Gut microbiology of UK care home residents: a cross-sectional analysis from a randomised controlled trial.

OBJECTIVE: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents. METHODS: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin. RESULTS: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home. DISCUSSION: We demonstrated that care home residents harbour significant levels of antimicrobial-resistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting.

Resultados de los pacientes operados de queratoplastia terapéutica en la provincia de Matanzas

Introducción: la queratoplastia terapéutica se define como un procedimiento cuyo propósito es contribuir a erradicar o reducir la infección cuando la terapia médica máxima no es eficaz para lograr este fin. Objetivo: evaluar la evolución y resultados de los pacientes operados de queratoplastia terapéutica. Materiales y métodos: se realizó un estudio descriptivo transversal en un universo de 15 pacientes con diagnóstico de úlcera grave corneal. Dichos pacientes fueron operados de queratoplastia terapéutica en el Servicio de Córnea del Hospital Universitario Comandante Faustino Pérez Hernández, de la provincia de Matanzas, entre abril de 2017 y febrero de 2020, y dieron su consentimiento informado para participar en la investigación. Resultados: predominó el sexo masculino, con un 53,3 % y una media de edad de 58,8 años. Como factores predisponentes, prevaleció el antecedente de trauma en el 33,3 %, seguido del uso de lentes de contacto y la diabetes mellitus como enfermedad sistémica asociada. Las úlceras de etiología micótica predominaron en el 26,6 % de los casos; la perforación corneal y el descemetocele se presentaron en el 40 % y 26,6 % de los pacientes respectivamente. Durante el primer mes, las complicaciones postoperatorias más frecuentes fueron la recidiva de la sepsis y la necrosis del injerto. Por su parte, la opacidad y vascularización corneal fueron las secuelas más frecuentes. Conclusiones: la demora en iniciar el protocolo de tratamiento adecuado provoca cuadros severos de la enfermedad, realizando queratoplastia "en caliente" en córneas perforadas o con necrosis, que devienen complicaciones postoperatorias y secuelas no alentadoras para los pacientes.

Introduction: therapeutic keratoplasty is defined as a procedure whose purpose is to help eradicate or reduce the infection when maximum medical therapy is not efficacious to achieve this end. Objective: to evaluate the evolution and results of the patients operated on therapeutic keratoplasty. Materials and methods: a cross-sectional, descriptive study was carried out in a universe of 15 patients with a diagnosis of severe corneal ulcer. The patients underwent therapeutic keratoplasty surgeries in the Cornea Service of the Clinical Surgical University Hospital Comandante Faustino Perez Hernandez, in the province of Matanzas, between April 2017 and May 2020, and gave their informed consent to participate in the research. Results: male gender predominated, with 53.3% and a mean age of 58.8 years. As predisposing factors, trauma antecedent predominated in 33.3%, followed by the use of contact lenses and diabetes mellitus as associated systemic disease. Ulcers of mycotic etiology predominated in 26.6% of the cases; corneal perforation and descemetoceles occurred in 40% and 26.6% of the cases respectively. During the first month, the most frequent postsurgery complications were recidival sepsis and graft necrosis. On the other hand, corneal opacity and vascularization were the most frequent sequels. Conclusions: the delay in initiating the adequated protocol treatment causes severe symptoms of the disease that lead to "in hot" keratoplasty in perforated or necrosed corneas, causing postsurgery complications and non-encouraging sequels for patients.

Interaction of Therapeutic d-Peptides with Aß42 Monomers, Thermodynamics, and Binding Analysis.

The aggregation of the amyloid-ß (Aß) peptide is a major hallmark of Alzheimer's disease. This peptide can aggregate into oligomers, proto-fibrils, and mature fibrils, which eventually assemble into amyloid plaques. The peptide monomers are the smallest assembly units and play an important role in most of the individual processes involved in amyloid fibril formation, such as primary and secondary nucleation and elongation. Several d-peptides have been confirmed as promising candidates to inhibit the aggregation of Aß into toxic oligomers and fibrils by specifically interacting with monomeric species. In this work, we elucidate the structural interaction and thermodynamics of binding between three d-peptides (D3, ANK6, and RD2) and Aß42 monomers by means of enhanced molecular dynamics simulations. Our study derives thermodynamic energies in good agreement with experimental values and suggests that there is an enhanced binding for D3 and ANK6, which leads to more stable complexes than for RD2. The binding of D3 to Aß42 is shown to be weakly exothermic and mainly entropically driven, whereas the complex formation between the ANK6 and RD2 with the Aß42 free monomer is weakly endothermic. In addition, the changes in the solvent-accessible surface area and the radius of gyration support that the binding between Aß42 and d-peptides is mainly driven by electrostatic and hydrophobic interactions and leads to more compact conformations.

