Calcium requests in a primary care; An observational audit of biochemical requests and frequency of abnormal results.

BACKGROUND/AIMS: This aim of this audit was to assess the extent of serum calcium testing and the frequency of hypercalcaemia in the primary care setting. We also assessed the appropriateness of subsequent investigations with repeat serum calcium and PTH testing if hypercalcaemia was identified. METHODS: All laboratory requests for adjusted calcium and PTH samples sent from primary care in Glasgow were analysed over a 12 month period. This covered approximately 125 GP practices and a patient population of over 590,000. RESULTS: There were 78,845 requests for adjusted calcium and 2053 PTH requests from 62,745 patients aged 16-105 years (median age 57, IQ range 30 years). Of these requests 1423 (2.3%) of patients had biochemical evidence of hypercalcaemia (adjusted calcium ≥ 2.61 mmol/L). Of the 1423 patients with hypercalcaemia, 368 patients (45.8%) had a single raised calcium level that was within the normal range on repeat testing. Of the 400 patients with persistent hypercalcaemia on 2 or more samples, 210 (52.5%) had a PTH measured. Eight patients had a PTH < 2.0 pmol/L, whilst 202 (96.1%) had a PTH ≥ 2.0 pmol/L (range 2.1-106.1 pmol/L). CONCLUSIONS: Serum calcium was checked in 10.6% of the population per year within primary care. In the 2.4% with a raised calcium on initial testing, approximately half (45.8%) will normalise on repeat testing. Of those who remained persistently hypercalcaemic, only half (52.5%) had a PTH measured and the majority (96.1%) were in keeping with primary hyperparathyroidism being the most common cause of hypercalcaemia.

National population prevalence of antibodies to SARS-CoV-2 in Scotland during the first and second waves of the COVID-19 pandemic.

OBJECTIVES: Studies that measure the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('seroprevalence') are essential to understand population exposure to SARS-CoV-2 among symptomatic and asymptomatic individuals. We aimed to measure seroprevalence in the Scottish population over the course of the COVID-19 pandemic - from before the first recorded case in Scotland through to the second pandemic wave. STUDY DESIGN: The study design of this study is serial cross sectional. METHODS: We tested 41,477 residual samples retrieved from primary and antenatal care settings across Scotland for SARS-CoV-2 antibodies over a 12-month period from December 2019-December 2020 (before rollout of COVID-19 vaccination). Five-weekly rolling seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Temporal trends in seroprevalence estimates and weekly SARS-CoV-2 notifications were compared. RESULTS: Five-weekly rolling seroprevalence rates were 0% until the end of March, when they increased contemporaneously with the first pandemic wave. Seroprevalence rates remained stable through the summer (range: 3%-5%) during a period of social restrictions, after which they increased concurrently with the second wave, reaching 9.6% (95% confidence interval [CI]: 8.4%-10.8%) in the week beginning 28th December in 2020. Seroprevalence rates were lower in rural vs. urban areas (adjusted odds ratio [AOR]: 0.70, 95% CI: 0.61-0.79) and among individuals aged 20-39 years and 60 years and older (AOR: 0.74, 95% CI: 0.64-0.86; AOR: 0.80, 95% CI: 0.69-0.91, respectively) relative to those aged 0-19 years. CONCLUSIONS: After two waves of the COVID-19 pandemic, less than one in ten individuals in the Scottish population had antibodies to SARS-CoV-2. Seroprevalence may underestimate the true population exposure as a result of waning antibodies among individuals who were infected early in the first wave.

The effect of magnesium administration on erythrocyte transketolase activity in alcoholic patients treated with thiamine.

