Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults.

BACKGROUND: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent. METHODS: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D3 (2000 IU per day), n-3 fatty acids (1 g per day), or both would prevent cancer and cardiovascular disease in men 50 years of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual questionnaires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses. RESULTS: Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P = 0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P = 0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial. CONCLUSIONS: Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.).

Hepatobiliary circulation and dominant urinary excretion of homogentisic acid in a mouse model of alkaptonuria.

Altered activity of specific enzymes in phenylalanine-tyrosine (phe-tyr) metabolism results in incomplete breakdown of various metabolite substrates in this pathway. Increased biofluid concentration and tissue accumulation of the phe-tyr pathway metabolite homogentisic acid (HGA) is central to pathophysiology in the inherited disorder alkaptonuria (AKU). Accumulation of metabolites upstream of HGA, including tyrosine, occurs in patients on nitisinone, a licenced drug for AKU and hereditary tyrosinaemia type 1, which inhibits the enzyme responsible for HGA production. The aim of this study was to investigate the phe-tyr metabolite content of key biofluids and tissues in AKU mice on and off nitisinone to gain new insights into the biodistribution of metabolites in these altered metabolic states. The data show for the first time that HGA is present in bile in AKU (mean [±SD] = 1003[±410] µmol/L; nitisinone-treated AKU mean [±SD] = 45[±23] µmol/L). Biliary tyrosine, 3(4-hydroxyphenyl)pyruvic acid (HPPA) and 3(4-hydroxyphenyl)lactic acid (HPLA) are also increased on nitisinone. Urine was confirmed as the dominant elimination route of HGA in untreated AKU, but with indication of biliary excretion. These data provide new insights into pathways of phe-tyr metabolite biodistribution and metabolism, showing for the first time that hepatobiliary excretion contributes to the total pool of metabolites in this pathway. Our data suggest that biliary elimination of organic acids and other metabolites may play an underappreciated role in disorders of metabolism. We propose that our finding of approximately 3.8 times greater urinary HGA excretion in AKU mice compared with patients is one reason for the lack of extensive tissue ochronosis in the AKU mouse model.

Estimating the prevalence of potential and actionable drug-gene interactions in Irish primary care: A cross-sectional study.

AIMS: Pharmacogenetics (PGx) is increasingly recognized as a strategy for medicines optimisation and prevention of adverse drug reactions. According to guidelines produced by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG), most medicines with drug-gene interactions (DGIs) are prescribed in primary care. This study aimed to estimate the prevalence of potential and actionable DGIs involving all medicines dispensed in Irish primary care. METHODS: Dispensings of 46 drugs to General Medical Services (GMS) patients in the Health Service Executive Primary Care Reimbursement Service Irish pharmacy claims database from 01 January 2021 to 31 December 2021 were analysed to estimate the national prevalence of total dispensings and incidence of first-time dispensings of drugs with potential DGIs according to the CPIC and/or DPWG guidelines. Phenotype frequency data from the UK Biobank and the CPIC were used to estimate the incidence of actionable DGIs. RESULTS: One in five dispensings (12 443 637 of 62 754 498, 19.8%) were medicines with potential DGIs, 1 878 255 of these dispensed for the first time. On application of phenotype frequencies and linked guideline based therapeutic recommendations, 2 349 055 potential DGIs (18.9%) required action, such as monitoring and guarding against maximum dose, drug or dose change. One in five (369 700, 19.7%) first-time dispensings required action, with 139 169 (7.4%) requiring a change in prescribing. Antidepressants, weak opioids and statins were most commonly identified as having actionable DGIs. CONCLUSIONS: This study estimated a high prevalence of DGIs in primary care in Ireland, identifying the need and opportunity to optimize drug therapy through PGx testing.

Modelling a Consultant Workforce for the United Kingdom: needs-based planning for Dental Public Health.

