Fundamental limits in structured principal component analysis and how to reach them.

How do statistical dependencies in measurement noise influence high-dimensional inference? To answer this, we study the paradigmatic spiked matrix model of principal components analysis (PCA), where a rank-one matrix is corrupted by additive noise. We go beyond the usual independence assumption on the noise entries, by drawing the noise from a low-order polynomial orthogonal matrix ensemble. The resulting noise correlations make the setting relevant for applications but analytically challenging. We provide characterization of the Bayes optimal limits of inference in this model. If the spike is rotation invariant, we show that standard spectral PCA is optimal. However, for more general priors, both PCA and the existing approximate message-passing algorithm (AMP) fall short of achieving the information-theoretic limits, which we compute using the replica method from statistical physics. We thus propose an AMP, inspired by the theory of adaptive Thouless-Anderson-Palmer equations, which is empirically observed to saturate the conjectured theoretical limit. This AMP comes with a rigorous state evolution analysis tracking its performance. Although we focus on specific noise distributions, our methodology can be generalized to a wide class of trace matrix ensembles at the cost of more involved expressions. Finally, despite the seemingly strong assumption of rotation-invariant noise, our theory empirically predicts algorithmic performance on real data, pointing at strong universality properties.

Pain reduction of topical sevoflurane vs intravenous opioids in pressure ulcers.

Recently, it has been reported that topical irrigations of liquid sevoflurane on the bed of painful wounds produce a rapid, intense, and lasting analgesic effect. In this paper, A cohort of 112 patients with painful pressure ulcers who were refractory to opioids (or who exhibited undesirable adverse events to them) was treated with topical sevoflurane as per local institutional policy. These patients were recruited from an intensive care unit for a period of 3 years. The main aim was to determine the effectiveness of topical sevoflurane in reducing the pain of PUs and reducing the ulcer area. Study findings are reported and discussed herein and suggest that sevoflurane is a viable and promising treatment option for PUs.

Occupational exposure to sevoflurane following topical application to painful wounds.

BACKGROUND: Occupational exposure to halogenated anesthetics employed for general anesthesia has been extensively studied. Conversely, a new modality of treatment of painful wounds with topical sevoflurane lacks exposure studies. OBJECTIVES: To evaluate the magnitude of acute occupational exposure to sevoflurane following topical application to painful wounds. METHODS: Four patients with chronic painful wounds were treated with topical sevoflurane (20, 20, 20 and 10 mL) following an approved therapeutic protocol in our Pain Management Unit. Eight passive dosimeters were placed at different locations of a treatment room with a volume of 163 m3 and 3.3 air changes per hour: 3 for near peak (for 20-50 min) and 1 overall exposure (for 3.4 h) at the nurse's breathing zone, and 4 for area exposure (for 3-3.4 h). Worst-case scenario theoretical concentrations of sevoflurane were also calculated. RESULTS: The highest levels were obtained for two dosimeters worn by the nurse at the breathing zone (8.28 and 9.12 ppm-TWA [parts per million-Time-Weighted Average]), while the lowest level was obtained from the dosimeter placed on the most distant wall from patients (0.73 ppm-TWA). Theoretical concentrations were calculated from standard volatilization principles and were in agreement with the concentrations measured. Discussion-Conclusions: All air concentrations measured were lower than exposure limits set by occupational safety agencies from Finland, Sweden and Norway, which range from 10 ppm for a TWA of 8 hours to 20 ppm for short-term exposures (15 min). Application of topical sevoflurane on wounds seems to be environmentally safe for health-care professionals as it produces exposure levels lower than the established limits for anesthetic procedures.

Chronic outpatient treatment with topical sevoflurane in patients with vascular ulcers. / Tratamiento crónico ambulatorio con sevoflurano tópico en pacientes con úlceras vasculares.