Combination of the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis, BB-12 Has Limited Effect on Biomarkers of Immunity and Inflammation in Older People Resident in Care Homes: Results From the Probiotics to Reduce Infections iN CarE home reSidentS Randomized, Controlled Trial.

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).

Relationships Between Age, Frailty, Length of Care Home Residence and Biomarkers of Immunity and Inflammation in Older Care Home Residents in the United Kingdom.

Aging is associated with changes to the immune system, collectively termed immunosenescence and inflammageing. However, the relationships among age, frailty, and immune parameters in older people resident in care homes are not well described. We assessed immune and inflammatory parameters in 184 United Kingdom care home residents aged over 65 years and how they relate to age, frailty index, and length of care home residence. Linear regression was used to identify the independent contribution of age, frailty, and length of care home residence to the various immune parameters as dependent variables. Participants had a mean age (±SD) of 85.3 ± 7.5 years, had been residing in the care home for a mean (±SD) of 1.9 ± 2.2 years at the time of study commencement, and 40.7% were severely frail. Length of care home residence and frailty index were correlated but age and frailty index and age and length of care home residence were not significantly correlated. All components of the full blood count, apart from total lymphocytes, were within the reference range; 31% of participants had blood lymphocyte numbers below the lower value of the reference range. Among the components of the full blood count, platelet numbers were positively associated with frailty index. Amongst plasma inflammatory markers, C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1ra), soluble E-selectin and interferon gamma-induced protein 10 (IP-10) were positively associated with frailty. Plasma soluble vascular cell adhesion molecule 1 (sVCAM-1), IP-10 and tumor necrosis factor receptor II (TNFRII) were positively associated with age. Plasma monocyte chemoattractant protein 1 was positively associated with length of care home residence. Frailty was an independent predictor of platelet numbers, plasma CRP, IL-1ra, IP-10, and sE-selectin. Age was an independent predictor of activated monocytes and plasma IP-10, TNFRII and sVCAM-1. Length of care home residence was an independent predictor of plasma MCP-1. This study concludes that there are independent links between increased frailty and inflammation and between increased age and inflammation amongst older people resident in care homes in the United Kingdom. Since, inflammation is known to contribute to morbidity and mortality in older people, the causes and consequences of inflammation in this population should be further explored.

Characterization of insufficient responders to anti-tumor necrosis factor therapies in patients with moderate to severe psoriasis: real-world data from the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have dramatically changed the management of moderate to severe psoriasis; however, few US real-world studies characterize the unmet needs of patients who do not respond to biologic therapies. This study examined the characteristics at enrollment of patients with moderate to severe psoriasis who had insufficient responses to anti-tumor necrosis factor therapies (anti-TNFs). METHODS: Patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated an anti-TNF at enrollment were stratified on the basis of body surface area (BSA) improvement to <3% or a 75% improvement from enrollment to the 6-month follow-up visit (response versus insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for those who received anti-TNFs. RESULTS: Of 180 anti-TNF initiators who had ≥1 follow-up visit, 50.6% were classified as responders. Logistic regression modeling showed that female sex was significantly associated with a decreased likelihood of achieving a response (OR = 0.534, 95% CI = 0.289-0.988, p = .046). CONCLUSION: Despite the small sample size and short follow-up period, these findings may help dermatologists to identify patients with moderate to severe psoriasis who have unmet treatment needs.

Characterization of insufficient responders to ustekinumab in patients with moderate-to-severe psoriasis in the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have revolutionized the management of moderate-to-severe psoriasis; however, there are a limited number of US real-world studies characterizing patients based on response to these treatments. This study examined characteristics at enrollment and change in outcomes of US patients with moderate-to-severe psoriasis who achieved insufficient responses with ustekinumab. METHODS: This study included patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated ustekinumab at enrollment and who were stratified based on achievement of psoriasis body surface area improving to <3% or by 75% from enrollment to the 6-month follow-up visit (response vs insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for ustekinumab responders and insufficient responders. RESULTS: Of the 178 patients who initiated ustekinumab in the Corrona Psoriasis Registry and had ≥1 follow-up visit, 99 (55.6%) were classified as responders at the 6-month follow-up visit. Logistic regression modeling showed that increasing age was significantly associated with a decreased likelihood of achieving a response (OR, 0.981 [95%CI, 0.962-0.999]; p = .049). CONCLUSIONS: These findings may help dermatologists characterize patients with moderate-to-severe psoriasis who have inadequate responses to biologic treatments.

