and £1061 versus etanercept. Results at 52 weeks were similar. CONCLUSIONS: Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the United Kingdom.

Angioedema in chronic spontaneous urticaria is underdiagnosed and has a substantial impact: Analyses from ASSURE-CSU.

BACKGROUND: ASSURE-CSU revealed differences in physician and patient reporting of angioedema. This post hoc analysis was conducted to evaluate the actual rate of angioedema in the study population and explore differences between patients with and without angioedema. METHODS: This international observational study assessed 673 patients with inadequately controlled chronic spontaneous urticaria (CSU). Physicians abstracted angioedema data from medical records, which were compared with patient-reported data. Patients in the Yes-angioedema category had angioedema reported in the medical record and a patient-reported source. For those in the No-angioedema category, angioedema was reported in neither the medical record nor a patient-reported source. Those in the Misaligned category had angioedema reported in only one source. Statistical comparisons between Yes-angioedema and No-angioedema categories were conducted for measures of CSU activity, health-related quality of life (HRQoL), productivity and healthcare resource utilization (HCRU). Regression analyses explored the relationship between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for important covariates. RESULTS: Among evaluable patients, 259 (40.3%), 173 (26.9%) and 211 (32.8%) were in the Yes-angioedema, No-angioedema and Misaligned category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU was greater for Yes-angioedema patients than No-angioedema patients. After covariate adjustment, mean DLQI score was significantly higher (indicating worse HRQoL) for patients with angioedema versus no angioedema (9.88 vs 7.27, P < .001). The Misaligned category had similar results with Yes-angioedema on all outcomes. CONCLUSIONS: Angioedema in CSU seems to be under-reported but has significant negative impacts on HRQoL, daily activities, HCRU and work compared with no angioedema.

The burden of chronic spontaneous urticaria is substantial: Real-world evidence from ASSURE-CSU.

BACKGROUND: Chronic spontaneous urticaria (CSU) can be debilitating, difficult to treat, and frustrating for patients and physicians. Real-world evidence for the burden of CSU is limited. The objective of this study was to document disease duration, treatment history, and disease activity, as well as impact on health-related quality of life (HRQoL) and work among patients with inadequately controlled CSU, and to describe its humanistic, societal, and economic burden. METHODS: This international observational study assessed a cohort of 673 adult patients with CSU whose symptoms persisted for ≥12 months despite treatment. Demographics, disease characteristics, and healthcare resource use in the previous 12 months were collected from medical records. Patient-reported data on urticaria and angioedema symptoms, HRQoL, and work productivity and activity impairment were collected from a survey and a diary. RESULTS: Almost 50% of patients had moderate-to-severe disease activity as reported by Urticaria Activity Score. Mean (SD) Dermatology Life Quality Index and Chronic Urticaria Quality of Life Questionnaire scores were 9.1 (6.62) and 33.6 (20.99), respectively. Chronic spontaneous urticaria markedly interfered with sleep and daily activities. Angioedema in the previous 12 months was reported by 66% of enrolled patients and significantly affected HRQoL. More than 20% of patients reported ≥1 hour per week of missed work; productivity impairment was 27%. These effects increased with increasing disease activity. Significant healthcare resources and costs were incurred to treat CSU. CONCLUSIONS: Chronic spontaneous urticaria has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater HRQoL impairments.

Analysis of disease activity categories in chronic spontaneous/idiopathic urticaria.

BACKGROUND: Measurement of disease activity guides treatment of chronic spontaneous urticaria (CSU). A weekly Urticaria Activity Score - here, the average of twice-daily patient assessment of itch and hives scores summed over 1 week (UAS7TD ) - measures severity from 0 to 42. Insufficient evidence exists on whether disease activity states, defined by categorical UAS7TD scores, correlate with other patient-reported outcomes and treatment response. OBJECTIVES: To evaluate and compare categorical UAS7TD scores with selected measures of disease-related quality of life and impact. METHODS: Data from three randomized clinical trials of omalizumab in CSU were pooled. Continuous UAS7TD scores were categorized into five disease activity states: urticaria-free, well-controlled, mild, moderate and severe urticaria. Total scores from the Dermatology Life Quality Index; the Chronic Urticaria Quality of Life questionnaire; and questions on sleep and daily activity interference, presence of angioedema and diphenhydramine use were compared within categorized UAS7TD disease-state scores, using anova for analysis at different time points and mixed-effects regressions for analysis of all data pooled. RESULTS: Pooled analyses showed that categorical UAS7TD disease states accurately predicted differences among treated patients with CSU with different levels of disease activity. A consistent pattern existed between categories, with higher-activity disease states associated with significantly higher impact and an increase in angioedema frequency. Results at different treatment time points were consistent. CONCLUSIONS: Categorical UAS7TD disease states can discriminate between measures when considering the impact of urticaria activity. Using five categorical disease states could simplify clinical assessment and monitoring of treatment efficacy.