OBJECTIVE: To show the effectiveness and safety of topical sevoflurane after ambulatory and prolonged administration in patients with refractory vascular ulcers. METHODS: Retrospective observational study analyzing clinical improvement and vascular ulcers surface area variation after topical application of sevoflurane. Inclusion criteria were patients with painful vascular ulcers refractory to usual therapies and who were treated with topical sevoflurane for at least 36 months. The following variables were collected: age, sex, medical history, associated comorbidity, ulcer etiology and medical treatment. The visual analog scale was used to measure baseline and break through pain intensity before and after treatment. RESULTS: Nine patients met the inclusion criteria of the total number of patients treated whose median age was 74.8 ± 7.5 years. Cases 2 and 9 died during follow-up. In all cases, the analgesic action of topical sevoflurane was rapid (3.1 ± 2.1 minutes), intense (visual analog scale: 7 ± 1.1 to 1.4 ± 1.1 points) and long-lasting (6 to 24 h). With the exception of case 4, all patients experienced a large reduction in vascular ulcers surface area (15.1 ± 5.0 a 2.7 ± 4.2) and tolerance was not observed over time. CONCLUSION: Topical application of sevoflurane is an analgesic and re-epithelializing strategy for vascular ulcers with a successful safety profile.

Safe administration of noradrenaline by the peripheral route: A systematic review. / Administración segura de noradrenalina por vía periférica: una revisión sistemática.

PURPOSE: To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

[Translated article] Safe administration of noradrenaline by the peripheral route: A systematic review.

PURPOSE: To review and analyse the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS, and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischaemia, and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Pituitary Abscess: A General Retrospective Diagnosis.

We present the case of a 27-year-old female who had a history of recurrent headaches and visual disturbances. Magnetic resonance imaging of the brain showed a lesion that suggested pituitary adenoma, with indications of a recent bleeding or cystic degeneration. Nonhormonal deficiencies were documented, restricted to nontumoral hyperprolactinemia. Transsphenoidal approach surgery was performed and the purulent material was drained, confirming the diagnosis of pituitary abscess. Sinusitis was considered to be the only possible cause of this condition. Empirical treatment to Gram-positive anaerobic cocci was administrated, with a satisfactory response.

Non-Invasive Biochemical Testing of ACTH-dependent Cushing's Disease: Do We Still Need Petrosal Sinus Sampling?

Differentiating between a pituitary from an ectopic source of ACTH could be a real one of the major challenges of clinical endocrinology. The Bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold standard for identifying the source of ACTH; however, is not available worldwide. After the SARS-CoV-2 pandemic, algorithms that include biochemical and imaging tests have gained importance as an alternative to BIPSS. This review summarizes the drawbacks in the differential diagnosis of ACTH-dependent Cushing; the evolution of diagnostic tests, and the evidence that exists on their performance. As well as a comparison between the advantages and disadvantages of invasive and non-invasive tests.

First Report on the Genetic Diversity of Populations of Gossypium barbadense L. and Gossypium hirsutun L. in the Amazonian Native Communities, Cusco-Peru.

