Spanish consensus on treat to target for osteoporosis.

To reach a Spanish expert consensus on a treat-to-target strategy in osteoporosis, a Delphi Consensus Study has been developed. Most of the experts (59.8%) were rheumatologist with a mean clinical experience of 21.3 years (SD 8.5). Consensus was achieved for 70% of the items. Therapeutic objectives, patient follow-up scheme, treatment failure criteria, and appropriate treatment choice for use in T2T strategy in Spain have been defined. INTRODUCTION: The paper aims to achieve a Spanish expert consensus on a treat-to-target (T2T) strategy in osteoporosis. METHODS: A scientific committee led the project and was involved in expert panel identification and Delphi questionnaire development. Two Delphi rounds were completed. The first-round questionnaire included 24 items and assessed, using a seven-point Likert scale, the experts' wish (W) and prognosis (P) in 5 years for each topic (applicability, therapeutic objectives, patient follow-up, and possible treatment to be prescribed). Items for which there was no consensus in the first round were included in the second round. Consensus was defined as ≥75% agreement (somewhat/mostly/entirely agree) or disagreement (somewhat/mostly/entirely disagree) responses. RESULTS: Of the experts, 112 and 106 completed the first and second rounds, respectively. 59.8% were rheumatologists with a mean clinical experience of 21.3 years (SD 8.5). Consensus was achieved for 70% of the items, and was established regarding the utility of a T2T strategy to define therapeutic objectives, optimal follow-up, and therapeutic algorithm. Participants agreed on the utility of the bone mineral density (BMD) value (T-score >-2.5 SD for spine and >-2.5/-2.0 SD for femoral neck), lack of fractures, and fracture risk (FRAX) as therapeutic objectives. For measuring BMD changes, consensus was achieved on the suitability of hip and femoral neck locations. Experts agreed to consider treatment failure as when a significant BMD gain could not be achieved, or when a new fracture occurs within 2-3 years. There was consensus that all proposed therapies should achieve a therapeutic target through T2T strategy (treatments with the highest consensus scores were denosumab and teriparatide). CONCLUSION: The therapeutic objectives, patient follow-up scheme, treatment failure criteria, and appropriate treatment choice for use in T2T strategy in Spain have been established by a panel of experts. Some aspects nevertheless still require further analysis.

Position statement for the management of comorbidities in psoriasis.

BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.

Effect of alendronate in elderly patients after low trauma hip fracture repair.

SUMMARY: One year of once weekly alendronate, when given shortly after the surgical repair of a hip fracture, produces reductions in bone markers and increases proximal femoral bone density. The therapy was well tolerated. INTRODUCTION: Hip fracture is the most devastating type of osteoporotic fracture and increases notably the risk of subsequent fractures. The aim of this paper was to evaluate the effects of 1 year therapy with a weekly dose of alendronate in the bone mineral density and bone markers in elderly patients after low trauma hip fracture repair. METHODS: Two hundred thirty-nine patients (81 +/- 7 years; 79.8% women) were randomized to be treated either with calcium (500 mg/daily) and vitamin D(3) (400 IU/daily; Ca-Vit D group) or with alendronate (ALN, 70 mg/week) plus calcium and vitamin D(3) (500 mg/daily and 400 IU/daily, respectively; ALN + Ca-Vit D group). RESULTS: One hundred forty-seven (61.5%) patients completed the trial. Alendronate increased proximal femoral bone mineral density (BMD) in the intention-to-treat analysis (mean difference (95% confidence interval); total hip 2.57% (0.67; 4.47); trochanteric 2.96% (0.71; 5.20), intertrochanteric 2.32% (0.36; 4.29)), but the differences were not significant in the BMD of the femoral neck (0.47%; (-2.03; 2.96) and the lumbar spine (0.69%; (-0.86; 2.23)). Bone turnover markers decreased during alendronate treatment. CONCLUSION: The present study demonstrates for the first time the anti-resorptive efficacy of alendronate given immediately after surgical repair in an elderly population with recent hip fracture. This effect should positively affect the rate of subsequent fractures.