Secukinumab treatment of plaque psoriasis shows early improvement in DLQI response - results of a phase II regimen-finding trial.

BACKGROUND: The social stigma and chronicity of psoriasis significantly affect health-related quality of life (HRQoL). OBJECTIVE: We examined the effect of three regimens of secukinumab on HRQoL in moderate to severe psoriasis patients. METHODS: Twelve-week data from a phase II, randomized, double-blind, placebo-controlled, regimen-finding study evaluated HRQoL, measured by the Dermatology Life Quality Index (DLQI). Secukinumab or placebo was administered subcutaneously in three treatment regimens: single (baseline only), monthly (baseline, weeks 4, 8) and early (baseline, weeks 1, 2, 4). Differences among regimens were assessed with logistic regression models and Fisher's exact test. RESULTS: Patients (n = 404) were randomized to single (baseline) treatment regimen, n = 66; monthly, (baseline, weeks 4 and 8), n = 138; early, (baseline, weeks 1, 2, 4), n = 133; and placebo, n = 67. DLQI response was significantly higher in early, monthly and single regimens than in placebo regimen (40.8%, 33.6% and 13.1% vs. 1.6%, respectively; P < 0.001 for all). CONCLUSION: Moderate to severe psoriasis patients receiving monthly and early treatment with secukinumab demonstrated improved HRQoL compared with placebo.

Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort.

BACKGROUND: Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria. METHODS: Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge. RESULTS: Across Europe, 12 049 children were enrolled, and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA. CONCLUSIONS: This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon.

Responsible corporate change: detecting and managing employee stress.

BACKGROUND: All 120 health and safety inspectors employed by the New Zealand regulatory agency had their jobs disestablished during a restructuring process and were required to undergo an assessment process with tight time frames. AIMS: To report on psychological morbidity during the transition to change. METHODS: The Hospital Anxiety and Depression Scale (HADS) questionnaire was emailed to all 120 current inspectors to measure levels of anxiety (HAD-A) and depression (HAD-D). A score of <7 is in the normal range, scores of between 8 and 10 are suggestive of an anxiety (HADS-A) or mood (HADS-D) disorder and a score of >11 is indicative of a clinical disorder. RESULTS: Replies were received from 36% (43) of the inspectors. Of the 40 usable responses, 47% (19) and 55% (22), respectively, had HAD-A and HAD-D scores greater than the case cut-off. Only 28% (11) and 15% (6), respectively, had scores that would be considered normal. CONCLUSIONS: The high scores evident in this sample are comparable to those found in patients with serious psychopathology. Change managers should recognize that the onus for primary prevention lies with the organization, in this case designing an assessment process that takes place over a reasonable time frame. They should also realize the requirement for the active monitoring of stress.

Riot control agents: the tear gases CN, CS and OC-a medical review.

INTRODUCTION: 2-Chloroacetophenone (CN), o-chlorobenzylidene malonitrile (CS) and oleoresin capsicum (OC) are common riot control agents. While serious systemic effects are uncommon, exposure to high concentrations may lead to severe complications and even death. The aim of this narrative review is to summarise all main aspects of the riot control agents CN, CS and OC toxicology, including mechanisms of toxicity, clinical features and management. METHODS: OVID MEDLINE and ISI Web of Science were searched for terms associated with CN, CS and OC toxicity in humans and those describing the mechanism of action, clinical features and treatment protocols. RESULTS: CN, CS and OC are effective lacrimating agents; evidence for toxicity, as measured by the threshold for irritation, is greatest for CN, followed by CS and OC. Typically, ocular and respiratory tract irritation occurs within 20-60 s of exposure. Ocular effects involve blepharospasm, photophobia, conjunctivitis and periorbital oedema. Following inhalation, effects may include a stinging or burning sensation in the nose, tight chest, sore throat, coughing, dyspnoea and difficulty breathing. Dermal outcomes are variable, more severe for CN and include dermal irritation, bulla formation and subcutaneous oedema. Removal from the contaminated area and fresh air is a priority. There is no antidote; treatment consists of thorough decontamination and symptom-directed supportive care. Ocular exposure requires thorough eye decontamination, an eye exam and appropriate pain management. Monitoring and support of respiratory function is important in patients with significant respiratory symptoms. Standard treatment protocols may be required with patients with pre-existing respiratory conditions. Dermal exposures may require systemic steroids for patients who develop delayed contact dermatitis. CONCLUSIONS: CN, CS and OC are effective riot control agents. In the majority of exposures, significant clinical effects are not anticipated. The irritant effects can be minimised both by rapid evacuation from sites of exposure, decontamination and appropriate supportive care.

Musculoskeletal disorders among nurses compared with two other occupational groups.