The genus Gossypium has important ethnobotanical and economic value for Amazonian Native Communities (A.N.C.). However, little research has been undertaken on the distribution and genetic diversity of cotton populations maintained in the Peruvian rainforest. This work aims to present the first report on the genetic diversity of Gossypium spp. populations in the A.N.C. of the province of La Convención, Cusco-Peru. The methodology was based on exploring, collecting, identifying, and characterizing the Gossypium populations present in the A.N.C. Twenty-six descriptors were evaluated (9 quantitative and 17 qualitative), and with this information, distribution, correlation, and principal component (PC) analyses were carried out. As a result, plants of two species [G. barbadense L. (44 samples) and G. hirsutum L. (19 samples)], one variety [G. barbadense var. brasiliensis (75 samples)], and three previously unidentified variations (9 samples) were identified. Altogether, 147 samples were collected. G. barbadense var. brasiliensis, which was always found in association with other economic crops within an altitude range of 338 to 1086 m, was the most predominant (51%), distributed in eleven A.N.C. and always in small plots (up to 2 ha). G. barbadense L. was cultivated between 397 and 1137 m of altitude in eight A.N.C. in plots of up to 3 ha in marginal lands. G. hirsutum L., with a smaller distribution (13%), was found between 334 and 497 m of altitude in only three communities; this species is cultivated in marginal areas throughout the year. The variability found for the first two PCs when considering the quantitative and qualitative descriptors was high (74.7%) and moderate (48.2%), respectively. When combining all the descriptors, the analysis showed that the first two PCs accounted for 51.8% of the total variability of the data. The PCs of the two types of data and their combination confirmed that the three populations found were grouped. The nine undefined samples were close to or intermediate between the described ones, showing that these samples may be the result of spontaneous crosses; as such, these samples need to be better evaluated with other tools for further definition. The information obtained shows that in the A.N.C. of Cusco-Peru, there is variability conserved by the inhabitants, who have been able to maintain and use these genotypes, even from their Amazonian indigenous ancestry, and the environment has been able to generate variability among the species, as will be highlighted in future works.

Hirsutism and Polycystic Ovarian Morphology are the Most Frequent Components of Polycystic Ovary Syndrome in Women with Type 1 Diabetes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown. AIM: To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS. METHODS: A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS. RESULTS: Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm3, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively. CONCLUSION: PCOS is a very heterogeneous entity, with a high frequency in women with T1D.

Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

Metformin in Differentiated Thyroid Cancer: Molecular Pathways and Its Clinical Implications.

Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis. Aside being the first-line therapy for Type 2 Diabetes (T2D), many pleiotropic effects have been discovered in recent years, such as its capacity to reduce cancer risk and tumorigenesis. Although widely studied, the effect of metformin on thyroid cancer remains controversial. Potential mechanisms for its growth inhibitory effects have been elucidated in various preclinical studies that involved pathways related to adenosine mono-phosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), mitochondrial glycerophosphate dehydrogenase (mGPDH), and the nuclear factor κB (NF-κB). Hyperinsulinemia increases cell glucose uptake and oxidative stress, and promotes thyroid cell growth, leading to hyperproliferation, carcinogenesis, and the development of malignant tumors. Furthermore, it has also been related to thyroid nodules size in nodular disease, as well as tumoral size in patients with thyroid cancer. Several clinical studies concluded that metformin might have an important role as an adjuvant therapy to reduce the growth of benign and malignant thyroid neoplasms. This suggests that metformin might be useful for patients with differentiated or poorly differentiated thyroid cancer and metabolic diseases such as insulin resistance or diabetes.

[Proinflammatory cytokines in polycystic ovarian syndrome]. / Citocinas proinflamatorias en el síndrome de ovario poliquístico.

During folliculogenesis, different proinflammatory cytokines have a physiological role in the weakening of the follicle wall and an eventual rupture at ovulation. Chronic inflammation is closely related to endothelial dysfunction, cardiovascular disease, coronary artery disease, and polycystic ovary syndrome. Polycystic ovary syndrome is characterized by androgen excess and ovarian dysfunction. Emerging evidence suggests that the long-term metabolic effects and cardiovascular complications observed in this syndrome may be related to the presence of a mild chronic inflammatory state. It is unclear whether androgen excess promotes an inflammatory state or, conversely, whether inflammatory molecules stimulate androgen production. Early detection of risk factors will help in the prevention and control of cardiovascular diseases, since the metabolic alterations associated with this syndrome can predispose to worse cardiovascular health outcomes.

