Recent Advancements in the Utilization of s-Block Organometallic Reagents in Organic Synthesis with Sustainable Solvents.

This mini-review offers a comprehensive overview of the advancements made over the last three years in utilizing highly polar s-block organometallic reagents (specifically, RLi, RNa and RMgX compounds) in organic synthesis run under bench-type reaction conditions. These conditions involve exposure to air/moisture and are carried out at room temperature, with the use of sustainable solvents as reaction media. In the examples provided, the adoption of Deep Eutectic Solvents (DESs) or even water as non-conventional and protic reaction media has not only replicated the traditional chemistry of these organometallic reagents in conventional and toxic volatile organic compounds under Schlenk-type reaction conditions (typically involving low temperatures of -78 °C to 0 °C and a protective atmosphere of N2 or Ar), but has also resulted in higher conversions and selectivities within remarkably short reaction times (measured in s/min). Furthermore, the application of the aforementioned polar organometallics under bench-type reaction conditions (at room temperature/under air) has been extended to other environmentally responsible reaction media, such as more sustainable ethereal solvents (e.g., CPME or 2-MeTHF). Notably, this innovative approach contributes to enhancing the overall sustainability of s-block-metal-mediated organic processes, thereby aligning with several key principles of Green Chemistry.

Impacto de las fracturas por fragilidad en mujeres españolas con osteoporosis posmenopáusica / Impact of fragility fractures in postmenopausal Spanish women with osteoporosis

Objetivo: dada la repercusión que tienen las fracturas por fragilidad y sus secuelas en la vida de las mujeres con osteoporosis posmenopáusica (OPM), el objetivo de este estudio es describir y analizar su impacto en esta población. Material y métodos: se realizó una encuesta a mujeres posmenopáusicas con fractura por fragilidad en un diseño observacional transversal. Se recogieron variables sociodemográficas, impacto de la fractura (necesidad de cuidados, productividad laboral), calidad de vida relacionada con la salud (CVRS, mediante cuestionario QUALEFFO-31) y disposición a pagar (DAP) por recuperarla. Resultados: participaron 120 mujeres, promedio de edad 62 ± 7 años. Las fracturas más frecuentes fueron las de radio distal (29,9 %) y las vertebrales (21,3 %). Un 53,3 % necesitó cuidados durante su recuperación (76,5 % informales; 24,9 % formales) y un 4,2 % tuvo que ingresar en un centro/residencia sociosanitaria. De aquellas que trabajaban cuando se produjo la fractura (62,5 %), el 56 % vio su vida laboral afectada (69,3 % incapacidad temporal; 17,3 % incapacidad permanente; 10,7 % reducción de jornada; 10,7 % abandono laboral; 5,3 % permiso/excedencia; 3,6 % prejubilación). El impacto de la fractura se debió principalmente al dolor (71,7 %), dificultad para realizar actividades cotidianas (48,3 %), problemas de movilidad (46,7 %) y estado emocional (41,7 %). La mayor DAP se ofreció por recuperar la capacidad para realizar actividades cotidianas y el estado emocional. La puntuación total QUALEFFO-31 (0-100) fue 49,9 ± 10,8 (función mental: 68,3 ± 7,3; dolor: 56 ± 22,6; función física: 39,3 ± 15,5). Conclusiones: las fracturas por fragilidad tienen un alto impacto en la calidad de vida de las mujeres con OPM. Resulta fundamental poner en valor aquellos aspectos que más les preocupan para optimizar su abordaje. (AU)

Objective: Given the impact of fragility fractures and their consequences on the lives of women with postmenopausal osteoporosis (PMO), the objective of this study is to describe and analyze the impact of this kind of fractures on this population. Materials and methods: A survey was conducted among postmenopausal women with fragility fractures in a cross-sectional observational design. Sociodemographic variables, fracture impact (need for care, work productivity), and data on health-related quality of life (HRQoL, assessed using the QUALEFFO-31 questionnaire), and willingness to pay (WTP) to regain HRQoL were collected. Results: A total of 120 women participated, with a mean age of 62 ± 7 years. The most frequent fractures described were distal radius fractures (29.9 %), followed by vertebral fractures (21.3 %). A total of 53.3 % required care during their recovery (76.5 %, informal; 24.9 %, formal), and 4.2 % had to be admitted to a health care or nursing home. Among those who were working when the fracture occurred (62.5 %), 56 % had their working life affected (69.3 %, temporary disability; 17.3 %, permanent disability; 10.7 %, reduced working hours; 10.7 %, quit their jobs; 5.3 %, leave of absence; and 3.6 %, early retirement). The impact of the fracture was primarily due to pain (71.7 %), difficulty performing activities of daily living (48.3 %), mobility problems (46.7 %), and emotional state (41.7 %). The highest WTP was offered to regain the ability to perform activities of daily living and improve the emotional state. The overall QUALEFFO-31 score (0-100) was 49.9 ± 10.8 (mental function, 68.3 ± 7.3; pain, 56 ± 22.6; physical function, 39.3 ± 15.5). Conclusions: Fragility fractures play a significant role on the quality of life of women with PMO. It is of paramount importance to value the aspects that concern them the most to optimize their management. (AU)

Hypocalcemia: A key biomarker in hospitalized COVID-19 patients.