BACKGROUND: There is a high incidence of low back pain (LBP) among nurses. However, few longitudinal studies have investigated musculoskeletal disorders (MSDs) at other anatomical sites in nurses. AIMS: To describe the cumulative incidence and persistence/recurrence of MSDs of the low back, neck, shoulder, elbow, wrist/hand and knee among New Zealand nurses, to investigate the impact of MSDs on work and functional tasks and to compare findings for nurses with those in postal workers and office workers. METHODS: Participants completed a postal survey at baseline and again 1 year later. Information was collected about MSDs in the previous 1 month and 12 months and about the ability to attend work, undertake work duties and perform functional tasks. RESULTS: Among nurses, the low back was the site with the highest cumulative incidence and highest prevalence of persistent/recurrent, work-disabling and functional-task-disabling pain. Work-disabling LBP was more prevalent among nurses and postal workers than office workers (P < 0.001). Nurses had a substantial prevalence of work-disabling shoulder pain (10%) and functional-task-disabling knee (19%) and wrist/hand pain (16%). With the exception of the elbow, each occupational group had a high prevalence of persistent/recurrent MSDs at all anatomical sites. CONCLUSIONS: LBP continues to have a substantial impact among nurses. Other less commonly considered MSDs, such as shoulder, wrist/hand and knee pain, also made work or functional tasks difficult, suggesting that primary and secondary prevention efforts should consider MSDs at other anatomical sites as well as the low back.

Dietary habits and supplement use in relation to national pregnancy recommendations: data from the EuroPrevall birth cohort.

Assessing maternal dietary habits across Europe during pregnancy in relation to their national pregnancy recommendations. A collaborative, multi-centre, birth cohort study in nine European countries was conducted as part of European Union funded EuroPrevall project. Standardised baseline questionnaire data included details of food intake, nutritional supplement use, exposure to cigarette smoke during pregnancy and socio-demographic data. Pregnancy recommendations were collected from all nine countries from the appropriate national organisations. The most commonly taken supplement in pregnancy was folic acid (55.6 % Lithuania-97.8 % Spain) and was favoured by older, well-educated mothers. Vitamin D supplementation across the cohort was very poor (0.3 % Spain-5.1 % Lithuania). There were significant differences in foods consumed in different countries during pregnancy e.g. only 2.7 % Dutch mothers avoided eating peanut, while 44.4 % of British mothers avoided it. Some countries have minimal pregnancy recommendations i.e. Lithuania, Poland and Spain while others have similar, very specific recommendations i.e. UK, the Netherlands, Iceland, Greece. Allergy specific recommendations were associated with food avoidance during pregnancy [relative rate (RR) 1.18 95 % CI 0.02-1.37]. Nutritional supplement recommendations were also associated with avoidance (RR 1.08, 1.00-1.16). Maternal dietary habits and the use of dietary supplements during pregnancy vary significantly across Europe and in some instances may be influenced by national recommendations.

Noise exposure of workers and the use of hearing protection equipment in New Zealand.

Hearing loss from occupational noise exposure is a significant occupational health problem, requiring effective health and safety strategies. Essential to this is an understanding of the noise exposure of workers and the use of hearing protection equipment (HPE). This study reports on data collected in New Zealand. Visits were made to companies in each economic sector. Personal dosimetry was used to assess individual noise exposure of 529 workers. Workers were also interviewed about their use of HPE. Overall, 40.4% of production workers had a daily noise exposure greater than 1 Pa(2)h, exceeding the New Zealand National Standard for occupational noise exposure without HPE. Of these, 88.5% reported to use HPE when working in noise; however, some observations suggested that workers do not consistently use the devices. These data add to the overall picture of noise exposure of workers in New Zealand and are especially useful in areas where data did not previously exist or were difficult to access.

Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary.

Little is known about the involvement of microRNAs (miRNAs) in the follicular-luteal transition. The aim of this study was to identify genome-wide changes in miRNAs associated with follicular differentiation in sheep. miRNA libraries were produced from samples collected at defined stages of the ovine oestrous cycle and representing healthy growing follicles, (diameter, 4.0-5.5  mm), pre-ovulatory follicles (6.0-7.0  mm), early corpora lutea (day 3 post-oestrus) and late corpora lutea (day 9). A total of 189 miRNAs reported in sheep or other species and an additional 23 novel miRNAs were identified by sequencing these libraries. miR-21, miR-125b, let-7a and let-7b were the most abundant miRNAs overall, accounting for 40% of all miRNAs sequenced. Examination of changes in cloning frequencies across development identified nine different miRNAs whose expression decreased in association with the follicular-luteal transition and eight miRNAs whose expression increased during this transition. Expression profiles were confirmed by northern analyses, and experimentally validated targets were identified using miRTarBase. A majority of the 29 targets identified represented genes known to be actively involved in regulating follicular differentiation in vivo. Finally, luteinisation of follicular cells in vitro resulted in changes in miRNA levels that were consistent with those identified in vivo, and these changes were temporally associated with changes in the levels of putative miRNA targets in granulosa cells. In conclusion, this is the first study to characterise genome-wide miRNA profiles during different stages of follicle and luteal development. Our data identify a subset of miRNAs that are potentially important regulators of the follicular-luteal transition.