OBJECTIVE: To develop a needs-based workforce planning model to explore specialist workforce capacity and capability for the effective, efficient, and safe provision of services in the United Kingdom (UK); and test the model using Dental Public Health (DPH). BASIC RESEARCH DESIGN: Data from a national workforce survey, national audit, and specialty workshops in 2020 and 2021 set the parameters for a safe effective DPH workforce. A working group drawing on external expertise, developed a conceptual workforce model which informed the mathematical modelling, taking a Markovian approach. The latter enabled the consideration of possible scenarios relating to workforce development. It involved exploration of capacity within each career stage in DPH across a time horizon of 15 years. Workforce capacity requirements were calculated, informed by past principles. RESULTS: Currently an estimated 100 whole time equivalent (WTE) specialists are required to provide a realistic basic capacity nationally for DPH across the UK given the range of organisations, population growth, complexity and diversity of specialty roles. In February 2022 the specialty had 53.55 WTE academic/service consultants, thus a significant gap. The modelling evidence suggests a reduction in DPH specialist capacity towards a steady state in line with the current rate of training, recruitment and retention. The scenario involving increasing training numbers and drawing on other sources of public health trained dentists whilst retaining expertise within DPH has the potential to build workforce capacity. CONCLUSIONS: Current capacity is below basic requirements and approaching 'steady state'. Retention and innovative capacity building are required to secure and safeguard the provision of specialist DPH services to meet the needs of the UK health and care systems.

Temporal adaptations in the phenylalanine/tyrosine pathway and related factors during nitisinone-induced tyrosinaemia in alkaptonuria.

BACKGROUND: Adaptations within the phenylalanine (PHE)/tyrosine (TYR) pathway during nitisinone (NIT) are not fully understood. OBJECTIVE: To characterise the temporal changes in metabolic features in NIT-treated patients with alkaptonuria. PATIENTS AND METHODS: Serum (s) and 24-urine (u) homogentisic acid (sHGA, uHGA24), TYR (sTYR, uTYR24), PHE (sPHE, uPHE24), hydroxyphenylpyruvate (sHPPA, uHPPA24), hydroxyphenyllactate (sHPLA, uHPLA24) and sNIT were measured at baseline (V1) and until month 48 (V6) in 69 NIT-treated patients, recommended to reduce protein intake. The 24-h urine urea (uUREA24), creatinine (uCREAT24) and body weight were also measured. Amounts of tyrosine metabolites in total body water (TBW) were derived by multiplying the serum concentrations by 60% body weight, and sum of TBW and urine metabolites resulted in combined values (c). RESULTS: uUREA24 and uCREAT24 decreased between V1 and V6 during NIT, whereas body weight and sNIT increased. Linear regression coefficient between uUREA24 and uCREAT24 was extremely strong (R = 0.84). sPHE, TBWPHE and cPHE24 increased gradually from V1 to V6. A decrease in cTYR24/cPHE24, sTYR/sPHE and TBWTYR/TBWPHE was seen from V2 to V6. Serum, 24-urine and combined TYR, HPPA and HPLA either remained stable or decreased from V2 to V6. DISCUSSION: The gradual increase in PHE suggests adaptation to increasing TYR during NIT therapy. The decrease in protein intake resulted in decreased muscle mass and increased weight gain. CONCLUSION: Progressive adaptation by decreasing PHE conversion to TYR occurs over time during NIT therapy. A low protein diet results in loss of muscle mass but also weight gain suggesting an increase in fat mass.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

CONTEXT AND PURPOSE: There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. METHODS: IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. RESULTS: To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. CONCLUSIONS: Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. TRAIL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

Steroidogenesis in patients with adrenal incidentalomas: Extended steroid profile measured by liquid chromatography-mass spectrometry after ACTH stimulation and dexamethasone suppression.