Cost of achieving HbA1c and weight loss treatment targets with IDegLira vs insulin glargine U100 plus insulin aspart in the USA.

BACKGROUND: Compared with basal-bolus insulin therapy (insulin glargine U100 plus insulin aspart), IDegLira has been shown to be associated with similar improvements in HbA1c, with superior weight loss and reduced hypoglycemia in patients with type 2 diabetes. The present analysis evaluated the cost per patient with type 2 diabetes achieving HbA1c-focused and composite treatment targets with IDegLira and insulin glargine U100 plus insulin aspart (≤4 times daily). METHODS: The proportions of patients achieving treatment targets were obtained from the treat-to-target, non-inferiority DUAL VII study (NCT02420262). The annual cost per patient achieving target (cost of control) was analyzed from a US healthcare payer perspective. The annual cost of control was assessed for eight prespecified endpoints and four post-hoc endpoints. RESULTS: The number needed to treat to bring one patient to targets of HbA1c <7.0% and HbA1c ≤6.5% was similar with IDegLira and insulin glargine U100 plus insulin aspart. However, when weight gain and/or hypoglycemia were included, the number needed to treat was lower with IDegLira. IDegLira and insulin glargine U100 plus insulin aspart had similar costs of control for HbA1c <7.0%. However, cost of control values were substantially lower with IDegLira when the more stringent target of HbA1c ≤6.5% was used, and when patient-centered outcomes of hypoglycemia risk and impact on weight were included. CONCLUSION: IDegLira was shown to be a cost-effective treatment vs insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic targets on basal insulin in the USA.

Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials.

In individuals with type 2 diabetes, glycaemic control and cardiovascular risk factor management reduces the likelihood of late-stage diabetic complications. Guidelines recommend treatment goals targeting HbA1c, body weight, blood pressure, and low-density lipoprotein cholesterol. Development of new treatments for type 2 diabetes requires an understanding of their mechanism and efficacy, as well as their relative effects compared to other treatment choices, plus demonstration of cardiovascular safety. Subcutaneous semaglutide is a glucagon-like peptide-1 receptor agonist currently approved in several countries for once-weekly treatment of type 2 diabetes. Semaglutide works via the incretin pathway, stimulating insulin and inhibiting glucagon secretion from the pancreatic islets, leading to lower blood glucose levels. Semaglutide also decreases energy intake by reducing appetite and food cravings, and lowering relative preference for fatty, energy-dense foods. Semaglutide was evaluated in the SUSTAIN clinical trial programme in over 8000 patients across the spectrum of type 2 diabetes. This review details the efficacy and safety profile of semaglutide in the SUSTAIN 1-5 and 7 trials, and its cardiovascular safety profile in the SUSTAIN 6 trial. Semaglutide consistently demonstrated superior and sustained glycemic control and weight loss vs. all comparators evaluated. In SUSTAIN 6, involving patients at high risk of cardiovascular disease, semaglutide significantly decreased the occurrence of cardiovascular events compared with placebo/standard of care (hazard ratio 0.74, P < 0.001 for non-inferiority). Through a comprehensive phase 3 clinical trial program, we have a detailed understanding of semaglutide's efficacy, safety, cardiovascular effects and comparative role in the treatment of type 2 diabetes.

Inhaled steroids do not decrease bone mineral density but increase risk of fractures: data from the GIUMO Study Group.

Although the negative effect of systemic steroids on bone is well documented, there is not clear evidence about possible adverse effects of inhaled steroids on bone metabolism and fractures. A cross-sectional study was performed on 105 women suffering from bronchial asthma treated with inhaled steroids and 133 controls. Bone mineral density (BMD) was measured by quantitative ultrasonography (QUS) at the calcaneus and by dual X-ray absorptiometry (DXA), at both the lumbar spine and proximal femur. Patients suffering from bronchial asthma showed no statistically significant changes in BMD as measured by DXA or QUS, compared with controls. A higher prevalence of fractures was found in the group of women with bronchial asthma, with an age-adjusted odds ratio of 2.79 (95% CI: 1.19-6.54). Inhaled steroids do not appear to decrease BMD, but are associated with an increased risk of fracture in women.