Falta de evidencia de transmisión vertical y hallazgos histopatológicos en restos placentarios de pacientes con diagnóstico de Síndrome Respiratorio Agudo Severo por Coronavirus 2 (SARS-CoV-2) en Guatemala / Lack of evidence of vertical transmission and histopathological findings in placental remains of patients diagnosed with Severe Acute Respiratory Syndrome of Coronavirus 2 (SARS-CoV-2) in Guatemala

El primer caso de infección por el virus SARS-CoV-2, fue reportado en la ciudad de Wuhan, China en diciem-bre de 2019. Desde entonces la enfermedad se ha dispersado a más de 188 países, confirmándose más de 53 millones de casos a nivel mundial. El 13 de marzo de 2020 se reportó el primer caso de COVID-19 en Guatemala y, a mediados del mes de noviembre, se han reportado más de 116,000 casos, 4,000 fallecidos y 106,000 recu-perados; con una tasa de mortalidad de 23 por cada 100,000 habitantes y una letalidad del 3.4%. Hasta ahora, la literatura científica disponible abarca ciertos aspectos de salud reproductiva, mientras se continúa recopilando más información que permita conocer más de su impacto real durante el proceso infeccioso y las secuelas derivadas de éste. La presente es una revisión histopatológica de restos placentarios de tres mujeres con resultado positivo para SARS-CoV-2, ingresadas en un hospital privado de la Ciudad de Guatemala. El examen histopatológico del tejido placentario aporta información importante sobre la salud de la madre y del feto. Todos los casos revelaron signos macroscópicos y microscópicos de disfunción placentaria por mala perfusión vascular materna, con for-mación de infartos hemorrágicos y daño placentario asociado con efectos adversos en el embarazo. Agregando a esto, dos neonatos presentaron un resultado negativo para SARS-CoV-2 y uno falleció. Es de suma importancia el estudio de la placenta de madres positivas a SARS-CoV-2 para conocer el rol de esta durante el embarazo y también, indagar en la posibilidad de transmisión vertical.

The first infection caused by the SARS-CoV-2 virus, was reported in the city of Wuhan, China in December 2019. Since then, the disease has spread to more than 188 countries and territories, confirming more than 53 million cases worldwide. On March 13th 2020, the first case of COVID-19 was reported in Guatemala and by the middle of November, more than 116,000 cases have been reported, 4,000 deaths and 106,000 recovered; with a mortality rate of 23 per 100,000 inhabitants and a fatality of 3.4%. Until now, the available scientific literature covers certain aspects of reproductive health, whilst more information continues to be collected that allows us to know more about its real impact on the human body during the infectious process and the consequences derived from it. This is a histopathological report of placental tissue obtained from three women with a positive result for SARS-CoV-2, admitted to a private hospital in Guatemala City. Added to this, the histopathological examination of placental tissue obtained, provides important information about the health of the mother and fetus. All cases revealed macroscopic and microscopic signs of placental dysfunction due to poor maternal vascular perfusion, with evidence of hemorrhagic infarcts and placental damage that is associated with adverse effects in pregnancy. In addition, two newborns had a negative result for SARS-CoV-2 and one newborn died. The study of the placenta of newborns of SARS-CoV-2 positive mothers is of utmost importance to understand its role during pregnancy and also, investigate the possibility of vertical transmission..

In Vitro Effects of Live and Heat-Inactivated Bifidobacterium animalis Subsp. Lactis, BB-12 and Lactobacillus rhamnosus GG on Caco-2 Cells.

Probiotic-host interaction can be cell-to-cell or through metabolite production. Dead (inactive) organisms could interact with the host, leading to local effects and possible health benefits. This research examined the effects of live and heat-inactivated Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) and Lactobacillus rhamnosus GG (LGG) on cultured Caco-2 cells focusing on epithelial integrity and production of inflammatory mediators. Live organisms increased transepithelial electrical resistance (TEER), a barrier-integrity marker, with LGG having a greater effect than BB-12. When mildly heat-treated, both organisms had a more modest effect on TEER than when alive. When they were heat-inactivated, both organisms had only a limited effect on TEER. Neither live nor heat-inactivated organisms affected production of six inflammatory mediators produced by Caco-2 cells compared to control conditions. Pre-treatment with heat-inactivated LGG or BB-12 did not alter the decline in TEER caused by exposure to an inflammatory cocktail of cytokines. However, pre-treatment of Caco-2 cells with heat-inactivated organisms alone or their combination decreased the production of interleukin (IL)-6, IL-18, and vascular endothelial growth factor. To conclude, while the live organisms improve the epithelial barrier using this model, neither live nor heat-inactivated organisms directly elicit an inflammatory response by the epithelium. Pre-treatment with heat-inactivated BB-12 or LGG can reduce some components of the response induced by an inflammatory stimulus.

Time to treatment failure following initiation of fingolimod versus teriflunomide for multiple sclerosis: a retrospective US claims study.