BACKGROUND: At the end of 2019 a new respiratory syndrome emerged in China named Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. Considering the severity of the disease in adult subjects with one or more chronic pathologies, it was mandatory to find simple and effective biomarkers for negative prognosis of the disease easily available at the admission to the hospital. METHODS: To identify possible parameters showing association with the outcome in COVID-19 patients with pre-existing chronic diseases, blood biochemical profiles of 511 patients, enrolled from March to June 2020, were retrospectively evaluated. The pathological conditions taken into consideration were diabetes, arterial hypertension, chronic kidney disease, cardiovascular diseases, chronic obstructive pulmonary disease, obesity, and cancer. All the data were collected upon admission to the emergency room (ER) during the indicated period. RESULTS: We observed that serum and ionized calcium were prevalently altered in our cohort. We determined that hypocalcemia was a major parameter associated with mechanical ventilation and poor prognosis, correlating also with the presence of comorbidities such as cardiovascular diseases, chronic kidney disease, and cancer. In addition, we found a positive correlation between hypocalcemia and clinical complications during hospitalizations. CONCLUSIONS: Our results strengthen the relevance of serum calcium concentration as a useful prognostic biomarker in hospitalized COVID-19 patients.

Randomized clinical trial to assess the impact of oral intervention with cetylpyridinium chloride to reduce salivary SARS-CoV-2 viral load.

AIM: Aerosols released from the oral cavity help spread the SARS-CoV-2 virus. The use of a mouthwash formulated with an antiviral agent could reduce the viral load in saliva, helping to lower the spread of the virus. The aim of this study was to assess the efficacy of a mouthwash with 0.07% cetylpyridinium chloride (CPC) to reduce the viral load in the saliva of Coronavirus disease 2019 (COVID-19) patients. MATERIALS AND METHODS: In this multi-centre, single-blind, randomized, parallel group clinical trial, 80 COVID-19 patients were enrolled and randomized to two groups, namely test (n = 40) and placebo (n = 40). Saliva samples were collected at baseline and 2 h after rinsing. The samples were analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay test specific for the nucleocapsid (N) protein of SARS-CoV-2. RESULTS: With RT-qPCR, no significant differences were observed between the placebo group and the test group. However, 2 h after a single rinse, N protein concentration in saliva was significantly higher in the test group, indicating an increase in lysed virus. CONCLUSIONS: The use of 0.07% CPC mouthwash induced a significant increase in N protein detection in the saliva of COVID-19 patients. Lysis of the virus in the mouth could help reduce the transmission of SARS-CoV-2. However, more studies are required to prove this.

Spanish National Registry of Major Osteoporotic Fractures (REFRA) seen at Fracture Liaison Services (FLS): objectives and quality standards.

REFRA-FLS is a new registry in Spain aimed at identifying individuals over 50 years of age with a fragility fracture. Using this registry, we found hip fracture is the most prevalent fracture. Treatment for osteoporosis was 87.7%, with 65.3% adherence. REFRA-FLS provides fundamental data in the study of fragility fractures. PURPOSE: Fragility fractures are a growing public health concern in modern-aged societies. Fracture Liaison Services (FLS) have been shown to successfully lower rates of secondary fractures. A new registry (REFRA-FLS) has been created to monitor quality indicators of FLS units in Spain and to explore the occurrence and characteristic of fragility fractures identified by these centers. METHODS: We conducted a prospective cohort study based on fragility fractures recorded in the REFRA-FLS registry. Participants were individuals 50 years or above who suffered a low energy fragility fracture identified by the 10 participating FLS units during the study period. The type of FLS unit, the characteristics of the individuals at baseline, along with patient outcomes as quality indicators among those who completed 1 year of follow-up were analyzed. RESULTS: A total of 2965 patients and 3067 fragility fractures were identified, and the most frequent locations were hip (n = 1709, 55.7%) and spine (n = 492, 16.0%). A total of 43 refractures (4.5%) and 46 deaths (4.9%) were observed among 948 individuals in the follow-up analyses. Time from fracture to evaluation was less than 3 months in 76.7% of individuals. Osteoporosis treatment was prescribed in 87.7%, and adherence was 65.3% in Morisky-Green test. CONCLUSION: Our results provide a comprehensive picture of fragility fractures identified in FLS units from Spain. Overall, quality indicators are satisfactory although a much higher use of DXA would be desirable. As the registry grows with the incorporation of new FLS units and longer follow-up, incoming analyses will provide valuable insight.