Validation of PHPQoL, a Disease-Specific Quality-of-Life Questionnaire for Patients With Primary Hyperparathyroidism.

CONTEXT: Health-related quality of life (HRQoL) is impaired in primary hyperparathyroidism (PHPT) but instruments to specifically assess this are scarce. OBJECTIVE: Validate the new disease-specific Primary Hyperparathyroidism Quality of Life (PHPQoL) questionnaire in usual clinical practice. DESIGN: Observational, prospective, and multicenter. SETTING: Public hospital ambulatory care. PATIENTS: Patients with PHPT of both sexes, aged more than or equal to 18 years either initiated treatment for PHPT (group A) or had stable PHPT, not requiring therapy (group B). Patients in group A had at least one surgical criterion according to the 2009 Third International Workshop on Management of Asymptomatic PHPT. INTERVENTION: Sociodemographic, clinical, and HRQoL data (PHPQol, Short Form-36, Psychological Well-Being Index, and patients' self-perceived health status) were collected. Group A underwent 4 evaluations (baseline, 3 ± 1, 6 ± 1, and 12 ± 2 months after a therapeutic intervention) and group B 2, at baseline and 1 month later to assess test-retest reliability. RESULTS: A total of 182 patients were included (104 group A, 78 group B) with a mean age (SD) of 61.4 (12.1) years; 79.7% were women. Group A increased PHPQoL score (SD) (better HRQoL) (52 ± 23 at baseline; 62 ± 24 at 12 months; P < .001). At baseline, symptomatic patients had a lower PHPQoL score (worse) than asymptomatic ones (51 ± 21 vs 68 ± 21; P < .001). Correlations were seen between PHPQoL and Short Form-36, Psychological Well-Being Index, and self-perceived health status (P < .001). PHPQoL had good internal consistency (Cronbach's α = 0.80), test-retest reliability (group B, intraclass correlation coefficient > 0.80), and sensitivity to detect HQRoL changes over time. CONCLUSIONS: PHPQoL is a valid HRQoL measure to assess the impact of PHPT on health perception in clinical practice.

Antiresorptive therapy in hyperthyroid patients: longitudinal changes in bone and mineral metabolism.

The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism (<12 weeks) were sex and menopause stratified and randomly allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual x-ray absorptiometry in lumbar spine, femoral neck, and Ward's triangle at 0, 9, and 18 months of treatment. We also determined free T4, free T3, TSH, osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3 months of follow-up. No significant difference was observed among treatments. A euthyroid state was attained at 3 months. Bone mass increased significantly at the 9 month evaluation (P < 0.05), with a 5-10% net gain during follow-up. Nevertheless, final bone mass was 4-8% smaller than expected. Bone formation markers were increased at 0 and 3 months, with reductions at 6-9 months; resorption bone markers showed a significant reduction at the 3 month evaluation. These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6-9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.

Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin in rats after several osmotic loads.

Urinary digoxin-like immunoreactive factor (DLIF), arginine-vasopressin (AVP) and other urinary parameters were investigated under normal conditions and after the i.p. injection of the following solutions: distilled water, isotonic and hypertonic NaCl, NaHCO3, KCl and urea, at a rate of 3 ml/100 g body weight. The measurement of digoxin-like immunoreactivity by two different radioimmunoassays showed that DLIF was stimulated by all volume loads regardless of the presence or absence of osmolar compounds. This dissociation between DLIF and urinary sodium excretion suggests that DLIF may not constitute the natriuretic hormone. Moreover, a dissociation between DLIF and AVP excretion also were found, which speaks against the hypothesis of a common mechanism of stimulation for both substances.

Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status.