Objective: Disease modifying therapies (DMTs) for multiple sclerosis (MS) aim to delay progression and reduce relapses. Evidence is limited on the comparative effectiveness of the oral DMTs fingolimod and teriflunomide. This study evaluated time to treatment failure among patients with MS who initiated fingolimod versus teriflunomide in real-world settings.Methods: The retrospective cohort included 18-64 year old patients diagnosed with MS who initiated fingolimod or teriflunomide during 12 September 2012 to 30 September 2015 within MarketScan Commercial and Medicare Claims. Patients were followed from treatment initiation (index date) until first treatment failure or censoring. Treatment failure was defined as the first occurrence of MS relapse (identified using a validated algorithm) or treatment discontinuation (≥60 day supply gap). Treatment failure was examined through Kaplan-Meier analysis and multivariable Cox regression adjusting for 1 year baseline factors (age, gender, plan type, region, index year, prior DMT use, baseline relapses, Charlson Comorbidity Index [CCI] and MS symptoms).Results: On average, patients treated with fingolimod (n = 2704) were younger (43.6 versus 49.8 years) with lower CCI (0.4 versus 0.7) and more relapses at baseline (0.46 versus 0.42) than those treated with teriflunomide (n = 1859). Median time to treatment failure was 19.5 months with fingolimod versus 9.6 months with teriflunomide (p < .001). After controlling key demographic and clinical characteristics through multivariable regression, fingolimod was associated with 38.9% lower hazards of treatment failure versus teriflunomide (adjusted hazard ratio = 0.611; 95% CI: 0.559-0.669; p < .001).Conclusions: In a large cohort of US adults with MS, controlling for key baseline characteristics, fingolimod was associated with significantly longer time to treatment failure and lower risk of treatment failure compared with teriflunomide.

Exploration of the Product of the 5-Point Investigator's Global Assessment and Body Surface Area (IGA × BSA) as a Practical Minimal Disease Activity Goal in Patients with Moderate-to-Severe Psoriasis.

BACKGROUND/AIMS: In the treat-to-target era, psoriasis disease activity measures that can be easily performed in routine clinical practice are needed. This retrospective pooled analysis explored cutoff values of the product of the 5-point Investigator's Global Assessment and percentage of affected body surface area (IGA × BSA) correlating with achievement of minimal disease activity (MDA). METHODS: Post hoc analysis of the phase 3 clinical trials ERASURE, FIXTURE, FEATURE, and JUNCTURE was conducted to determine associations between IGA × BSA and 2 MDA definitions (Psoriasis Area and Severity Index [PASI] 90 and Dermatology Life Quality Index [DLQI] 0/1, or PASI score ≤1 or BSA <3%) in patients with moderate-to-severe psoriasis receiving secukinumab 300 mg. For each definition of MDA, a range of possible cutoff values of IGA × BSA was examined at each time point. The optimal cutoff value was determined using Youden index (YI), calculated as (sensitivity + specificity - 1). RESULTS: For MDA defined as PASI 90 and DLQI 0/1, optimal IGA × BSA cutoffs were 2.10 at week 12 (YI, 0.60; sensitivity, 0.78; specificity, 0.82), 1.02 at week 24 (YI, 0.55; sensitivity, 0.73; specificity, 0.82), and 1.00 at week 52 (YI, 0.65; sensitivity, 0.79; specificity, 0.86). For MDA defined as PASI score ≤1 or BSA <3%, optimal IGA × BSA cutoffs were 2.98 at week 12 (YI, 0.91; sensitivity, 0.99; specificity, 0.92), 2.80 at week 24 (YI, 0.94; sensitivity, 0.99; specificity, 0.95), and 3.00 at week 52 (YI, 0.96; sensitivity, 1.00; specificity, 0.96). CONCLUSION: IGA × BSA could be a valid measure highly associated with achievement of MDA.

Impact of psoriasis severity on patient-reported clinical symptoms, health-related quality of life and work productivity among US patients: real-world data from the Corrona Psoriasis Registry.

OBJECTIVES: This analysis examined the association between psoriasis severity, assessed by body surface area (BSA) and the Investigator's Global Assessment (IGA; previously used only in clinical trials), and patient-reported outcomes (PROs) in a real-world setting. DESIGN: Cross-sectional analysis within the Corrona Psoriasis Registry, an independent, prospective registry. SETTING: 70 dermatology practices in the USA. PARTICIPANTS: 1529 adult patients with psoriasis being treated with biological or non-biological systemic psoriasis treatment by 31 May 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Psoriasis severity was assessed by percentage of affected BSA (mild (0%-5%), moderate (>5%-10%), severe (>10%-15%), very severe (>15%)) and IGA scores (clear/almost clear (0-1), mild (2), moderate (3), severe (4)). PROs (pain, itch, fatigue; Dermatology Life Quality Index [DLQI]; EuroQoL Visual Analogue Scale [EQ-VAS]; Work Productivity and Activity Impairment [WPAI]) were compared across BSA and IGA levels using analysis of variance and X2 tests. The association between psoriasis severity and PROs was examined using multivariable regression models. RESULTS: The mean age was 50.6 years and 47% of patients were female. Consistently with more severe psoriasis, symptoms worsened, DLQI scores increased (p<0.05 for each level of BSA and IGA), EQ-VAS decreased (p<0.05 for each level of BSA and IGA) and WPAI scores increased. By BSA score, moderate to very severe psoriasis was associated with poorer outcomes for the 'impairment while working' and 'daily activities impaired' WPAI domains (all p<0.05 vs mild psoriasis). Very severe psoriasis was associated with increased 'work hours missed' and 'work hours affected' (both p<0.05 vs mild psoriasis) Findings were similar by IGA. Results were confirmed by multivariable regression analyses. CONCLUSIONS: In a real-world setting, more severe psoriasis, assessed by BSA and IGA, was consistently associated with worse PROs.