Sulfadiazine crystalluria in a patient with lupus nephritis.

Objectives: It is estimated that 29% of patients treated with sulfadiazine ultimately develop acute kidney failure. Diagnosis is based on urine sediment analysis. Case presentation: A 71-year-old woman with loss of visual acuity in the context of a flare of systemic erythematosus lupus (SEL). A diagnosis of acute retinal necrosis was established, pending etiological confirmation. Empirical treatment with sulfadiazine was initiated. Follow-up analyses included urine sediment, which revealed pH 6, 30-50 RBCs/field, urothelial cells and lower tract epithelial cells, hyaline casts, fatty casts or Maltese cross, and abundant sulfadiazine crystals. The finding was reported to the Unit of Nephrology, and treatment was immediately suspended. Conclusions: Sulfadiazine is an antibiotic of the family of sulfamides. Crystalization of sulfadiazine in the renal tubules may cause acute interstitial nephritis. These crystals adopt different shapes according to the metabolite that crystalizes: unaltered forms precipitate into dense, globular crystals, whereas in other cases, as in the case reported in this paper, crystals adopt a fan-shaped, shocks-of-wheat morphology.

Fast Addition of s-Block Organometallic Reagents to CO2 -Derived Cyclic Carbonates at Room Temperature, Under Air, and in 2-Methyltetrahydrofuran.

Fast addition of highly polar organometallic reagents (RMgX/RLi) to cyclic carbonates (derived from CO2 as a sustainable C1 synthon) has been studied in 2-methyltetrahydrofuran as a green reaction medium or in the absence of external volatile organic solvents, at room temperature, and in the presence of air/moisture. These reaction conditions are generally forbidden with these highly reactive main-group organometallic compounds. The correct stoichiometry and nature of the polar organometallic alkylating or arylating reagent allows straightforward synthesis of: highly substituted tertiary alcohols, ß-hydroxy esters, or symmetric ketones, working always under air and at room temperature. Finally, an unprecedented one-pot/two-step hybrid protocol is developed through combination of an Al-catalyzed cycloaddition of CO2 and propylene oxide with the concomitant fast addition of RLi reagents to the in situ and transiently formed cyclic carbonate, thus allowing indirect conversion of CO2 into the desired highly substituted tertiary alcohols without need for isolation or purification of any reaction intermediates.

Patients receiving a high burden of antibiotics in the community in Spain: a cross-sectional study.

Some patients in the community receive a high burden of antibiotics. We aimed at describing the characteristics of these patients, antibiotics used, and conditions for which they received antibiotics. We carried out a cross-sectional study. Setting: Thirty Health Primary Care Areas from 12 regions in Spain, covering 5,960,191 inhabitants. Patients having at least 30 packages of antibacterials for systemic use dispensed in 2017 were considered. Main outcome measures: Prevalence of antibiotic use, conditions for which antibiotics were prescribed, clinical characteristics of patients, comorbidities, concomitant treatments, and microbiological isolates. Patient's average age was 70 years; 52% were men; 60% smokers/ex-smokers; 54% obese. Overall, 93% of patients had, at least, one chronic condition, and four comorbidities on average. Most common comorbidities were cardiovascular and/or hypertension (67%), respiratory diseases (62%), neurological/mental conditions (32%), diabetes (23%), and urological diseases (21%); 29% were immunosuppressed, 10% were dead at the time of data collection. Patients received three antibiotic treatments per year, mainly fluoroquinolones (28%), macrolides (21%), penicillins (19%), or cephalosporins (12%). Most frequently treated conditions were lower respiratory tract (infections or prophylaxis) (48%), urinary (27%), and skin/soft tissue infections (11%). Thirty-five percent have been guided by a microbiological diagnosis, being Pseudomonas aeruginosa (30%) and Escherichia coli (16%) the most frequent isolates. In conclusion, high antibiotic consumers in the community were basically elder, with multimorbidity and polymedication. They frequently received broad-spectrum antibiotics for long periods of time. The approach to infections in high consumers should be differentiated from healthy patients receiving antibiotics occasionally.

Sleep characteristics in health workers exposed to the COVID-19 pandemic.

