Pharmacokinetics of cefiderocol during extracorporeal membrane oxygenation: A case report.

Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.

Clinical value of procalcitonin in critically ill patients infected by SARS-CoV-2.

Background Blood procalcitonin (PCT) levels usually increase during infectious diseases and might be helpful to differentiate bacterial from non-bacterial origin. COVID-19 patients could present co-infections at initial presentation in the Emergency Department and nosocomial infections during stay in the ICU. However, the published literature has not established whether PCT changes could aid in the diagnosis of infectious complication during the COVID-19 pandemic. Methods Retrospective, single-center, cohort study, including COVID-19 patients admitted between March and May 2020. The data were prospectively collected for department purposes; laboratory results were collected automatically at admission and during the whole patient admission. Results 56 patients were analyzed (female 32%, male 68%), 35 were admitted to ICU, and 21 received general ward care. 21 ICU patients underwent mechanical ventilation (88%), and 9 died during admission (26%). Non-survivors had higher initial blood PCT levels than survivors at ICU admission (p.

High prevalence of undiagnosed vertebral fractures in patients suffering from hip fracture at their hospital admission: weak concordance among observers.

BACKGROUND: Vertebral fracture is often underdiagnosed. Patients with hip fracture may suffer from vertebral fracture without knowing it. The diagnosis of vertebral fracture is sometimes difficult because there is no consensus regarding the definition of osteoporotic vertebral fracture, and several indexes may be used to diagnose it and the concordance between several observers may not be optimal. OBJECTIVE: To study the concordance in the diagnosis of vertebral fracture done by three different doctors: an orthopedic surgeon, a radiologist, and a bone mineral metabolism expert. METHODS: A lateral thoracic-lumbar spine X-Ray was performed in 177 patients suffering from hip fracture to assess the presence or absence of vertebral fractures. Three different observers applied Genant's criteria for it. Concordance between observers was measured using Cohen's kappa coefficient. RESULTS: Patients suffering from hip fractures have undiagnosed vertebral fractures in a range that varies from 41.8 to 47.5% depending on the observer. The concordance in the diagnosis of vertebral fractures is quite low, ranging a Cohen's kappa coefficient from 0.43 to 0.55 and a percentage of concordance varying from 64 to 72%. The best concordance was found between observers 1 and 3. DISCUSSION: Depending on the observer who made the diagnosis, the prevalence of previously undiagnosed vertebral fractures in patients with HF varied widely. We selected three different observers to assess the possible differences in the diagnosis of vertebral fractures among these patients and using the same method (Genant's semi-quantitative assessment), surprisingly, there was little concordance among the three of them. CONCLUSION: Patients with hip fracture have high prevalence of undiagnosed vertebral fractures. The diagnosis of these fractures varies widely depending on the observers and the Cohen's kappa coefficient and percentage of concordance is rather low.

Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics.

The recent increase in legality of Cannabis Sativa L. has led to interest in developing new varieties with unique aromatic or effect-driven traits. Selectively breeding plants for the genetic stability and consistency of their secondary metabolite profiles is one application of phenotyping. While this horticultural process is used extensively in the cannabis industry, few studies exist examining the chemical data that may differentiate phenotypes aromatically. To gain insight into the diversity of secondary metabolite profiles between progeny, we analyzed five ice water hash rosin extracts created from five different phenotypes of the same crossing using comprehensive 2-dimensional gas chromatography coupled to time-of-flight mass spectrometry, flame ionization detection, and sulfur chemiluminescence detection. These results were then correlated to results from a human sensory panel, which revealed specific low-concentration compounds that strongly influence sensory perception. We found aroma differences between certain phenotypes that are driven by key minor, nonterpenoid compounds, including the newly reported 3-mercaptohexyl hexanoate. We further report the identification of octanoic and decanoic acids, which are implicated in the production of cheese-like aromas in cannabis. These results establish that even genetically similar phenotypes can possess diverse and distinct aromas arising not from the dominant terpenes, but rather from key minor volatile compounds. Moreover, our study underscores the value of detailed chemical analyses in enhancing cannabis selective breeding practices, offering insights into the chemical basis of aroma and sensory differences.

Osteoporosis and metabolic syndrome according to socio-economic status, contribution of PTH, vitamin D and body weight: The Canarian Osteoporosis Poverty Study (COPS).