Degeneración esferoidea. Reporte de caso / Spheroidal degeneration. Case report

RESUMEN Se reportó el caso clínico de una fémina de 50 años de edad. Acudió a los Servicios de Oftalmología, del Hospital Provincial Comandante Faustino Pérez Hernández, de Matanzas. Refirió síntomas irritativos y disminución visual por el ojo izquierdo. El examen oftalmológico mostró en dicho ojo la presencia de lesiones esferoideas de color ámbar, conjuntivo corneales en periferia (horas 3-4 y 9). Se extendían en banda a la córnea central, algunas con aspecto nodular. En el ojo derecho presentaba lesiones similares pero localizadas mayoritariamente en la periferia corneal y conjuntiva horas 3 y 9. Con estos elementos se estableció diagnóstico clínico de degeneración esferoidea, enfermedad degenerativa corneal poco frecuente y generalmente asintomática siempre que no progrese y afecte la visión. Se aplicó como tratamiento una queratectomia superficial, manual, con colocación de una lente de contacto terapéutica en el ojo izquierdo, sin complicaciones. Hubo regresión de los síntomas irritativos y mejoría de la agudeza visual constatada en las consultas de seguimiento. Se recomendó la necesidad de protección solar al constituir las radiaciones ultravioletas un factor de riesgo de importancia en el desarrollo de esta enfermedad.

ABSTRACT The authors reported the case of a woman, aged 50 years, who assisted the Ophthalmology service of the Provincial Hospital "Comandante Faustino Pérez Hernández", of Matanzas. She referred irritant symptoms and left eye visual decrease. The ophthalmologic examination showed the presence of amber-color spheroidal lesions, corneal conjunctives in periphery (3-4 and 9 hours) in that eye. They extended in bands to the central cornea, some of them with nodular aspect. There were similar lesions in the right eye, but they were located mainly corneal and peripheral conjunctive hours 3 and 9. With these elements it was established the clinical diagnosis of spheroidal degeneration, a few frequent corneal degenerative disease that is almost always asymptomatic if it does not progress and affects sight. As a treatment the patient underwent a manual, superficial keratectomy with location of therapeutic contact lens without complications. There it was a regression of the irritant symptoms and an improvement of the visual acuity stated in the follow-up consultations. The patients was recommended sun protection because ultraviolet rays are important risk factors in the development of this disease.

Degeneración esferoidea. Reporte de caso / Spheroidal degeneration. Case report

RESUMEN Se reportó el caso clínico de una fémina de 50 años de edad. Acudió a los Servicios de Oftalmología, del Hospital Provincial Comandante Faustino Pérez Hernández, de Matanzas. Refirió síntomas irritativos y disminución visual por el ojo izquierdo. El examen oftalmológico mostró en dicho ojo la presencia de lesiones esferoideas de color ámbar, conjuntivo corneales en periferia (horas 3-4 y 9). Se extendían en banda a la córnea central, algunas con aspecto nodular. En el ojo derecho presentaba lesiones similares pero localizadas mayoritariamente en la periferia corneal y conjuntiva horas 3 y 9. Con estos elementos se estableció diagnóstico clínico de degeneración esferoidea, enfermedad degenerativa corneal poco frecuente y generalmente asintomática siempre que no progrese y afecte la visión. Se aplicó como tratamiento una queratectomia superficial, manual, con colocación de una lente de contacto terapéutica en el ojo izquierdo, sin complicaciones. Hubo regresión de los síntomas irritativos y mejoría de la agudeza visual constatada en las consultas de seguimiento. Se recomendó la necesidad de protección solar al constituir las radiaciones ultravioletas un factor de riesgo de importancia en el desarrollo de esta enfermedad (AU).

ABSTRACT The authors reported the case of a woman, aged 50 years, who assisted the Ophthalmology service of the Provincial Hospital "Comandante Faustino Pérez Hernández", of Matanzas. She referred irritant symptoms and left eye visual decrease. The ophthalmologic examination showed the presence of amber-color spheroidal lesions, corneal conjunctives in periphery (3-4 and 9 hours) in that eye. They extended in bands to the central cornea, some of them with nodular aspect. There were similar lesions in the right eye, but they were located mainly corneal and peripheral conjunctive hours 3 and 9. With these elements it was established the clinical diagnosis of spheroidal degeneration, a few frequent corneal degenerative disease that is almost always asymptomatic if it does not progress and affects sight. As a treatment the patient underwent a manual, superficial keratectomy with location of therapeutic contact lens without complications. There it was a regression of the irritant symptoms and an improvement of the visual acuity stated in the follow-up consultations. The patients was recommended sun protection because ultraviolet rays are important risk factors in the development of this disease (AU).