INTRODUCTION: The development of sleep disorders, and specifically insomnia, has been linked to the exposure to different stressors. In this line, Coronavirus disease 2019 (COVID-19) outbreak caused by the new coronavirus SARS-CoV-2, has caused a huge impact on our environment, and has exposed healthcare workers to an unprecedented threat. In this study, we try to assess sleep quality and the development of sleep disorders in health personnel directly dedicated to the care of COVID-19 patients at the height of the pandemic, compared to the general population. MATERIALS AND METHODS: A cross-sectional, anonymized, self-reported questionnaire survey was carried out at the "12 de Octubre" Hospital, in Madrid, Spain, during the outbreak of COVID-19, from March 1st to April 30th 2020. We compared two groups, healthcare workers who have treated directly COVID-19 patients versus non-healthcare workers. The questionnaire included demographic data, sleep related aspects, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and 17-items Hamilton Rating Scale (HRS). RESULTS: In total 170 participants completed the questionnaire successfully, 100 healthcare workers and 70 non-healthcare workers. Self-reported insomnia, nightmares, sleepwalking, sleep terrors and PSQI>6 were more frequent in the healthcare group (p < 0,05). Shift work was associated to greater risk when performing multiple logistic regression analysis. CONCLUSIONS: We observed that, during the outbreak of COVID-19, healthcare workers on the front line developed more sleep disturbances than non-healthcare professionals, and they had worse quality of sleep. Special attention should be paid to shift workers. Concrete protection and prevention measures for particularly exposed population should be considered in pandemic situations.

Combination of organocatalytic oxidation of alcohols and organolithium chemistry (RLi) in aqueous media, at room temperature and under aerobic conditions.

A tandem protocol to access tertiary alcohols has been developed which combines the organocatalytic oxidation of secondary alcohols to ketones followed by their chemoselective addition by several RLi reagents. Reactions take place at room temperature, under air and in aqueous solutions, a trio of conditions that are typically forbidden in polar organometallic chemistry.

DESign of Sustainable One-Pot Chemoenzymatic Organic Transformations in Deep Eutectic Solvents for the Synthesis of 1,2-Disubstituted Aromatic Olefins.

The self-assembly of styrene-type olefins into the corresponding stilbenes was conveniently performed in the Deep Eutectic Solvent (DES) mixture 1ChCl/2Gly under air and in the absence of hazardous organic co-solvents using a one-pot chemo-biocatalytic route. Here, an enzymatic decarboxylation of p-hydroxycinnamic acids sequentially followed by a ruthenium-catalyzed metathesis of olefins has been investigated in DES. Moreover, and to extend the design of chemoenzymatic processes in DESs, we also coupled the aforementioned enzymatic decarboxylation reaction to now concomitant Pd-catalyzed Heck-type C-C coupling to produce biaryl derivatives under environmentally friendly reaction conditions.

Eficacia y seguridad del tratamiento quirúrgico en la cefalea en racimos / Efficacy and safety of surgical treatment of cluster headache

ANTECEDENTES Y OBJETIVO: La cefalea en racimos (CR) es la cefalea humana más grave y se cronifica en un 10-20% de los pacientes, pudiendo llegar a ser refractaria a todos los fármacos eficaces en un 10% de ellos. En este escenario se indican procedimientos quirúrgicos: radiofrecuencias del ganglio esfenopalatino ipsilateral al dolor (RF-GEFP), estimulación bilateral de los nervios occipitales (E-NOM) y estimulación cerebral profunda (ECP) del hipotálamo posteroinferior ipsilateral. Se ha analizado específicamente la eficacia y seguridad de cada una de ellas, pero no se ha descrito la evolución de una serie de pacientes siguiendo este itinerario quirúrgico por orden de agresividad. PACIENTES: Pacientes con CR crónica y refractaria según los criterios de la European Headache Federation. Fueron sometidos secuencialmente a RF-GEFP, E-NOM si ineficacia del anterior y ECP si ineficacia del anterior. RESULTADOS: Incluimos prospectivamente a 44 pacientes entre noviembre de 2003 y junio de 2018 con una edad media de 38,3 años siendo el 70% hombres. El seguimiento medio fue de 87,4 meses. Respondieron a 74 procedimientos de RF-GEFP 19 pacientes (33,3%). De los 25 restantes, se implantó un dispositivo de E-NOM en 22 de ellos, mostrando una eficacia del 50%. Finalmente, se sometieron a ECP del hipotálamo posteroinferior ipsilateral 9 pacientes con una eficacia del 88,8%. No se constataron complicaciones graves en ninguno de los 3 procedimientos. CONCLUSIONES: La aplicación secuencial de los 3 procedimientos quirúrgicos logró revertir la grave situación de CR crónica y refractaria a una CR episódica en el 93% de los pacientes con una morbilidad quirúrgica aceptable