Diferentes citocinas proinflamatorias producidas durante la foliculogénesis tienen un rol fisiológico en el debilitamiento de la pared del folículo y la eventual ruptura en la ovulación. La inflamación crónica está relacionada de forma muy cercana con disfunción endotelial, enfermedad cardiovascular, enfermedad arterial coronaria y con el síndrome de ovario poliquístico. El síndrome de ovario poliquístico se caracteriza por un exceso de andrógenos y disfunción ovárica. Evidencia emergente sugiere que los efectos metabólicos a largo plazo y las complicaciones cardiovasculares observadas en este síndrome pueden estar relacionadas con la presencia de un estado inflamatorio crónico leve. Es poco claro si el exceso de andrógenos promueve un estado inflamatorio o, contrariamente, si las moléculas inflamatorias estimulan la producción de andrógenos. La detección temprana de los factores de riesgo ayudará en la prevención y el control de las enfermedades cardiovasculares, dado que las alteraciones metabólicas asociadas con este síndrome pueden predisponer a peores resultados de salud cardiovascular.

Sevoflurane topical analgesia for intractable pain with suicidal ideation.

Proper symptom management to improve quality of dying is mandatory in palliative care patients. Home-based control of pain caused by leg ulcers is challenging, especially when the pain is severe and refractory to conventional analgesics, the patient is intolerant to opioids and refuses invasive measures. This was the case for an 87-year-old woman under oncological palliative care who suffered from a leg ulcer causing refractory pain, which produced suicidal ideation. Leg amputation was indicated, but she had signed a living will refusing any invasive measures. After obtaining written informed consent, sevoflurane was applied topically on the ulcer, which resulted in a rapid and long-lasting reduction of pain. Daily self-administration of sevoflurane successfully controlled the wound pain and the patient abandoned her suicidal ideation, the wound healed 35 days later, and her quality of dying improved remarkably. Topical sevoflurane deserves further research on ulcers of vascular and also neoplastic aetiology.

At-home Topical Sevoflurane Added to the Conventional Analgesic Treatment for Painful leg Ulcers Greatly Improved the Analgesic Effectiveness and Reduced Opioid Consumption in a Single-Center Retrospective Comparative Study with one-Year Follow-up.

The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. This study was aimed to compare the analgesic effectiveness and safety of systemic analgesics alone or plus at-home topical sevoflurane for the management of patients with painful nonrevascularizable leg ulcers who were referred to a Pain Clinic by their attending vascular surgeons. We reviewed charts of patients treated in a single Pain Clinic with analgesic Standard of Care either alone (group SoC) or plus at-home topical sevoflurane (group SoC + Sevo), according to safety criteria. The area under the curve of pain over a year (AUC-Pain) was the primary outcome for analgesic effectiveness. Opioids were converted into Oral Morphine Milligram Equivalents. Groups SoC (n = 26) and SoC + Sevo (n = 38) were similar in baseline characteristics. Compared to SoC, median values [interquartile range] of area under the curve of pain for one-year follow-up were markedly lower for SoC + Sevo (54 [35-65] vs. 15 [11-23]; p < 0.000001, U Mann-Whitney test). Oral Morphine Milligram Equivalents were similar at baseline (SoC: 78.5 [22.5-135] vs. SoC + Sevo: 101.3 [30-160]; p = 0.753), but significantly lower for SoC + Sevo at three (120 [22.5-202.5] vs. 30 [0-80]; p = 0.005), six (120 [11.3-160] vs. 20 [0-67.5]; p = 0.004), nine (114.4 [0-154] vs. 0 [0-37]; p = 0.018), and 12 months (114.4 [0-154] vs. 0 [0-20]; p = 0.001). Multiple linear regression analysis revealed the addition of sevoflurane to be the most likely variable to explain this difference in outcome (ß:-33.408; p < 0.000001). Nine patients (24%) in SoC + Sevo had adverse effects attributed to sevoflurane, but only one patient needed to stop using sevoflurane due severe dermatitis. In conclusion, the addition of topical sevoflurane to the analgesic standard of care in patients with painful nonrevascularizable leg ulcers was a well-tolerated therapy that significantly improved pain control and allowed for a significant reduction in opioid consumption.