The Impact of Price Reductions After Loss of Exclusivity in a Cost-Effectiveness Analysis: Fingolimod Versus Interferon Beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Cost-effectiveness analyses tend not to take into account the availability of lower-priced generics following loss of exclusivity (LOE) of branded products. By not considering these generics, which are typically adopted quickly, total costs are likely to be overestimated and may be unreflective of real-world payer conditions in the United States. OBJECTIVE: To assess the impact of including future price reductions following LOE on the cost-effectiveness of fingolimod versus intramuscularly administered interferon beta-1a (IM IFNß-1a) as treatments for multiple sclerosis. METHODS: This model was adopted from a previously published Markov model and was conducted from a U.S. payer perspective over a 10-year time horizon. Patients with relapsing-remitting multiple sclerosis entered the model and received either fingolimod (an oral therapy) or IM IFNß-1a (an injectable). These treatments reflect the interventions studied in the TRANSFORMS randomized clinical trial. Clinical, cost, and utility inputs were based on a recent cost-effectiveness review of therapies for multiple sclerosis. To model LOE, price reductions and the proportion of patients switching to generic versions following LOE were based on published estimates. Price reductions varied to reflect the difference in product types (oral vs. large molecule injectable). Assumptions were also made around the proportion of patients switching to generic versions over time following LOE and the projected date of LOE. Outcomes included per-patient total direct costs (medication, administration and monitoring, and disease-related costs including relapses), quality-adjusted life-years, and the incremental cost per quality-adjusted life-year. RESULTS: Assuming no price reductions following LOE, fingolimod was considered cost-effective versus IM IFNß-1a ($118,434 per quality-adjusted life-year), despite having higher total direct costs over 10 years ($475,740 vs. $446,792). When including future price reductions following LOE, total direct costs were reduced with fingolimod and were lower than those accrued with IM IFNß-1a over the model time horizon ($308,570 vs. $442,653). Cost-effectiveness results were sensitive to changes in both clinical parameters and medication costs. Scenario analyses demonstrated that an earlier date of LOE was associated with lower total costs. CONCLUSIONS: Health economic models may predict higher total costs when the price reductions following LOE are not considered. Here, oral fingolimod was seen to be cost-saving versus IM IFNß-1a over the model time horizon when such price reductions were included. The cost implications of not accounting for future price changes may determine whether an intervention is considered cost-effective and as such may influence reimbursement decisions based on cost-effectiveness thresholds. Multiple product types (e.g., oral, injectable, and infused agents) have been approved for use as treatments for multiple sclerosis in the United States, and LOE is likely to have a different effect on each of these therapies. DISCLOSURES: This study was funded by Novartis Pharmaceuticals Corporation. Hua and Hersh report consulting fees from Novartis for work on this study. Hua also reports speaking, advisory board, and consulting fees from Biogen, Genzyme, Teva, EMD Serono, Genentech, TG Therapeutics, and Novartis for activities outside of this study. Hersh also reports speaking and consulting fees from Novartis, Biogen, Genzyme, Genentech, and EMD Serono for activities outside of this study, and research grants from PCORI and Biogen. At the time of this research, Morten and Kusel were paid employees of Costello Medical, which was contracted by Novartis to undertake some of this study's work. Lin, Cave, Herrera, and Ko were paid employees of Novartis at the time of this research. Cave, Herrera, and Ko also report owning stock in Novartis Pharmaceuticals. Varga provided services to Novartis at the time of this research and has nothing further to disclose. This research was presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2017; March 27-30, 2017; Denver, CO.

Miositis orbitaria en adolescente / Adolescents´ orbital myositis

Introducción: La miositis orbitaria aguda es una afección inflamatoria de la musculatura extrínseca ocular muchas veces de causa desconocida. Forma parte de un grupo de afecciones inflamatorias orbitarias inespecíficas englobadas bajo el término de pseudo tumor orbitario. Afecta principalmente a las mujeres jóvenes. Objetivo: Describir el caso de una adolescente con miositis orbitaria aguda, afección inflamatoria poco frecuente en la edad pediátrica. Presentación del caso: Se trata de una adolescente de 14 años, mestiza, femenina, quien sufrió dengue por tres ocasiones poco tiempo antes de presentarse con dolor ocular del ojo izquierdo, fiebre elevada intermitente, protrusión ocular intermitente, vómitos, cefalea, decaimiento, pérdida de peso y de apetito. El ojo izquierdo presentaba edema del parpado superior y limitación a la abducción, musculatura ocular extrínseca: diplopía horizontal a mirada derecha a izquierda. El ultrasonido ocular informa presencia de imagen quística que no impresiona ser de contenido hemático. El resultado de la tomografía axial computarizada de órbita y cráneo simple fue compatible con diagnóstico de miositis orbitaria. Se indicó tratamiento inmediato con esteroides orales y se remitió al Instituto de Oftalmología Ramon Pando Ferrer para seguimiento. Conclusiones: La miositis orbitaria exige un alto índice de sospecha para un diagnóstico y tratamiento correcto. El dengue pudiera estar implicado en la etiología de la enfermedad(AU)