BACKGROUND AND OBJECTIVES: Cluster headache (CR) is the most severe human headache and is chronic in 10%-20% of patients, and 10% can become refractory to all effective drugs. In this scenario, surgical procedures are indicated: radiofrequencies of the sphenopalatine ganglion ipsilateral to pain (RF-SPG), bilateral stimulation of the occipital nerves (NOM-S) and deep brain stimulation (DBS) of the ipsilateral posterior hypothalamus. The efficacy and safety of each of these procedures has been specifically analyzed, but the progress of a series of patients following this surgical route in order of aggressiveness has not been described. PATIENTS: Patients with chronic and refractory CR according to the criteria of the European Headache Federation. The patients underwent RF-SPG, NOM-S sequentially if the previous procedure had been ineffective, and DBS if the previous procedure had been ineffective. RESULTS: We prospectively included 44 patients between November 2003 and June 2018 with an average age of 38.3 years; 70% were men. The mean follow-up was 87.4 months. Nineteen patients responded to 74 procedures of RF-SPG (33.3%). Of the remaining 25 patients, a NOM-S device was implanted in 22, showing an efficacy of 50%. Finally, 9 patients underwent ECP of the ipsilateral lower-posterior hypothalamus with an efficacy of 88.8%. No serious complications were found following any of these 3 procedures. CONCLUSIONS: The sequential application of these three surgical procedures succeeded in reversing the serious situation of chronic CR refractory to an episodic CR in 93% of patients with acceptable surgical morbidity

Long term effects on biochemical bone markers of a single infusion of zoledronic acid in Paget disease of bone.

BACKGROUND: The aim of the present study is to evaluate long term biochemical response to a single dose of zoledronic acid in patients with Paget disease of bone, as well as evaluating the value of bone turnover markers in diagnosis and follow-up. METHODS: This is an observational, descriptive and prospective study. Included patients received a single-dose intravenous infusion of 5 mg zoledronic acid. Bone turnover markers were measured at baseline, and in every follow up visit. RESULTS: Thirty-nine patients with a mean follow-up of 56.49 months were included. At the time Paget disease was diagnosed, all of the patients (100%) had high serum procollagen type 1 amino-terminal propeptide values, but not all patients had high serum C-terminal telopeptide and alkaline phosphatase values (85% and 89% respectively). Biochemical response to therapy occurred in 38 out of 39 patients (97%). Two patients had partial response at 6 months but complete response thereafter. Only one patient relapsed (nadir procollagen type 1 amino-terminal propeptide 35.06 µg/l, value at relapse 75.2 µg/l) 4.5 years after treatment. Values of serum C-terminal telopeptide and alkaline phosphatase of this patient were normal despite P1NP relapse. CONCLUSIONS: We hence conclude that zoledronic acid is effective in inducing and maintaining biochemical remission and that procollagen type 1 amino-terminal propeptide is a better diagnostic and prognostic marker in PDB when compared to C-terminal telopeptide and alkaline phosphatase.

CYFRA 21-1 in patients with suspected cancer: evaluation of an optimal cutoff to assess the diagnostic efficacy and prognostic value.

Objectives: Chosen cutoff for cytokeratin 19 fragment antigen (CYFRA 21-1) as a tumor biomarker considerably influences its diagnostic and prognostic usefulness. The aim of the present study is to determine an optimal cutoff value for diagnostic validity of CYFRA 21-1 by Lumipulse ® technology in patients with suspected cancer and also to determine if CYFRA 21-1 levels provide prognostic value. Methods: A consecutive 284 patients suggestive of malignant disease from six hospitals of Madrid were enrolled in a retrospective design. Optimal CYFRA 21-1 cutoff value was obtained by receiver operating characteristic curve and Youden test. The diagnostic validity was evaluated according to sensitivity, specificity, predictive values and likelihood ratios. The prognostic value of CYFRA 21-1 was checked using multiple logistic regression. Thirty-two diagnostic cancers were confirmed. Results: The most optimal cutoff was 3.15 ng/mL. This cutoff showed a better specificity 93.63% (95% confidence interval [CI], 89.66-96.16), positive predictive value 60.98% (95% CI, 44.54-75.38) and positive likelihood ratio 12.65 (95% CI, 7.64-20.95) than the cutoff recommended by Fujirebio® (1.8 ng/mL) (specificity: 73.71% [95% CI, 67.72-78.95], positive predictive value: 29.79% [95% CI, 21.02-40.23] and positive likelihood ratio 3.43 [95% CI, 2.71-4.35]), improving the current diagnostic accuracy. In multivariate analysis, elevated levels of CYFRA 21-1 (>3.15 ng/mL) was confirmed as an unfavorable prognostic factor. Conclusions: The best cutoff for CYFRA 21-1 obtained was 3.15 ng/mL in patients with suspected cancer. This new cutoff decreases the false positive rate and improves the diagnostic efficacy of CYFRA 21-1 as a tumor marker as well as its association with death events.