BACKGROUND AND AIMS: Chronic alcoholic patients are at increased risk of developing deficiencies of thiamine and magnesium. Thiamine is an essential co-factor for a number of enzymes involved in carbohydrate metabolism and requires optimal levels of magnesium for biological function. However, whilst thiamine supplementation is well established for the treatment of alcoholic patients, the importance of magnesium is often overlooked. We describe the effect of concurrent thiamine and magnesium administration on the activity of the thiamine-dependent enzyme erythrocyte transketolase in a cohort of chronic alcoholic patients. METHODS: Baseline erythrocyte transketolase activities were measured on blood samples collected from 36 chronic alcoholic patients presenting acutely to the Accident and Emergency department. Patients received either intravenous Pabrinex (thiamine) supplemented with magnesium sulphate (n = 18) or Pabrinex only (n = 18). Post-treatment bloods were collected for re-assessment of erythrocyte transketolase activity. The change in transketolase activities (pre-vs. post-treatment) between the two patient groups were compared by Mann-Whitney U test. RESULTS: The increase in transketolase activity following treatment in the cohort receiving Pabrinex supplemented with magnesium sulphate was significantly greater (p = 0.018) than that produced in the cohort receiving Pabrinex alone. CONCLUSION: In the acute management of a sample of chronic alcoholic patients, those receiving magnesium sulphate with Pabrinex have higher increases in erythrocyte transketolase activity compared with those receiving Pabrinex alone. We conclude that concurrent magnesium administration with Pabrinex may be required for enabling full efficacy of Pabrinex treatment, as demonstrated by its positive effect on erythrocyte transketolase activity.

Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency.

INTRODUCTION: Vitamin D insufficiency is common, however within individuals, not all manifest the biochemical effects of PTH excess. This further extends to patients with established osteoporosis. The mechanism underlying the blunted PTH response is unclear but may be related to magnesium (Mg) deficiency. The aims of this study were to compare in patients with established osteoporosis and differing degrees of vitamin D and PTH status : (1) the presence of Mg deficiency using the standard Mg loading test (2) evaluate the effects of Mg loading on the calcium-PTH endocrine axis (3) determine the effects of oral, short term Mg supplementation on the calcium-PTH endocrine axis and bone turnover. METHODS: 30 patients (10 women in 3 groups) were evaluated prospectively measuring calcium, PTH, Mg retention (Mg loading test), dietary nutrient intake (calcium, vitamin D, Mg) and bone turnover markers (serum CTX & P1CP). Multivariate analysis controlling for potential confounding baseline variable was undertaken for the measured outcomes. RESULTS: All subjects, within the low vitamin D and low PTH group following the magnesium loading test had evidence of Mg depletion [mean(SD) retention 70.3%(12.5)] and showed an increase in calcium 0.06(0.01) mmol/l [95% CI 0.03, 0.09, p=0.007], together with a rise in PTH 13.3 ng/l (4.5) [95% CI 3.2, 23.4, p=0.016] compared to baseline. Following oral supplementation bone turnover increased: CTX 0.16 (0.06) mcg/l [95%CI 0.01, 0.32 p=0.047]; P1CP 13.1 (5.7) mcg/l [95% CI 0.29, 26.6 p=0.049]. In subjects with a low vitamin D and raised PTH mean retention was 55.9%(14.8) and in the vitamin replete group 36.1%(14.4), with little change in both acute markers of calcium homeostasis and bone turnover markers following both the loading test and oral supplementation. CONCLUSIONS: This study confirms that in patients with established osteoporosis, there is also a distinct group with a low vitamin D and a blunted PTH level and that Mg deficiency (as measured by the Mg loading test) is an important contributing factor.

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis.

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD < or = 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.

Longitudinal changes in bone mineral density during normal pregnancy.

Pregnancy is a common physiological event that could affect peak bone mass and the risk of developing osteoporosis later in life. There have been few longitudinal studies over a complete reproductive cycle of any size to show whether bone mineral density (BMD) changes. We have measured BMD by dual-energy X-ray absorptiometry in 46 normal women before conception and then again immediately after delivery and compared them with 30 control women who failed to conceive. Fifteen women were osteopenic in preconceptual BMD, but there was no difference between those who did or did not become pregnant. During pregnancy there was a small and statistically nonsignificant decline in BMD at all sites. The decrease at the trochanteric region was 4.2%, while losses at other sites were about 1%. The decline at the trochanter exceeded the least significant change between two measurements (5.04%) in 17 women (40.5%) with significant changes within individuals being much less common at the other measurement sites. The nonpregnant controls showed small increases in BMD of 0.3%-1.9% but no woman lost more than the least significant change. At the trochanter there was a significant difference (P = 0.013) between those who did and did not become pregnant. There was a good correlation between changes in BMD at all sites and no significant difference in the slope of these correlations between the pregnant and control groups. Correlations with lumbar spine were total hip, r = 0.46, P = 0.0001; femoral neck, r = 0.49, P = 0.0005; and trochanter, r = 0.66, P < 0.0001.