The objective of this study was to assess bone mineral density (BMD) and bone markers in former hyperthyroid females after long-term euthyroidism (>4 yr) following (131)I therapy, as well as the potential influence of the timing of menopause. Twenty-six females ages 57 +/- 8 yr previously diagnosed with hyperthyroidism and treated with (131)I who were euthyroid for a minimum of the last 4 yr (10 +/- 5 yr) were studied. Eighteen patients (69%) were on levothyroxine (LT(4)) replacement therapy for 9 +/- 4 yr. BMD (g/cm(2) and Z-score) was measured by dual X-ray absorptiometry in the lumbar spine, femoral neck, and Ward's triangle. BMD (Z-score) was lower than the normal reference values for the Spanish population in all sites (lumbar spine: -0.65 +/- 1.13; femoral neck: -0.47 +/- 0.95; Ward's triangle: -0.37 +/- 0.88). No differences were found between BMD values according to the etiology of the hyperthyroidism or current LT(4) therapy. Current postmenopausal patients (n = 21) showed lower BMD than current premenopausal patients in the lumbar spine and femoral neck (p < 0.05). Those women who were postmenopausal at the time of the (131)I therapy (n = 15) also had lower lumbar spine BMD than premenopausal patients (p = 0.01), while no significant difference in BMD was seen according to the menopausal status when hyperthyroidism was diagnosed. Former hyperthyroid patients after long-term euthyroidism following (131)I therapy showed reduced BMD at the lumbar spine and proximal femur. Menopausal women showed a greater reduction in bone density. The menopausal status at the time of diagnosis did not seem to have long-term effects in bone density; nevertheless, an early therapeutic intervention in premenopause is suggested to reduce bone loss.

Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment.

Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.

Effects of K+-canrenoate on the development of DOCA-salt hypertension.

The effects of K+-canrenoate, a digoxin antagonist, on the role of digoxin-like factor in the development of DOCA-salt hypertension has been examined. DOCA-salt rats treated with 66 mg kg-1 day-1 of K+-canrenoate (s.c.) presented a lower increase in blood pressure (P less than 0.01), less cardiac hypertrophy (P less than 0.05) and hypokalaemia (P less than 0.05) than non-treated DOCA-salt rats. K+-canrenoate treatment did not lead to significant changes in urinary volume, Na+ and K+ urinary excretion or suppression of plasma renin activity in DOCA-salt rats. None of the parameters were significantly different between uninephrectomized-salt rats treated or non-treated with K+-canrenoate. These data suggest a role for digoxin-like factor in DOCA-salt hypertension. However, the non-normalization of blood pressure observed in K+-canrenoate DOCA-salt treated rats indicates that other factors contribute to the initiating mechanisms in this type of hypertension. Moreover, these data suggest that digoxin-like factor plays no role in the suppression of plasma renin activity induced by DOCA and salt treatment.

[The risk factors and bone mineral density in women on long-term levothyroxine treatment]. / Factores de riesgo y densidad mineral ósea en mujeres en tratamiento prolongado con levotiroxina.

BACKGROUND: It is controversial if the long-term treatment with thyroid hormone given at substitutive or suppressive doses has a negative effect on bone metabolism. In previous reports the lack of ultrasensitive TSH assays and densitometers with adequate precision, and the heterogeneity of the patients analyzed could explain these discordant results. PATIENTS AND METHODS: We have assessed bone mineral density (BMD) in 43 premenopausal and 53 postmenopausal women, who underwent near total thyroidectomy and I-131 ablation due to differentiated thyroid cancer, that have been followed up (mean duration, 75.5 [43] months) with suppressive thyroid hormone treatment (mean dose, 170 [42] micrograms) in our hospital. Patients with history of hyperthyroidism were excluded. Lumbar BMD (L2-L4) and BMD in three different sites of hip were measured (dual X-ray densitometry) to determine the contribution of several clinical and risk factors associated with thyroid hormone therapy given to BMD. RESULTS: We have not found significant decrease in BMD at spine or hip when patients were compared with healthy, age and sex matched. Age (inverse correlation) and weight (direct correlation) were the variables mostly influencing BMD). Histologic type of thyroid neoplasia, doses of thyroid hormones, thyroid hormone levels and duration of follow-up, were not associated with changes in BMD. A decrease in calcium intake in postmenopausal and less physical activity in premenopausal women were related with a decreased lumbar BMD. CONCLUSIONS: During long-term treatment of female patients with thyroid hormones, other risk factors should be studied in order to prevent possible loss of bone mass.