Efficacy and safety of surgical treatment of cluster headache. / Eficacia y seguridad del tratamiento quirúrgico en la cefalea en racimos.

BACKGROUND AND OBJECTIVES: Cluster headache (CR) is the most severe human headache and is chronic in 10%-20% of patients, and 10% can become refractory to all effective drugs. In this scenario, surgical procedures are indicated: radiofrequencies of the sphenopalatine ganglion ipsilateral to pain (RF-SPG), bilateral stimulation of the occipital nerves (NOM-S) and deep brain stimulation (DBS) of the ipsilateral posterior hypothalamus. The efficacy and safety of each of these procedures has been specifically analyzed, but the progress of a series of patients following this surgical route in order of aggressiveness has not been described. PATIENTS: Patients with chronic and refractory CR according to the criteria of the European Headache Federation. The patients underwent RF-SPG, NOM-S sequentially if the previous procedure had been ineffective, and DBS if the previous procedure had been ineffective. RESULTS: We prospectively included 44 patients between November 2003 and June 2018 with an average age of 38.3 years; 70% were men. The mean follow-up was 87.4 months. Nineteen patients responded to 74 procedures of RF-SPG (33.3%). Of the remaining 25 patients, a NOM-S device was implanted in 22, showing an efficacy of 50%. Finally, 9 patients underwent ECP of the ipsilateral lower-posterior hypothalamus with an efficacy of 88.8%. No serious complications were found following any of these 3 procedures. CONCLUSIONS: The sequential application of these three surgical procedures succeeded in reversing the serious situation of chronic CR refractory to an episodic CR in 93% of patients with acceptable surgical morbidity.

The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment.

Several antiresorptive drugs, like bisphosphonates and denosumab, are currently available for the treatment of osteoporosis due to their evidenced efficacy in reducing fracture risk at mid-term. Osteoanabolic therapies, like teriparatide, whose treatment duration is limited to 2 years, have also shown efficacy in the reduction of fracture risk. However, depending on the severity of osteoporosis and the presence of other associated risk factors for fracture, some patients may require long-term treatment to preserve optimal bone strength and minimize bone fracture risk. Given the limited duration of some treatments, the fact that most of the antiresorptive drugs have not been assessed beyond 10 years, and the known long-term safety issues of these drugs, including atypical femoral fractures or osteonecrosis of the jaw, the long-term management of these patients may require an approach based on drug discontinuation and/or switching. In this regard, interest in sequential osteoporosis therapy, wherein drugs are initiated and discontinued over time, has grown in recent years, although the establishment of an optimal and individualized order of therapies remains controversial. This review reports the currently available clinical evidence on the discontinuation effects of different anti-osteoporotic drugs, as well as the clinical outcomes of the different sequential treatment regimens. The objective of this article is to present up-to-date practical knowledge on this area in order to provide guidance to the clinicians involved in the management of patients with osteoporosis.

Prevention of canine ocular thelaziosis (Thelazia callipaeda) with a combination of milbemycin oxime and afoxolaner (Nexgard Spectra®) in endemic areas in France and Spain.

In the past decade, canine thelaziosis due to Thelazia callipaeda has been diagnosed in an increasing number of European countries, with endemic areas being identified. A multi-center field trial was conducted in endemic areas in France and Spain to evaluate the efficacy of monthly administrations of the oral milbemycin oxime/afoxolaner combination (NexGard Spectra®) for the prevention of T. callipaeda infection in at-risk dogs. A total of 79 dogs negative for T. callipaeda and with a clinical history of eyeworm infection in the past two years completed the study. Dogs were randomly allocated either to a negative control group (42 dogs) or to the NexGard Spectra® treated group (37 dogs). All dogs were followed up for a 6-month period and assessed monthly for the presence of nematodes on the eyes and for the signs of ocular thelaziosis (e.g., conjunctivitis, keratitis, and ocular discharge). When the presence of nematodes was confirmed, the conjunctival fornix was flushed with a saline solution for parasite recovery and counting, and the dogs were treated appropriately. Recovered parasites were stored in 70% alcohol for subsequent morphological identification. During the course of the study, 57.1% (24/42) of the control dogs were diagnosed positive for Thelazia infection, which illustrates a high incidence rate of parasite infection. Conversely, no eyeworm was recovered from any of the 37 dogs that received NexGard Spectra®. All parasites sampled were confirmed to be T. callipaeda. This clinical field study demonstrated that monthly administrations of NexGard Spectra® provided 100% preventive efficacy against canine thelaziosis.