[Subclinical acute intermittent porphyria. An uncommon cause of chronic hepatitis]. / Porfiria aguda intermitente subclínica. Etiología inusual de hepatitis crónica.

Acute porphyria is a term that encompasses a group of hereditary disorders involving defects in heme metabolism, characterized by acute episodes of abdominal pain, acute hypertension, tachycardia and neuropsychiatric disorders, sometimes leading to convulsions, ascending paralysis and coma. Misdiagnosis or delayed diagnosis can seriously worsen prognosis. We report the case of a woman with subclinical acute intermittent porphyria and chronic hepatitis incidentally diagnosed due to transaminase elevation on laboratory analysis.

Topical sevofluran: a galenic experience.

Sevoflurane is a volatile liquid from the family of ether-derived alogenated hydrocarbons that is approved for the induction and  maintenance of inhalational general anesthesia in the hospital setting. This review describes the pioneering experience of a Spanish Pain Unit in the  home treatment of complicated painful wounds using topical sevoflurane  instillations according to a protocol approved for off-label use. Aspects of  safety and efficacy, both analgesic, antimicrobial and pro-healing are  addressed, and some future lines of research are discussed in terms of  new formulations for topical use. After more than seven years of use of the protocol, an experience of over 70,000 applications of topical sevoflurane  has been gained. In general terms, the analgesic effect appears quickly, is  highly intense and persists for several hours. As a result, patients can  reduce their consumption of systemic analgesics and benefit from an  improvement in their quality of life. In addition, there are signs that  suggest sevoflurane also possesses antimicrobial and pro-healing  properties. Regarding safety, pruritus at the level of the periulcerous skin  is the most frequently reported adverse effect, although it is usually  transient and well-tolerated, and no systemic toxicity has been reported.  Overall, the risk-benefit balance of the drug has so far been very  favorable. To avoid manipulation of this volatile liquid, we have developed  a new formulation of sevoflurane in gel form, which has made it possible  to successfully apply sevoflurane in the context of painful pathologies  where the skin remains intact. Furthermore, these types of new  formulations, including sevoflurane microspheres, which we have also  developed, could improve the efficacy and safety of topical sevoflurane  while reducing the occupational exposure of healthcare staff. This means  that the development of new formulations is a field with a very promising  future.

El sevoflurano es un líquido volátil de la familia de los hidrocarburos  alogenados derivados del éter que está aprobado para realizar la inducción y el mantenimiento de la anestesia general inhalatoria en ambiente  exclusivamente hospitalario. En esta revisión se expone la experiencia  pionera de nuestra Unidad del Dolor en el tratamiento domiciliario de  heridas dolorosas complejas mediante irrigaciones de sevoflurano tópico  según un protocolo aprobado para su uso fuera de ficha técnica. Se  abordan aspectos de seguridad y eficacia, tanto analgésica como  antimicrobiana y procicatrizante, y se comentan algunas líneas de futuro  en cuanto a nuevas formulaciones para uso tópico. Tras más de 7 años de  vigencia del referido protocolo, contamos con una experiencia acumulada  de más de 70.000 aplicaciones de sevoflurano tópico. En líneas generales,  el efecto analgésico aparece rápidamente en cuestión de minutos, es de  gran intensidad, y de duración prolongada por espacio de varias horas;  gracias a ello los pacientes pueden reducir el consumo de analgésicos sistémicos y, en general, su calidad de vida mejora. Además,  existen indicios que sugieren que también ejerce acción antimicrobiana y  procicatrizante. En cuanto a seguridad, el prurito a nivel de la piel  periulcerosa es el efecto adverso más frecuentemente comunicado,  aunque suele ser transitorio y bien tolerado, y no hay signos sugerentes  de toxicidad sistémica. Globalmente, el balance beneficio-riesgo es muy  favorable para los pacientes hasta el momento. Para evitar la manipulación de la presentación líquida y volátil hemos desarrollado una nueva  formulación de sevoflurano en tipo gel, lo cual ha permitido tratar  satisfactoriamente patologías dolorosas que cursan con piel íntegra;  además, este tipo de nuevas formulaciones, incluyendo las microesferas de sevoflurano que también desarrollamos, podrían mejorar la eficacia y la  seguridad del fármaco tópico a la vez que se reduce la exposición  ocupacional del personal sanitario, por lo que el desarrollo de nuevas  formulaciones es un campo con un futuro muy prometedor.