OBJECTIVE: Describe the secretion and profile of adrenal steroids in patients with adrenal incidentalomas compared to control subjects. DESIGN, SETTING AND PARTICIPANTS: A prospective study, 73 patients with adrenal incidentalomas, 21 bilateral and 52 unilateral and 34 matched controls in University Hospital. METHODS: Collect fasting blood sample before and 60 min after ACTH test (250 µg IV). One week later, perform overnight 1 mg dexamethasone test. The following steroids were measured by liquid chromatography-mass spectrometry (LC-MS): pregnenolone, 17-OH pregnenolone, 17-OH progesterone, 11-deoxycorticosterone, 11-deoxyortisol, 21-deoxycortisol, corticosterone, cortisol, androstenedione and aldosterone. RESULTS: Mean baseline serum cortisol was higher in incidentalomas, bilateral 361 ± 124, (range 143-665) nmol/L,(p < .0001), unilateral 268 ± 89 3.2 (range 98-507) nmol/L (p < .019) compared to controls 207 ± 100 (range 72-502) nmol/L. ACTH stimulation showed significantly higher levels in bilateral and unilateral cases compared to controls. After dexamethasone, mean serum cortisol levels suppressed in bilaterals 89 ± 69 (range 30-3) nmol/L (p < .0001), 58 ± 52 (range 16-323) nmol/L in unilateral (p < .01) compared to 26 ± 9 (range 7-46) nmol/L in controls. Mean baseline serum corticosterone was higher in bilateral 9.3 ± 4.8 (range 2.4-18.4) nmol/L (p < .005) and unilateral 7.3 ± 5.7 (range 0.1-30.3) nmol/L (p < .01) compared to controls 4.2 ± 2.4 (range 1.1-10.2) nmol/L, after ACTH stimulation significantly increased to higher levels in bilateral (p < .0002) and unilateral cases (p < .044) compared to controls. After dexamethasone, mean levels were 2.5 ± 2.6 (range 0.5-12.5) nmol/L in bilateral (p < .0006), 1.5 ± 1.6 (range 0.3-9.3) nmol/L in unilateral (p < .09) and 0.75 ± 0.46 (range 0.1-2.1) nmol/L in controls. Mean baseline serum 11-deoxycorticosterone (DOC) was higher in bilaterals 0.32 ± 0.23 (range 0.08-1.1) nmol/L (p < .03) compared to controls 0.15 ± 0.21 (range 0.08-1.1) nmol/L. ACTH stimulation increased levels to 3.27 ± 1.72 (range 0.5-7.4) nmol/L in bilateral cases compared to controls 1.369 ± 1.53 (range 0.1-7.1) nmol/L (p < .0001). Dexamethasone decreased levels to baseline (p ns). There were significant differences in serum 21-deoxycortisol (p < .0002) and serum pregnenolone (p < .004) only after ACTH stimulation. CONCLUSIONS: There is increased activity in several steroid biosynthesis pathways and higher steroid levels in bilateral compared to unilateral cases and evidence of hypercortisolism in 30% unilateral and 62% of bilateral incidentalomas.

Reference range for 24-h urine calcium, calcium/creatinine ratio, and correlations with calcium absorption and serum vitamin D metabolites in normal women.

A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30-300 mg and 10-285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100-300 mg; there is a need for them to update their age- and race-specific ranges. INTRODUCTION: Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most "laboratory normal ranges" based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25-45 years and older women age 55-90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites. METHODS: Data from 3 studies was collected on 959 normal black and white women, ages 25-87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption. Urine calcium and creatinine were measured on an auto-analyzer. Calcium absorption was measured by a single isotope method. Serum 25OHD and 1,25(OH)2D were measured by competitive protein binding assay or radioimmunoassay. Because 24-h urine calcium did not fit a normal distribution, non-parametric methods were used to determine the 95% reference interval (RI) and 90% non-parametric confidence intervals (CI) calculated for groups. RESULTS: The 95% reference intervals for 24-h urine calcium for women were as follows: black older 7-225 mg, black younger 8-285 mg; white older 37-275 mg, and white younger 23-287 mg. In older white women, 24-h urine calcium was significantly correlated with serum 1,25(OH)2 D, r = 0.23, p < 0.001, calcium intake r = 0.12, p = 0.001, and calcium absorption r = 0.18, p = 0.003, but not serum 25OHD r = 0.07, p = 0.06. CONCLUSIONS: The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.

Frequency, diagnosis, pathogenesis and management of osteoporosis in alkaptonuria: data analysis from the UK National Alkaptonuria Centre.

Osteoporosis and fractures are common features of alkaptonuria. INTRODUCTION: A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU. METHODS: Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated. RESULTS: Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p < 0.05). CT LS showed an inverse relationship with fractures (R = - 0.28; p < 0.05). CT LS was significantly lower in the fracture group (p < 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p < 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p < 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p < 0.05). CONCLUSIONS: Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.

Irritant contact dermatitis in healthcare workers as a result of the COVID-19 pandemic: a cross-sectional study.

COVID-19 healthcare workers (HCWs) require frequent handwashing and use of personal protective equipment (PPE) to prevent infection. However, evidence is emerging that these practices are causing adverse effects on their skin integrity. A single-centre, cross-sectional study of HCWs from an Irish hospital was undertaken to evaluate the degree of COVID-19-related irritant contact dermatitis (ICD) between April and May 2020. Of 270 participants surveyed, 223 (82.6%) reported symptoms of ICD. The hands were the most commonly affected site (76.47%) and the most frequently reported symptom was dry skin (75.37%). Nearly all (268; 99.26%) HCWs had increased hand-washing frequency, but 122 (45.35%) did not use emollients. In the ICD group, 24.7% cited a history of dermatitis compared with 4.3% of unaffected staff (P < 0.001). The ICD group recorded PPE usage for an average of 3.15 h compared with the non-ICD group at 1.97 h (P = 0.21). Promoting awareness of COVID-19-related ICD is vital to highlight prevention and treatment for frontline staff.