BACKGROUND: Poverty is associated with a great number of diseases, but the prevalence of vitamin D deficiency, secondary hyperparathyroidism and the potential association of osteoporosis, osteoporotic fractures and metabolic syndrome in this situation are less well known. OBJECTIVE: To evaluate the associations between poverty, bone density, fragility fractures and metabolic syndrome in a population of southern European postmenopausal women. Also, to assess the potential role of vitamin D and parathyroid hormone (PTH) levels in these associations. METHOD: Cross-sectional study was carried out in 1 250 postmenopausal Caucasian Spanish women. The socio-economic status of the participants was determined after a personal interview, according to the criteria of the Spanish Institute of Statistics. Participants were divided into two socio-economic levels: low (poverty) and medium or high socioeconomic level. The study protocol included a health questionnaire, a complete physical examination, lateral radiograph of the dorsal and lumbar spine and measurement of bone mineral density (BMD) at the lumbar spine (L2-L4) and proximal femur. Fasting blood was obtained to measure 25-hydroxy-vitamin D (25-OHD), intact PTH and selected biochemical variables. RESULTS: Low socio-economic status was associated with 25-OHD insufficiency, higher values of PTH, higher body weight and body mass index (BMI), lower values of BMD at the lumbar spine and a higher prevalence of fragility fractures, both vertebral and nonvertebral. Poverty was also associated with higher prevalence of metabolic syndrome, but this association was driven mainly by the higher BMI and not by poverty itself. Both vitamin D insufficiency and elevated PTH were consistently related to poverty and osteoporotic fractures. CONCLUSIONS: Poor postmenopausal women in southern Europe have a high prevalence of metabolic syndrome and osteoporotic fractures. Poverty was associated with higher BMI and metabolic syndrome on the one hand and, on the other, with 25OHD insufficiency, higher PTH levels and osteoporosis. 25OHD insufficiency and/or secondary hyperparathyroidism do not have a significant influence on the presence of metabolic syndrome in this population.

Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis.

Cannabis sativa L. produces a wide variety of volatile secondary metabolites that contribute to its unique aroma. The major volatile constituents include monoterpenes, sesquiterpenes, and their oxygenated derivates. In particular, the compounds ß-myrcene, D-(+)-limonene, ß-caryophyllene, and terpinolene are often found in greatest amounts, which has led to their use in chemotaxonomic classification schemes and legal Cannabis sativa L. product labeling. While these compounds contribute to the characteristic aroma of Cannabis sativa L. and may help differentiate varieties on a broad level, their importance in producing specific aromas is not well understood. Here, we show that across Cannabis sativa L. varieties with divergent aromas, terpene expression remains remarkably similar, indicating their benign contribution to these unique, specific scents. Instead, we found that many minor, nonterpenoid compounds correlate strongly with nonprototypical sweet or savory aromas produced by Cannabis sativa L. Coupling sensory studies to our chemical analysis, we derive correlations between groups of compounds, or in some cases, individual compounds, that produce many of these diverse scents. In particular, we identified a new class of volatile sulfur compounds (VSCs) containing the 3-mercaptohexyl functional group responsible for the distinct citrus aromas in certain varieties and skatole (3-methylindole) as the key source of the chemical aroma in others. Our results provide not only a rich understanding of the chemistry of Cannabis sativa L. but also highlight how the importance of terpenes in the context of the aroma of Cannabis sativa L. has been overemphasized.

Discriminative ability of heel quantitative ultrasound in postmenopausal women with prevalent vertebral fractures: application of optimal threshold cutoff values using classification and regression tree models.

Quantitative ultrasound (QUS) of the heel has been proposed as a screening tool to evaluate the bone status and risk of osteoporotic fragility fractures. The aim of this study was to define threshold values that would maximize the predictive ability of QUS to discriminate subjects with vertebral fractures using the classification and regression trees (CART) models. A cross-sectional analysis was made of a cohort of 1,132 postmenopausal women with a mean age of 58 years. A total of 205 women (18.1 %) presented with a history of vertebral fracture. For all patients, a questionnaire of osteoporosis risk factors was given and measurements of the heel QUS and bone mineral density at the lumbar spine and the proximal femur, obtained by dual-energy X-ray absorptiometry (DXA), were made. Spinal radiographs were assessed for vertebral fractures. Sensitivity, specificity, predictive values, likelihood ratios, and receiver operator characteristics (ROC) curve QUS values were calculated using the optimal threshold identified in the CART models. Cutoff values calculated from best CART model (i.e., a QUS index >90.5 %) yielded a sensitivity of 80.3 % (95 % CI 69.2-88.1), a negative predictive value of 94 % (95 % CI 90.1-96.5), and a specificity of 68.8 % (95 % CI 63.3-73.8). This cutoff value would obviate the need to perform DXA in 32.8 % of the women of our population at risk for vertebral fractures. The area under the ROC curve of the best model was 0.8071. QUS was shown to discriminate between women with and without a history of vertebral fracture and constitutes a useful tool for assessing vertebral fracture risk. The application of decision trees (CART analyses) was helpful to define the optimal threshold QUS values.