[Development of a questionnaire for the assessment and quantification of overweight and obesity related lifestyles]. / Desarrollo de un cuestionario para la valoración y cuantificación de los hábitos de vida relacionados con el sobrepeso y la obesidad.

INTRODUCTION: Lifestyle intervention is mandatory for obesity treatment. The aim of this study is to design a questionnaire to describe and quantify those behaviours more closely related to obesity in the Spanish obese population. METHODS AND PROCEDURES: An expert panel designed a preliminary 57 Liker-type item questionnaire, which was self-administered to 335 overweight patients (110 male, 225 female; age, 42 +/- 14 years; BMI, 32.6 +/- 3.7 kg/m2). After a subjacent dimensionality searching and item reducing first phase, a shrunk questionnaire of 24 items was then self-administered to 156 overweight patients (52 male, 104 female; age 42 +/- 12 years; BMI, 33.1 +/- 3.5 kg/m2); 56 of those patients were re-administered the questionnaire in order to provide test-retest information. RESULTS: Final questionnaire includes 22 items clustered in five dimensions: diet caloric intake, searching for psychological well-being eating, physical activity, healthy eating and alcohol intake. Proposed factorial structure is mostly reproduced in different samples and using different extraction methods: all dimensions but alcohol intake score alpha values > 0.75 for liability; test-retest stability is greater than 0.90 in all dimensions but alcohol intake; results for all validity tests performed (of construct, of content and discriminative) are highly satisfactory. CONCLUSION: Metrics study results (liability and validity) demonstrate that the proposed questionnaire provides an excellent tool to assess those lifestyles related to obesity control.

[Decrease of the incidence of sepsis syndrome after early enteral nutrition of patients with severe burns]. / Disminución de la incidencia de síndrome séptico tras nutrición enteral precoz en grandes quemados.

The objective of this study was to evaluate the effect of early enteral nutrition on the incidence of the septic syndrome as well as its tolerance, in patients with severe burns. We retrospectively studied 64 patients older than 15 years of age, with a greater than 20% burned body surface area. They were divided into 2 groups as a function of the time elapsed between the beginning of Enteral Nutrition and the time of the burning: 23 patients were given Enteral Nutrition within 24 hours after the burn, and in 41 patients the enteral nutrition was started later than 24 hours after sustaining the thermal injury. Both groups were similar with respect to age, sex, percentage of 2nd and 3rd degree burns, incidence of inhalation, and deaths. All patients received the Enteral Nutrition through a nasogastric tube, with administration of a polymeric, hyperprotein and hypocaloric formula through a continuous infusion pump. In our study we saw a reduction of the incidence of the septic syndrome in the patients who received early enteral Nutrition (26%; 6 patients of a total of 23), with respect to those who did non receive early Enteral Nutrition (54%; 22 patients of a total of 41), with a statistical significance of p > 0.05. There were no differences between both groups with respect to the digestive tolerance to Enteral Nutrition. From our study we can deduce that early Enteral Nutrition reduces the incidence of septic complications, without this increasing the digestive intolerance to the same.

[Pharyngolaryngeal xanthomatosis: a case report]. / Xantomatosis faringolaríngea. Caso clínico.

A case occurring in a 62 year-old male with a xantomatous infiltrate taking the pharyngolarynx is reported. Basic features of xantomatosis are described as other manifestations encountered in the ENT-area.

[Mucoepidermoid carcinoma of the larynx]. / Carcinoma mucoepidermoide de laringe.

A case report of mucoepidermoid carcinoma of the larynx es presented and the literature reviewed. The inherent difficulties in histologic mucoepidermoid carcinoma is discussed. At the present time, mucoepidermoid carcinoma of the larynx should be regarded as a separate entity, its treatment based in histological grade as well as clinical behavior.

[Supraclavicular schwannoma with malignant cytologic appearance]. / Schwanoma supraclavicular con apariencia citológica de malignidad.

We present the case of a old woman with a supraclavicular mass and sarcomatous cytologic appearance. The final microscopic appearance was schwannoma. We also review the pertinent literature.