Covid-19 presentation among symptomatic healthcare workers in Ireland.

BACKGROUND: It is recognized that healthcare workers (HCWs) are at high risk of contracting Covid-19. It is incumbent on occupational health staff to recognize potential symptoms of Covid-19 among HCWs. AIMS: The aims of the study were to describe the presenting symptoms of HCWs who developed Covid-19 in Ireland, and to estimate the odds of specific symptoms being associated with a positive Covid-19 polymerase chain reaction (PCR) result. METHODS: A retrospective chart review of all symptomatic HCWs who self-presented for Covid-19 testing in Cork from March to May 2020 was conducted. A sex-matched case-control study was carried out to compare presenting features among those who tested positive compared to those who tested negative. Univariate and multivariable-adjusted conditional logistic regression models were run using Stata 15.0 to identify the symptoms associated with positive Covid-19 swab results. RESULTS: Three hundred and six HCWs were included in the study; 102 cases and 204 controls. Common presenting features among cases were fever/chills (55%), cough (44%) and headache (35%). The symptoms which were significantly associated with a positive Covid-19 swab result were loss of taste/smell (adjusted odds ratio [aOR] 12.15, 95% confidence interval [CI] 1.36-108.79), myalgia (aOR 2.36, 95% 1.27-4.38), fatigue (aOR 2.31, 95% CI 1.12-4.74), headache (aOR 2.11, 95% CI 1.19-3.74) and fever/chills (aOR 1.88, 95% CI 1.12-3.15). CONCLUSIONS: Fever, fatigue, myalgia, loss of taste/smell and headache were associated with increased odds of a Covid-19 diagnosis among symptomatic self-referred HCWs compared with those had negative swab results. Testing criteria for HCWs should reflect the broad range of possible symptoms of Covid-19.

Editorial - Delivering Better Oral Health 2021 - What's new and where next?

Delivering Better Oral Health (DBOH) was fi rst published in 2007 (Department of Health et al., 2007) at the request of the Department of Health to the British Association of Community Dentistry (BASCD). It was led by Dr Sue Gregory, who was at that time President of BASCD; and, thereafter, appointed Deputy Chief Dental Officer for England. The purpose of the document was to support dental teams in a more preventive approach to dental care based on the best available evidence. Practitioners have access to an enormous amount of information, and it was intended that DBOH would provide a simple guide to the evidence, explaining what the research meant in practical terms for the preventive advice and treatment of their patients. The approach promoted preventive care for all patients and additional support for those most at risk of poor oral health. DBOH was to be a living document, regularly updated. It was revised in 2009 and 2014, when after the Health and Social Care Act (2012), Public Health England took on the leadership of its development. In 2017 revisions responsed to changes in guidance; the publication by the Scientific Advisory Committee on Nutrition of the Carbohydrates and Health Report (SACN, 2015) which led to a revised healthier eating section and the Chief Medical Officers' (2016) new guidelines on alcohol were also incorporated.

Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.

BACKGROUND: Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. METHODS: We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. RESULTS: A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. CONCLUSIONS: Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).

Correlation Between Size and Function of Unilateral and Bilateral Adrenocortical Nodules: An Observational Study.