Discriminative ability of heel quantitative ultrasound in postmenopausal women with prevalent low-trauma fractures: application of optimal threshold cutoff values using CART models.

Quantitative ultrasound (QUS) of the heel has been proposed as a screening tool to evaluate the bone status and risk of osteoporotic fragility fractures. The aim of this study was to define threshold values of QUS that would maximize the predictive ability of this technique to discriminate subjects with fragility fractures. A cross-sectional analysis was made of a cohort of 1132 postmenopausal women with a mean age of 58 yr. A total of 361 women (31.9%) presented with a history of osteoporotic fracture. Most fractures (74.1%) were nonvertebral. For all patients, a questionnaire of osteoporosis risk factors and measurements of the heel QUS and bone mineral density at the lumbar spine and the proximal femur obtained by dual-energy X-ray absorptiometry (DXA) were assessed. Spinal radiographs were assessed for fractures and historical nonvertebral fragility fractures. Sensitivity, specificity, predictive values, likelihood ratios, and receiver operator characteristic (ROC) curve QUS values were calculated using the optimal threshold identified in the classification and regression trees (CART) models. Cutoff values calculated from the best CART model (i.e., a quantitative ultrasound index (QUI) greater than 88.5% in women aged 58 yr or older) yielded 88.8% (95% confidence interval [CI]: 81.4-93.5) for sensitivity, a negative predictive value of 93.8 (95% CI: 89.4-96.4), and 70.4% (95% CI: 64.6-75.7) for specificity. This cutoff value would obviate the need to perform DXA in 43.1% of the population. The area under the ROC curve of the best model was 0.8363 (95% CI: 0.8249-0.8477). In conclusion, QUS was shown to discriminate between women with and without a history of fragility fracture and constitutes a useful tool for assessing fracture risk. The application of decision trees (CART analyses) was helpful to define the optimal threshold QUS values.

Arsenic in freshwater fish in the Chihuahua County water reservoirs (Mexico).

Water reservoirs in Chihuahua County, Mexico, are affected by some punctual and non-punctual geogenic and anthropogenic pollution sources; fish are located at the top of the food chain and are good indicators for the ecosystems pollution. The study goal was to: (i) determine arsenic concentration in fish collected from the Chuviscar, Chihuahua, San Marcos and El Rejon water reservoirs; (ii) to assess if the fishes are suitable for human consumption and (iii) link the arsenic contents in fish with those in sediment and water reported in studies made the same year for these water reservoirs. Sampling was done in summer, fall and winter. The highest arsenic concentration in the species varied through the sampling periods: Channel catfish (Ictalurus punctatus) with 0.22 ± 0.15 mg/kg dw in winter and Green sunfish (Lepomis cyanellus) with 2.00 ± 0.15 mg/kg dw in summer in El Rejon water reservoir. A positive correlation of arsenic contents was found through all sampling seasons in fish samples and the samples of sediment and water. The contribution of the weekly intake of inorganic arsenic, based on the consumption of 0.245 kg fish muscles/body weight/week was found lower than the acceptable weekly intake of 0.015 mg/kg/body weight for inorganic arsenic suggested by FAO/WHO.

Vasopressin antagonist efficacy and safety in volume-overloaded critically ill patients: a new therapeutic alternative.

Objectives: To assess tolvaptan's efficacy and safety in critical care patients with volume overload. Methods: Prospective observational study. Twenty-eight patients in the recovery phase from multiple organ failure and with volume overload refractory to conventional therapy treated with tolvaptan were included. Results: Patients received an initial daily dose of 3.75 (n=1), 7.5 (n=8) and 15 (n=19) mg of tolvaptan. Median treatment duration was 2 days (range: 1 to 12). All patients presented an increase in 24 hours diuresis after the first dose (median increase from baseline (IQR)=1114 (285-1943) mL), with a median net daily fluid loss of 1007 mL (456-2380) mL after 24 hours. High diuretic efficacy (daily fluid loss higher than 0.5 L with tolvaptan first dose) was detected in 18 patients (64.3%). Initial hyponatraemia was present in 16 (57.1%) patients, while overly rapid correction with tolvaptan treatment occurred in two patients without clinical consequences. Two patients presented hypophosphataemia after treatment. Conclusion: Tolvaptan is an effective therapeutic option in critically ill patients with volume overload refractory to conventional diuretics. Further studies are required to evaluate its safety profile and its effect on short-term outcomes and mortality.