Introduction: Acute orbitary myositis is an inflammatory condition of the extrinsic ocular musculature, often of unknown cause. It is part of a group of non-specific orbital inflammatory conditions encompassed by the term of orbital pseudotumors. It mainly affects young women. Objective: To describe the case of a teenager with acute orbital myositis which an inflammatory condition not frequent in the pediatric ages. Case presentation: This is a 14-year-old, mixed-race, female patient, who suffered dengue three times before presenting ocular pain in the left eye, intermittent high fever, intermittent ocular protrusion, vomiting, headache, weakness, loss of weight and appetite. The left eye presents edema of the upper eyelid and limitation in abduction. The extrinsic ocular musculature presented: horizontal diplopia in right to left gaze. The ocular ultrasound informs: cystic image that does not impress to be of hematic content. A computerized axial tomography of the orbit and simple skull was performed, and the result was compatible with the diagnosis of orbital myositis. Immediate treatment with oral steroids was indicated and the patient was sent to the Ramon Pando Ferrer Ophthalmology Institute for follow-up. Conclusion: Orbital myositis requires a high index of suspicion for a correct diagnosis and treatment. Dengue seems to be involved in the etiology of the disease(AU)

Miositis orbitaria en adolescente / Adolescents´ orbital myositis

Introducción: La miositis orbitaria aguda es una afección inflamatoria de la musculatura extrínseca ocular muchas veces de causa desconocida. Forma parte de un grupo de afecciones inflamatorias orbitarias inespecíficas englobadas bajo el término de pseudo tumor orbitario. Afecta principalmente a las mujeres jóvenes. Objetivo: Describir el caso de una adolescente con miositis orbitaria aguda, afección inflamatoria poco frecuente en la edad pediátrica. Presentación del caso: Se trata de una adolescente de 14 años, mestiza, femenina, quien sufrió dengue por tres ocasiones poco tiempo antes de presentarse con dolor ocular del ojo izquierdo, fiebre elevada intermitente, protrusión ocular intermitente, vómitos, cefalea, decaimiento, pérdida de peso y de apetito. El ojo izquierdo presentaba edema del parpado superior y limitación a la abducción, musculatura ocular extrínseca: diplopía horizontal a mirada derecha a izquierda. El ultrasonido ocular informa presencia de imagen quística que no impresiona ser de contenido hemático. El resultado de la tomografía axial computarizada de órbita y cráneo simple fue compatible con diagnóstico de miositis orbitaria. Se indicó tratamiento inmediato con esteroides orales y se remitió al Instituto de Oftalmología Ramon Pando Ferrer para seguimiento. Conclusiones: La miositis orbitaria exige un alto índice de sospecha para un diagnóstico y tratamiento correcto. El dengue pudiera estar implicado en la etiología de la enfermedad(AU)

Introduction: Acute orbitary myositis is an inflammatory condition of the extrinsic ocular musculature, often of unknown cause. It is part of a group of non-specific orbital inflammatory conditions encompassed by the term of orbital pseudotumors. It mainly affects young women. Objective: To describe the case of a teenager with acute orbital myositis which an inflammatory condition not frequent in the pediatric ages. Case presentation: This is a 14-year-old, mixed-race, female patient, who suffered dengue three times before presenting ocular pain in the left eye, intermittent high fever, intermittent ocular protrusion, vomiting, headache, weakness, loss of weight and appetite. The left eye presents edema of the upper eyelid and limitation in abduction. The extrinsic ocular musculature presented: horizontal diplopia in right to left gaze. The ocular ultrasound informs: cystic image that does not impress to be of hematic content. A computerized axial tomography of the orbit and simple skull was performed, and the result was compatible with the diagnosis of orbital myositis. Immediate treatment with oral steroids was indicated and the patient was sent to the Ramon Pando Ferrer Ophthalmology Institute for follow-up. Conclusion: Orbital myositis requires a high index of suspicion for a correct diagnosis and treatment. Dengue seems to be involved in the etiology of the disease(AU)

Real-world durability of relapse rate reduction in patients with multiple sclerosis receiving fingolimod for up to 3 years: a retrospective US claims database analysis.