[Not Available]. / Diagnóstico y tratamiento del hábito tabáquico en pacientes con EPOC. Estudio ADEPOCLE.

Introducción: estimar la prevalencia del tabaquismo y analizar cómo se diagnostican y se trata a los fumadores diagnosticados de EPOC.Métodos: estudio epidemiológico, transversal, multicéntrico (30 centros salud de la provincia de León). Incluyó pacientes mayores de 35 años diagnosticados y tratados de EPOC. Variables analizadas: edad, sexo, hábitat, datos antropométricos, tabaquismo, número de paquetes/año, cooximetría, dependencia (escala analógico-visual), motivación (test de Fagerström), autoeficacia, estado anímico, intentos previos, terapia cognitivo-conductual, tratamiento farmacológico (TSN, bupropión, vareniclina) y recaídas. Los resultados se expresan con sus IC al 95,5%.Resultados: se incluyó a 833 pacientes, el 85,8% varones, edad media: 64,69 (53,66-75,61) años y 20,65 (4,47-36,8) años de evolución de la EPOC. El 86,67% (80,30-93,30) tenían antecedentes de tabaquismo (n = 722), de 35,26 (17,87-52,64) años de evolución, con consumo medio 28,36 (9,60-46,86) paquetes año, p < 0,001, siendo el 58% fumadores severos. El 57,4% (53,90-60,60) son exfumadores. El 29,3% (26,40-32,70) fumadores activos declarados vs. 35,11% (33,90-37,12) fumadores diagnosticados por cooximetría p < 0,05. Los 288 fumadores activos, presentaban baja motivación (49,80%), alta dependencia (49,5%), actitud negativa (52,60%), bajo estado de ánimo (32,05%), con 2,72 (1,74-3,67) intentos para dejar de fumar, p < 0,0001. La terapia conductivo-conductual (TCC) combinado con tratamiento farmacológico se realizó en el 55,8% (52,2-54,9), p < 0,05; La intervención más efectiva fue TCC combinada con vareniclina logrando una abstinencia del 29,86%. En total dejaron de fumar un 51,05% (49,49-52,70) de los pacientes con EPOC, p < 0,001.Conclusiones: la prevalencia de tabaquismo en la EPOC en nuestro medio continúa siendo inadmisiblemente elevada. Es necesaria una mayor implicación para disminuir su impacto en la salud de estos pacientes.

Diagnóstico y tratamiento del hábito tabáquico en pacientes con enfermedad pulmonar obstructiva crónica. Estudio ADEPOCLE / Diagnosis and treatment of smoking in patients with chronic obstructive pulmonary disease. ADEPOCLE study

Introducción y objetivos: El tabaco es la principal causa de enfermedad pulmonar obstructiva crónica (EPOC). El objetivo de este estudio es estimar la prevalencia del tabaquismo y analizar cómo se diagnostican y se trata a los fumadores diagnosticados de EPOC. Métodos: estudio epidemiológico, transversal, multicéntrico (30 centros salud de la provincia de León). Incluyó pacientes mayores de 35 años diagnosticados y tratados de EPOC. Variables analizadas: edad, sexo, hábitat, datos antropométricos, tabaquismo, número de paquetes/año, cooximetría, dependencia (escala analógico-visual), motivación (test de Fagerström), autoefi cacia, estado anímico, intentos previos, terapia cognitivo-conductual, tratamiento farmacológico (TSN, bupropión, vareniclina) y recaídas. Los resultados se expresan con sus IC al 95,5%. Resultados: se incluyó a 833 pacientes, el 85,8% varones, edad media: 64,69 (53,66-75,61) años y 20,65 (4,47-36,8) años de evolución de la EPOC. El 86,67% (80,30-93,30) tenían antecedentes de tabaquismo (n = 722), de 35,26 (17,87-52,64) años de evolución, con consumo medio 28,36 (9,60-46,86) paquetes año, p < 0,001, siendo el 58% fumadores severos. El 57,4% (53,90-60,60) son exfumadores. El 29,3% (26,40-32,70) fumadores activos declarados vs. 35,11% (33,90-37,12) fumadores diagnosticados por cooximetría p < 0,05. Los 288 fumadores activos, presentaban baja motivación (49,80%), alta dependencia (49,5%), actitud negativa (52,60%), bajo estado de ánimo (32,05%), con ,72 (1,74-3,67) intentos para dejar de fumar, p < 0,0001. La terapia conductivo-conductual (TCC) combinado con tratamiento farmacológico se realizó en el 55,8% (52,2-54,9), p < 0,05; La intervención más efectiva fue TCC combinada con vareniclina logrando una abstinencia del 29,86%. En total dejaron de fumar un 51,05% (49,49-52,70) de los pacientes con EPOC, p < 0,001. Conclusiones: la prevalencia de tabaquismo en la EPOC en nuestro medio continúa siendo inadmisiblemente elevada. Es necesaria una mayor implicación para disminuir su impacto en la salud de estos pacientes (AU)