Are your engineers talking to one another when they should?

Communication may not be on managers' minds at companies that design complex, highly engineered products, but it should be. When mistakes take place, it's often because product-component teams fail to talk. The consequences can be huge: Ford and Bridgestone Firestone lost billions by not coordinating the design of the Explorer with the design of its tires. The major delays and cost overruns involved in the development of Airbus's A380 "superjumbo"--which most likely led to the CEO's exit--were a result of unforeseen design incompatibilities. To help managers mitigate such problems, the authors present a new application of the design structure matrix, a project management tool that maps the flow of information and its impact on product development. Drawing on research into how Pratt & Whitney handled the development of the PW4098 jet engine, they have developed an approach that uncovers (a) areas where communication should be occurring but is not (unattended interfaces, usually bad) and (b) areas where communication is occurring but has not been planned for (unidentified interfaces, usually good). After finding the unattended and unidentified interfaces, the next step is to figure out the causes of the critical ones. If a significant number of unattended interfaces cross organizational boundaries, executives may need to redraw organizational lines. Executives can then manage the remaining critical interfaces by extending the responsibilities of existing integration teams (those responsible for cross-system aspects, such as a jet engine's fuel economy) to include supervising the interaction, by dedicating teams to specific interfaces, or by formally charging teams already involved with the interfaces to oversee them. Finally, it's important to ensure that the teams are working with compatible design equipment; inconsistencies between CAD tools have cost Airbus dearly.

[Neonatal mortality in a regional perinatal hospital in Merida, Yucatan, 1995-2004 I. Analysis of the gross, specific rates]. / Mortalidad neonatal en un hospital perinatal regional de Mérida, Yucatán, de 1995 al 2004 I. Análisis de las tasas crudas y específicas.

OBJECTIVE: To evaluate the neonatal mortality and the specific neonatal mortality rates by groups of birthweight and gestacional age, at the Ignacio García Téllez National Medical Center which is a reference tertiary perinatal center of the Social Security Mexican Institute for the Yucatan Peninsula, along the period of 1995-2004. MATERIAL AND METHODS: A cohort of 46,297 live newborns was studied with birtweight of 500 grams or more, that were discharged between January 1st 1995 and December 31st 2004. Birthweight, gestational age, length of hospitalization, condition at discharge were captured in a data base. Triennial analysis of mortality was done. RESULTS: The proportion of neonates with birthweight <2,500 g increased and 19% neonates <1,000 g 50%, the increment was 21% for preterm neonates, 46% for immature, and 40% for those extremely immature. The early neonatal mortality rate diminished from 7.0 to 6.9, the late mortality from 3.0 to 2.2, the neonatal from 10.0 to 9.2/1,000 live newborn, the survival increased 232% in neonates with birthweight between 500-749 g, 25% between 750-999 g, 5.8% between 1,000-1,249 g, 8.2% between 1,250-1,499 g. The neonatal mortality decreased 31.8% from the expected, because the adjusted neonatal mortality rate was 13.5 compared with the observed 9.2/1,000 live newborn. CONCLUSIONS: There was a significant increase of the survival with lesser birthweight and gestational age, although it was not reflected in the brut neonatal mortality rate because there was an increase of the risk population.

Postmenopausal women with colles' fracture have lower values of bone mineral density than controls as measured by quantitative ultrasound and densitometry.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density (BMD) to evaluate the probability of Colles' fracture. Two-hundred eighty-nine postmenopausal women (62.3 +/- 8.7 yr) with (n = 76) and without (n = 213) Colles' fracture were studied. BMD of lumbar spine and proximal femur was evaluated in all women by dual-energy X-ray absorptiometry (DXA) and speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness in the calcaneus were measured by a Sahara ultrasonometer (Hologic). Patients suffering from Colles' fracture had lower values of BMD adjusted by height at the lumbar spine, L2-L4 (0.797 g/cm2 vs 0.860 g/cm2), femoral neck (0.685 g/cm2 vs 0.712 g/cm2 ), SOS (1518 m/sg vs 1525 m/sg), and stiffness (74.6 vs 77.7) (p < 0.05). Nevertheless, BUA values were similar in both groups. After stepwise logistic regression analysis, the area found under receiver operating characteristic (ROC) curves was 0.60 for L2L4 and 0.63 for a formula combining L2L4 and height. Our data suggest that patients suffering from Colles' fracture have lower values of BMD by DXA, SOS, and stiffness. However, the ability of these techniques to discriminate is low because the values for the area under ROC curve are 0.60 for L2-L4 and 0.63 for a formula derived of the combination of L2-L4 and height.