Review of binary, ternary and quaternary mixtures for induction and maintenance of opioid free anesthesia.

OBJECTIVE: To describe and organize the current information available on  binary, ternary and/or quaternary mixtures used in opioid-free anesthesia (OFA), as well as their physicochemical stability, in order to  facilitate its correct administration, optimize its use, and prevent potential  effectiveness and safety issues. METHOD: A systematic review of the literature on OFA was conducted in  PubMed/Medline, Trissel, Micromedex, Lexicomp,  ww.ahfsdruginformation.com, ASHP's Extended Stability for Parenteral Drugs, and www.stabilis.org. Only articles published in English or Spanish until May 2020 and with  access to full text were considered. MeSH terms used included: "drug  incompatibility" AND "opioid-free anesthesia" AND "administration, intravenous" AND "dexmedetomidine" AND "lidocaine"  AND "ketamine" AND "magnesium sulphate" OR "infusions, intravenous. A  first search was carried out in PubMed/Medline that included OFA clinical cases. The results obtained were collected in a database. A second search  was carried out on the incompatibilities of intravenous mixtures.  Information was compiled on mutually-compatible/incompatible drugs,  reference concentrations, stability time at room temperature (23 ± 2 °C)  and under refrigeration (4 ± 2 ºC), type of administration recommended,  and relevant results and conclusions. Two two-dimensional tables on the  compatibility of each drug combination were created for administration as  Y-site infusion or as a mixture in a single solution. RESULTS: Seven hundred and eighty articles were identified, with the full  text of 203 being accessed. A total of 4,762 cases treated with OFA  protocols were chronologically collected from 32 different publications. Administration of two concomitant drugs was the most usual  regimen (42.4%). The most frequently drugs were dexmedetomidine (25  studies), ketamine hydrochloride (25 studies) and lidocaine (14 studies).  Compatibility/incompatibility data was collected for 11 drugs, associated to  7 pharmacological groups; compatibility with Y-site administration was  found in 43 of 55 combinations (78.18%) and with integration into one  single solution in 13 of 55 drug combinations (23.63%). None of the  sources reviewed reported any adverse results related to potential  pharmacological incompatibilities. CONCLUSIONS: Despite the availability of multiple OFA protocols, few studies analyze the compatibility between binary drug mixtures. No  information exists as yet regarding compatibilities in the context of ternary and quaternary mixtures.  Despite the availability of multiple OFA  protocols, few studies analyze the compatibility between binary drug  mixtures. No information exists as yet regarding compatibilities in the  context of ternary and quaternary mixtures.