OBJECTIVE. Adrenal incidentalomas occur in 5% of adults and can produce autonomous cortisol secretion that increases the risk of metabolic syndrome and cardiovascular disease. The objective of our study was to evaluate the relationship between adrenal nodule size measured on CT and autonomous cortisol secretion. SUBJECTS AND METHODS. In a prospective study of 73 patients 22-87 years old with incidentalomas, unilateral in 52 patients and bilateral in 21 patients, we measured maximum nodule diameter on CT and serum cortisol levels at 8:00 am, 60 minutes after the adrenocorticotropic hormone stimulation test, and after the dexamethasone suppression test. We also studied 34 age-, sex-, and body mass index-matched control subjects. Statistics used were Spearman correlation coefficients, t tests, ANOVA test, and multivariate analysis. RESULTS. The mean maximum diameter of unilateral nodules measured on CT was larger on the right (2.47 ± 0.98 [SD] cm) than on the left (2.04 ± 0.86 cm) (p = 0.01). In the bilateral cases, the mean diameter of the right nodules was 2.69 ± 0.93 cm compared with 2.13 ± 0.89 cm on the left (p = 0.06). Mean baseline serum cortisol level was significantly higher in the patients with incidentalomas (bilateral, 13.1 ± 4.5 mcg/dL [p < 0.001]; unilateral, 9.7 ± 3.2 mcg/dL [p = 0.019]) than in the control subjects (7.5 ± 3.6 mcg/dL). After dexamethasone suppression test, serum cortisol levels were suppressed to less than 1.8 mcg/dL in 100% of control subjects, 33% of patients with bilateral incidentalomas, and 62% of patients with unilateral incidentalomas (p < 0.001). There were significant correlations between maximum nodule diameter on CT and serum cortisol levels after the dexamethasone suppression test (ρ = 0.500; p < 0.001) and at baseline (ρ = 0.373; p = 0.003). CONCLUSION. Increasing size of adrenal nodules is associated with more severe hyper-cortisolism and less dexamethasone suppression; these cases need further evaluation and possibly surgery because of increased risks of metabolic syndrome and cardiovascular mortality.

Peer review audit of non-specialist occupational physician reports.

BACKGROUND: With declining specialist occupational physician (OP) numbers, there is increasing recognition of the importance of non-specialist physicians in occupational health (OH) service delivery, yet to date, this physician group remains understudied and their competency requirements poorly understood. AIMS: To evaluate the quality of a sample of non-specialist OH reports and compare these with specialist reports. METHODS: A retrospective peer review audit of a convenience sample of 200 consecutive non-specialist and specialist OH reports from an Irish OH service using an assessment form based on the modified Sheffield Assessment Instrument for Letters SAIL(OH)1. RESULTS: Of the 200 peer reviewed OH reports, 159 (80%) were from non-specialists. For all questions, 87% and above of non-specialist reports were 'satisfactory' or 'above expected'. On the overall assessment, out of 10, the mean non-specialist report score was 6.8 (standard deviation (SD) 3-10) and the specialist score was 7.3 (SD 3-10). Comparatively, non-specialist reports highlighted legal/ethical issues marginally more and adhered slightly better to contractual/ethical/legal boundaries, while specialist reports fared better in addressing manager's questions, in their structure and clarity and in covering all significant aspects of the case, particularly if the case was complex. CONCLUSIONS: Our findings demonstrate a high standard of OH report quality in this sample of non-specialist OPs that is consistent across all key OH report components. Potential development areas are also identified that can inform education/training tailored to this physician group and assist in competency standard-setting.

Dental Public Health Education in Europe: a survey of European Dental Schools to determine current practice and inform a core undergraduate programme.

OBJECTIVE: Describe current Dental Public Health [DPH] curricula content and delivery across European dental schools and ascertain views on a core undergraduate curriculum for dental students. RESEARCH DESIGN: Survey of European dental schools, informed by professional and academic literature and European Association for Dental Public Health [EADPH] Special Interest Working Group discussions. Questionnaires were distributed electronically, by post, and via EADPH network members, to the Deans of 252 dental schools in Europe. E-mail reminders were sent to non-responders. SETTING: European Dental Schools. RESULTS: Around half (n=124, 49%) out of a possible 252 schools responded, all of which reported having some DPH education. Two-thirds reported having a dedicated DPH department. Education was delivered by a variety of staff including those trained in paediatric and preventive dentistry. There were differing degrees of integration within the undergraduate programme and substantial variability in topics, teaching methods and approaches to assessment. Key components of the curriculum supported by respondents were: DPH philosophy and approach, population demography and health, health promotion and disease prevention, health care systems, the dental workforce and planning for health and oral health. Respondents were generally in favour of improving current teaching and shaping a core DPH curriculum for Europe. CONCLUSIONS: Amongst those who completed the questionnaire, there was a general agreement on the need for a core Dental Public Health curriculum for European dentists. Given the variation across Europe, increased awareness and prioritisation of the subject is required, facilitated by collaborative support.

Have Legislative Interventions Impacted the Incidence of Needlestick Injuries?