Spanish consensus on premature menopause.

INTRODUCTION: While we recognise that the term premature menopause is more accepted by most non-specialist health care providers and by the general population, 'primary ovarian insufficiency' (POI) is currently considered the most apposite term to explain the loss of ovarian function, because it better explains the variability of the clinical picture, does not specify definitive failure, and highlights the specific ovarian source. Its pathogenesis involves a congenital reduction in the number of primordial follicles, poor follicle recruitment, or accelerated follicular apoptosis. However, its cause is unknown in most cases. AIM: This guide analyses the factors associated with the diagnosis and treatment of POI and provides recommendations on the most appropriate diagnostic and therapeutic measures for women under 40 years of age who experience POI. METHODOLOGY: A panel of experts from various Spanish scientific societies related to POI (Spanish Menopause Society, Spanish Fertility Society, and Spanish Contraception Society) met to reach a consensus on these issues. RESULTS: Hormonal therapy (HT) is considered the treatment of choice to alleviate the symptoms of hypoestrogenism and to prevent long-term consequences. We suggest that HT should be continued until at least age 51, the average age at natural menopause. The best treatment to achieve pregnancy is oocyte/embryo donation. If a patient is to undergo treatment that will reduce her fertility, she should be informed of this issue and the available techniques to preserve ovarian function, mainly vitrification of oocytes.

Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis.

INTRODUCTION: The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. METHODS: This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2±8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67±9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17ß-estradiol levels by radioimmunoassay based on ultrasensitive methods. RESULTS: In the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38-82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02-1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. CONCLUSIONS: Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.

Bone mass, bone turnover, vitamin D, and estrogen receptor gene polymorphisms in male to female transsexuals: effects of estrogenic treatment on bone metabolism of the male.

The effect of chronic administration of estrogens on bone and mineral metabolism in men is not known. We have studied the effect of chronic administration of estrogens on bone mineral metabolism in a group of transsexual (TS) Canarian men, who were taking estrogens for a minimum of 3 years. This is a cross-sectional study of cases and controls and we studied biochemical markers of bone remodeling, bone mineral density (BMD), and selected biochemical and hormonal features. TS subjects had shorter stature than controls, and after adjusting for height and weight, we found that they had lower values for serum-free testosterone and higher values for BMD, both in the lumbar spine and in femoral neck. Biochemistry, bone remodeling markers, and calcitropic hormone values were similar in both groups. Finally, the distributions of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba) polymorphisms were also similar in both groups. We conclude that the chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD-both in lumbar spine and in femoral neck. We found no association between the transsexual phenotype and the distribution of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba).

Risk factors for prediction of inadequate response to antiresorptives.

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti-osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55-9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93-0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem.

Current evidence for recommendation of surgery, medical treatment and vitamin D repletion in mild primary hyperparathyroidism.

Management of patients with mild primary hyperparathyroidism (PHPT) has been widely discussed because most patients today do not have specific symptoms. While surgery is always an option, the recommendations for treatment have shifted, which mostly reflects changes in clinical practice. In this study, we aimed to evaluate evidence for the current recommendations concerning operation vs observation, repletion with vitamin D (VitD) and alternative medical management. Surgery is followed by normalisation of calcium and parathyroid hormone (PTH) and a decrease in bone turnover followed by an increase in bone mass. It is not known what the consequences would be for the frequency of fractures. Randomised studies have indicated beneficial effects of operation on quality of life (QoL), but the effects have been minor and inconsistent. Operation seems not to be superior to observation for cardiovascular risk factors. Although PHPT patients in average have slightly decreased plasma 25OH VitD, severe symptomatic VitD deficiency seems not to be a characteristic of PHPT patients in Europe. However, if present, we recommend VitD substitution before final decision on surgical treatment. It is unknown whether routine VitD supplementation should be offered preoperatively to all patients with mild PHPT or as part of long-term medical treatment. Targeted medical management could be an option for patients with contraindications to surgery. Antiresorptive therapy might be appropriate for patients with a low bone mass to prevent further bone loss. Calcimimetics could be tried to control serum calcium levels although there is no evidence of an effect on the hypercalcaemic symptoms or the QoL. Combined therapy with calcimimetics and alendronate could be considered for patients with hypercalcaemia and overt bone disease.