Objetivo: Describir y estructurar la información actual disponible sobre mezclas binarias, ternarias y/o cuaternarias empleadas en una  "anestesia libre de opiáceos", así como su estabilidad fisicoquímica, para  facilitar su correcta administración, optimizar su uso y prevenir posibles  problemas de efectividad o seguridad.Método: Revisión sistemática de la literatura sobre anestesia libre de opiáceos en PubMed/Medline, Trissel, Micromedex, Lexicomp, AHFS  Drug Information, Extended Stability for Parenteral Drugs y Stabilis Web.  Artículos publicados en inglés o español hasta mayo de 2020 y con acceso  a texto completo. Se emplearon los términos MeSH: "Drug Incompatibility" AND "Opioid Free Anesthesia" AND "Administration,  Intravenous" AND "Dexmedetomidine" AND "Lidocaine" AND "Ketamine"  AND "Sulphate Magnesium" OR "Infusions, Intravenous". Se realizó una  primera búsqueda en PubMed/Medline incluyendo casos clínicos de  anestesia general tipo anestesia libre de opiáceos. Los resultados  obtenidos se estructuraron en una base de datos. La segunda búsqueda  fue sobre incompatibilidades de las mezclas intravenosas. Se recogieron  medicamentos compatibles/ incompatibles; concentraciones de referencia; tiempo de estabilidad a temperatura ambiente (23 ± 2 °C) y en  refrigeración (4 ± 2 °C); tipo de administración recomendada y resultados  y conclusiones relevantes. Se crearon phardos tablas bidimensionales de la compatibilidad de cada combinación de fármacos para la administración en Y o en mezcla en una sola solución.Resultados: Se identificaron 780 artículos; se accedió al texto completo de 203. Se recogieron de forma cronológica los 4.762 casos  tratados en 32 diferentes publicaciones con protocolos de anestesia libre de opiáceos. El uso de dos fármacos fue la asociación más frecuente (42,4%). Los fármacos más empleados fueron dexmedetomidina (25 trabajos), clorhidrato de ketamina (25 trabajos) y lidocaína (14  trabajos). Se recopiló información de compatibilidad/incompatibilidad de  11 medicamentos, asociados a 7 grupos farmacológicos, encontrándose  compatibilidad en Y en 43 de 55 combinaciones (78,18%) y en mezcla en  una sola solución en 13 de 55 combinaciones de fármacos (23,63%). En  ningún trabajo publicado se expone algún tipo de evento adverso en  relación con una posible incompatibilidad farmacológica.Conclusiones: Existen múltiples protocolos de anestesia libre de  piáceos, pero los estudios de compatibilidad entre las diferentes mezclas  de fármacos empleadas son muy limitados cuando se trata de mezclas  binarias, y no existe información en el caso de mezclas ternarias y  cuaternarias.

Cost-effectiveness analysis of domiciliary topical sevoflurane for painful leg ulcers.

OBJECTIVES: The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We conducted a Bayesian cost-effectiveness analysis (CEA) comparing the addition of domiciliary topical sevoflurane to conventional analgesics (SEVOFLURANE, n = 38) versus conventional analgesics alone (CONVENTIONAL, n = 26) for the treatment of nonrevascularizable painful leg ulcers in an outpatient Pain Clinic of a Spanish tertiary hospital. METHODS: We used real-world data collected from charts to conduct this CEA from a public healthcare perspective and with a one-year time horizon. Costs of analgesics, visits and admissions were considered, expressed in €2016. Analgesic effectiveness was measured with SPID (Sum of Pain Intensity Difference). A Bayesian regression model was constructed, including "treatment" and baseline characteristics for patients ("arterial hypertension") and ulcers ("duration", "number", "depth", "pain") as covariates. The findings were summarized as a cost-effectiveness plane and a cost-effectiveness acceptability curve. One-way sensitivity analyses, a re-analysis excluding those patients who died or suffered from leg amputation, and an extreme scenario analysis were conducted to reduce uncertainty. RESULTS: Compared to CONVENTIONAL, SEVOFLURANE was associated with a 46% reduction in costs, and the mean incremental effectiveness (28.15±3.70 effectiveness units) was favorable to SEVOFLURANE. The estimated probability for SEVOFLURANE being dominant was 99%. The regression model showed that costs were barely influenced by any covariate, whereas effectiveness was noticeably influenced by "treatment". All sensitivity analyses showed the robustness of the model, even in the extreme scenario analysis against SEVOFLURANE. CONCLUSIONS: SEVOFLURANE was dominant over CONVENTIONAL as it was less expensive and much more effective.