Background and objectives: Smoking is the main cause of chronic obstructive pulmonary disease (COPD). The objective of this study is to estimate the prevalence of smoking and analyze how the COPD smokers are diagnosed and treated. Methods: Multicenter, epidemiological, transversal study (30 health centers in the province of Leon, Spain). It included patients over 35 years old diagnosed and treated for COPD. The analyzed variables are: age, sex, habitat, anthropometric data, smoking, pack-years cooximetry, dependence (analog-visual scale), motivation (Fagerström test), self-effi cacy, mood, previous attempts, cognitive behavioral therapy, pharmacotherapy (NRT, bupropion, varenicline) and relapses. Results are expressed with CI 95.5%. Results: 833 patients were included. 85.8% males; mean age: 64.69 (53.66-75.61) years and 20.65 (4.47-36.8) years of COPD evolution. The 86.67% (80.30-93.30) had previous history of tabaquism (n = 722) with 35.26 (17.87-52.64) years of evolution and an average consumption of 28.36 (9.60-46.86) packs per year p < 0.001, 58% being heavy smokers. 57.4% (53.90-60.60) are former smokers. 29.3% (26.40-32.70) Smoking declared assets vs. 35.11% (33.90-37.12) smokers diagnosed by cooximetry p < 0.05. 288 active smokers had low motivation (49.80%), high dependence (49.5%), negative attitude (52.60%), low mood (32.05%), with 2.72 (1.74-3.67) attempts to quit smoking, p < 0.0001. The conductive-behavioral therapy (CBT) combined with drug treatment was performed in 55.8% (52.2 to 54.9), p < 0.05; the most effective intervention was CBT combined with varenicline achieving an abstinence of 29.86%. A total of 51.05% (49.49 to 52.70) out of the patients with COPD stopped smoking, p < 0.001. Conclusions: The prevalence of smoking in COPD in our environment remains unacceptably high. Greater involvement is required to reduce its impact on the health of these patients (AU)

Vacaciones terapéuticas en osteoporosis: estrategia en el tratamiento a largo plazo con bifosfonatos / Therapeutic holidays in osteoporosis: long-term strategy of treatment with bisphosphonates

Los bifosfonatos (BF) orales son fármacos ampliamente utilizados en el tratamiento de la osteoporosis y se sitúan como primera línea de tratamiento para la osteoporosis en la mayoría de las guías clínicas. Son fármacos eficaces que reducen la aparición de fracturas e incluso disminuyen la mortalidad. Debido a su gran afinidad por el tejido óseo, los BF han demostrado que, incluso cuando se interrumpe su administración, siguen ofreciendo un efecto protector sobre la densidad mineral ósea e incluso sobre la aparición de nuevas fracturas. Sin embargo, su uso prolongado durante años se ha relacionado con la aparición de algunas complicaciones, como la osteonecrosis mandibular o las fracturas atípicas de fémur, que han cuestionado la duración del tratamiento con estos fármacos y abierto la posibilidad de realizar interrupciones, definitivas o temporales, reconocidas como «vacaciones terapéuticas». Así, en pacientes tratados con BF durante un período de 3 a 5 años con riesgo bajo de fractura, se aconseja retirar el fármaco y reiniciarlo cuando vuelva a presentar indicación de tratamiento. En cambio, en pacientes con riesgo moderado, se aconseja realizar vacaciones terapéuticas y reevaluar a los 2-3 años para reiniciar el tratamiento. Por el contrario, en aquellos pacientes con riesgo elevado de fractura no debería retirarse el tratamiento (AU)

Oral bisphosphonates (BF) are drugs widely used in the treatment of osteoporosis and placed as first-line treatment for osteoporosis in most clinical guidelines. BF are effective drugs that reduce the incidence of fractures and even reduce mortality. Because of their great affinity for bone, BF have shown that even when they are discontinued still offer a latent protective effect on bone mineral density, maintaining their anti-fracture effect. However, prolonged use for years has been linked to the gradual emergence of complications such as osteonecrosis of the jaw or atypical femur fractures, which have raised questions as when to hold and when to make a final or temporary break, recognized as periods of rest or 'therapeutic holidays' of these drugs. Thus, in patients treated with BF for a period of 3-5 years with a low risk of fracture, the drug should be discontinued and restarted when there is an indication for treatment. In contrast, in patients with moderate risk, therapeutic holidays are advised, while reassessing after 2-3 years for restarting purposes. Finally, in patients with high risk of fracture, treatment with BF should not be withdra (AU)