OBJECTIVE: To assess real-world durability of reduction in relapse rates among patients with multiple sclerosis (MS) receiving fingolimod therapy over a longer-term period of follow-up. METHODS: Patients with MS who initiated fingolimod were identified from a US claims database (January 1, 2009 to September 30, 2016) and followed for 3 years post-initiation. Annualized relapse rates (ARRs) were calculated during the 1-year pre-initiation period, and during each year over the 3-year follow-up period. Time from fingolimod initiation to discontinuation (≥60-day treatment gap) was also summarized. RESULTS: Among 1599 fingolimod initiators, 1158 (72%) had continuous fingolimod use up to the start of year 2 and 937 (59%) had continuous fingolimod use up to the start of year 3. The mean baseline ARR during the 1-year pre-initiation period for all initiators was 0.51. After fingolimod initiation, mean ARRs were consistently lower in each year of follow-up: 0.25 (95% CI: 0.22, 0.28) in year 1 for all fingolimod initiators, 0.22 (0.18, 0.25) in year 2 for patients with continuous fingolimod use up to the start of year 2, and 0.23 (0.19, 0.27) in year 3 for patients with continuous fingolimod use up to the start of year 3. Median time on treatment was 33 months for all patients initiating fingolimod. CONCLUSIONS: Patients with MS who received continuous fingolimod therapy experienced a sustained reduction in relapse rates (>50% vs. baseline) during each year of a 3-year follow-up period.

Associations Between Treatment Satisfaction, Medication Beliefs, and Adherence to Disease-Modifying Therapies in Patients with Multiple Sclerosis.

BACKGROUND: Adherence to disease-modifying therapy (DMT) remains problematic for many patients with multiple sclerosis (MS). An improved understanding of factors affecting DMT adherence may inform effective interventions. This study examined associations between treatment satisfaction, medication beliefs, and DMT adherence. METHODS: A survey was mailed in 2016 to 600 adult patients with relapsing-remitting MS taking an injectable or oral DMT. Patients were sampled from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. The survey measured self-reported DMT adherence (doses taken divided by doses prescribed during previous 2-week period-adherence ≥0.80), DMT satisfaction using the Treatment Satisfaction Questionnaire for Medication version II, medication beliefs using the Beliefs About Medicines Questionnaire, and demographic and clinical covariates. Relationships between variables were examined using multivariate logistic regression. RESULTS: Final analyses included 489 usable surveys. Mean ± SD participant age was 60.5 ± 8.3 years. Most respondents were white (93.8%), female (86.6%), taking an injectable DMT (66.9%), and adherent to DMT (92.8%). Significant predictors of DMT adherence were age (odds ratio [OR], 1.086; 95% CI, 1.020-1.158; P = .011), type of DMT (oral vs. injectable; OR, 23.350; 95% CI, 2.254-241.892; P = .008), and DMT experience (naive vs. experienced; OR, 2.831; 95% CI, 1.018-7.878; P = .046). CONCLUSIONS: In patients with MS sampled from a patient registry, treatment satisfaction and medication beliefs were not significantly associated with DMT adherence. Based on significant predictors, younger patients, patients taking injectable DMTs, and patients with previous experience with another DMT(s) are at higher risk for nonadherence. Future research is warranted to assess relationships between variables in more diverse MS populations.

Direct healthcare costs and comorbidity burden among patients with psoriatic arthritis in the USA.

This study assessed the comorbidity burden and direct healthcare costs associated with psoriatic arthritis (PsA). Adults (18-64 years) with ≥ 2 claims for a PsA diagnosis ≥ 30 days apart in the Truven Health MarketScan database (July 2009-June 2014) were selected as the case group. The index date was randomly selected after the first claim for PsA. Controls free of PsA and psoriasis (PsO) in their entire claims history were assigned the same index date and were matched with the cases on age, gender, and geographic region. All patients had ≥ 12 months of continuous eligibility before and after (study period) the index date. PsA-associated comorbidities, medication use, and medical service utilization were compared between matched groups using Wilcoxon signed rank and McNemar's tests. Costs were compared using multivariable generalized linear models. The 35,061 matched pairs had a mean age of 49.11 ± 10.20 years and 52.73% were female. During the study period, PsA patients had more PsA-associated comorbidities and significantly higher medication use than controls (all-cause medications 96.64 vs. 78.95%, p < 0.0001). PsA patients had significantly greater medical service use (inpatient admissions, hospitalization days, emergency room visits, outpatient services; all p < 0.0001) and higher annual direct healthcare costs per patient than controls (adjusted cost difference [ACD] = $18,482, including higher medical costs [ACD = $6440] and all-cause pharmacy costs [ACD = $11,737]; all p < 0.0001). Overall, PsA patients had a significantly higher PsA-related comorbidity burden, healthcare utilization, and direct healthcare costs than people free of PsA and PsO, underscoring the need for more effective treatments and improved care delivery systems.