Introduction The aim of this study was to examine the impact the EU Directive for the Prevention of Sharps injuries had on the incidence of needlestick injuries (NSI) in Ireland. Methods A five-year retrospective study prior to, and after the introduction of these regulations, was conducted. Secondary data from the Occupational Health Department's annual NSI reports were used. The population studied were healthcare workers who reported a NSI from 2013 to 2017. Results The incidence of NSI varied from 157 in 2017 to 207 in 2014. 'Miscellaneous needles' was the category which caused the most NSI (23%). 'Disposable needles with syringes' accounted for 20% of all NSI before the legislation; this figure was reduced to 12-15% after the regulations were introduced. Conclusion The EU regulations did not reduce the incidence of NSI. A lower incidence of NSI was reported from 'disposable needles with syringes' after the implementation of the regulations.

Work-Related Stress Induced Takotsubo Cardiomyopathy.

Aim To report a case of Takotsubo cardiomyopathy secondary to a verbal altercation in an employee who presented with chest pain. Methods The clinical history was obtained from the patient's occupational health record and correspondence from her treating cardiologist. Results The patient was diagnosed with Takotsubo cardiomyopathy following investigations for chest pain. Her echocardiogram was diagnostic. She was treated with beta blockers and advised to have complete rest; she remained out of work for six months. Conclusion There are few published cases of work related Takotsubo cardiomyopathy; it poses a challenge to physicians to be cognisant of this condition in a case of chest pain following emotional turmoil.

Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials.

BACKGROUND: It is questionable as to whether total serum 25 hydroxyvitamin D (T25D) levels are lower in African Americans. We measured serum T25D, free 25hydroxyvitamin D (F25D) and serum parathyroid hormone (PTH) in African American and Caucasian women and studied the effect of vitamin D dosing to determine if differences by race or age occur. METHODS: Healthy young and older Caucasian and African American women who were vitamin D insufficient were randomized in two clinical trials to escalating daily doses of vitamin D from 400 to 4800 IU and placebo for 12 months. RESULTS: Baseline F25D and T25D were significantly lower in young but not older African American compared to Caucasian women. At baseline, the rate of change, or slope, in F25D with T25D was significantly greater in younger women than in older women, but difference in the rate of change in F25D with T25D is similar in African American and Caucasian women. After vitamin D supplementation, there was an increase in F25D, and the dose response was not significantly different by age or race. The ratio of F25D/T25D decreased in all groups once T25D exceeded ~60 nmol L-1 . There was a progressive decrease in serum PTH with increasing vitamin D doses and the per cent change was similar for F25D and T25D. CONCLUSION: Serum F25D and T25D are lower in younger African American women, and since dietary vitamin D is similar in the groups, it is likely that the cause of low serum 25OHD in African American women is due to reduced UV exposure and reduced skin production of vitamin D.

Raman Spectroscopy identifies differences in ochronotic and non-ochronotic cartilage; a potential novel technique for monitoring ochronosis.

OBJECTIVE: Alkaptonuria (AKU) is a rare, inherited disorder of tyrosine metabolism, where patients are unable to breakdown homogentisic acid (HGA), which increases systemically over time. It presents with a clinical triad of features; HGA in urine, ochronosis of collagenous tissues, and the subsequent ochronotic arthritis of these tissues. In recent years the advance in the understanding of the disease and the potential treatment of the disorder looks promising with the data on the efficacy of nitisinone. However, there are limited methods for the detection and monitoring of ochronosis in vivo, or for treatment monitoring. The study aim was to test the hypothesis that Raman spectra would identify a distinct chemical fingerprint for the non-ochronotic, compared to ochronotic cartilage. DESIGN: Ochronotic and non-ochronotic cartilage from human hips and ears were analysed using Raman spectroscopy. RESULTS: Non-ochronotic cartilage spectra were similar and reproducible and typical of normal articular cartilage. Conversely, the ochronotic cartilage samples were highly fluorescent and displayed limited or no discernible Raman peaks in the spectra, in stark contrast to their non-ochronotic pairs. Interestingly, a novel peak was observed associated with the polymer of HGA in the ochronotic cartilage that was confirmed by analysis of pigment derived from synthetic HGA. CONCLUSION: This technique reveals novel data on the chemical differences in ochronotic compared with non-ochronotic cartilage, these differences are detectable by a technique that is already generating in vivo data and demonstrates the first possible procedure to monitor the progression of ochronosis in tissues of patients with AKU.