Development and evaluation of the in vitro schistosomicidal activity of solid dispersions based on 2-(-5-bromo-1-H-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide.

Among all the neglected diseases, schistosomiasis is considered the second most important parasitic infection after malaria. Praziquantel is the most widely used drug for this disease, but its exclusive use may result in the development of drug-resistant schistosomiasis. To increase the control of the disease, new drugs have been developed as alternative treatments, among them 2-(-5-bromo-1-h-indole-3-yl-methylene)-N-(naphthalene-1-ylhydrazine-carbothiamide (LQIT/LT-50), which showed promising schistosomicidal activity in nonclinical studies. However, LQIT/LT-50 presents low solubility in water, resulting in reduced bioavailability. To overcome this solubility problem, the present study aimed to develop LQIT/LT-50 solid dispersions for the treatment of schistosomiasis. Solid dispersions were prepared through the solvent method using Soluplus©, polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP K-30) as hydrophilic carriers. The formulations with the best results in the compatibility tests, aqueous solubility and preliminary stability studies have undergone solubility tests and physicochemical characterizations by Fourier-transform infrared spectroscopy (FTIR), x-ray diffractometry (XRD), exploratory differential calorimetry (DSC), thermogravimetry (TG) and Raman spectroscopy. Finally, the schistosomicidal activity was evaluated in vitro. The phycochemical analyzes showed that when using PVP K-30, there was an interaction between the PVP K-30 and LQIT/LT-50, proving the successful development of the solid dispersion. Furthermore, an increase in the solubility of the new system was observed (LQIT/LT-50:PVP K-30) in addition to the improvement in the in vitro shistosomidal activity at 1:4 (w/w) molar ratio (i.e., 20% drug loading) when compared to LQIT/LT-50 alone. The development of the LQIT/LT-50:PVP K-30 1:4 solid dispersion is encouraging for the future development of new pharmaceutical solid formulations, aiming the schistosomicidal treatment.

Proposta de protocolo clínico para tratamento conservador da incontinência urinária de urgência / Proposal for a clinical protocol for the conservative treatment of urge urinary incontinence / Propuesta de protocolo clínico para el tratamiento conservador de la incontinencia urinaria de urgencia

Objetivo:Apresentar proposta de protocolo clínico para tratamento conservador da incontinência urinária de urgência (IUU). Método: Relato de experiência fundamentado nas evidências científicas existentes e na experiência clínica dos autores que realizam consultas de enfermagem a pessoas com IUU, delineada conforme proposição do Ministério da Saúde para elaboração de protocolos clínicos. Resultados: Foi proposto um protocolo clínico com diagnóstico e intervenções de enfermagem baseados na North American Nursing Diagnosis Association (NANDA) e na Nursing Interventions Classifications, com etapas sistematizadas em verificar presença de fatores relacionados ou condições associadas ao diagnóstico, sendo eles: assoalho pélvico hiperativo, ansiedade, constipação, infecção urinária, baixa ingestão hídrica, comportamento sanitário inadequado, diabetes mellitus, prolapso de órgão pélvico, alto consumo de potenciais irritantes vesicais e persistência de sintomas. Logo após, as ações que devem ser implementadas pelo enfermeiro são descritas de forma detalhada. Conclusão: Considera-se que o fluxo e o detalhamento das ações apresentadas possam ser adotados pelos enfermeiros de forma a identificarem e tratarem pessoas com IUU, minimizando assim a prevalência do problema e fomentando a qualidade de vida dessas pessoas.

Objective: To present a proposal for a clinical protocol for the conservative treatment of urge urinary incontinence. Method: Experience report based on existing scientific evidence and clinical experience of authors who perform nursing consultations for people with urge urinary incontinence, outlined in accordance with the Brazilian Ministry of Health's proposal for the elaboration of clinical protocols. Results: A clinical protocol was proposed with nursing diagnosis and interventions based on the North American Nursing Diagnosis Association (NANDA) and Nursing Interventions Classifications (NIC), with systematized steps to verify the presence of related factors or conditions associated with the diagnosis, namely: hyperactive pelvic floor, anxiety, constipation, urinary tract infection, low fluid intake, inadequate sanitary behavior, diabetes mellitus, pelvic organ prolapse, high consumption of potential bladder irritants and persistence of symptoms. Soon after, the actions that should be implemented by the nurse were described in detail. Conclusion: It is considered that the flow and detailing of the actions presented can be adopted by nurses in order to identify and treat people with urge urinary incontinence, thus minimizing the prevalence of the problem and promoting the quality of life of these people.

Objetivo:Presentar una propuesta de protocolo clínico para el tratamiento conservador de la incontinencia urinaria de urgencia. Método: Relato de experiencia basado en evidencia científica existente y experiencia clínica de autores que realizan consultas de enfermería a personas con incontinencia urinaria de urgencia, perfilado de acuerdo con la propuesta del Ministerio de Salud para la elaboración de protocolos clínicos. Resultados: Se propuso un protocolo clínico con Diagnósticos e Intervenciones de Enfermería basado en las Clasificaciones de Intervenciones de Enfermería y Diagnósticos de Enfermería de América del Norte, con pasos sistematizados para verificar la presencia de factores relacionados o condiciones asociadas al diagnóstico, a saber: piso pélvico hiperactivo , ansiedad, estreñimiento, infección del tracto urinario, baja ingesta de líquidos, conducta sanitaria inadecuada, diabetes mellitus, prolapso de órganos pélvicos, alto consumo de potenciales irritantes vesicales y persistencia de los síntomas. Posteriormente, se describieron en detalle las acciones que debe implementar la enfermera. Conclusión: Se considera que la fluidez y el detalle de las acciones presentadas pueden ser adoptadas por los enfermeros para identificar y tratar a las personas con incontinencia urinaria de urgencia, minimizando así la prevalencia del problema y promoviendo la calidad de vida de esas personas.DESCRIPTORES:Estomaterapia. Incontinencia urinaria. Enfermería.

Progressive Multifocal Encephalopathy Holmes Tremor Successfully Treated with Bilateral Deep Brain Stimulation.

Background: We report a patient with bilateral HT treated with DBS. Case report: A 58-year-old man diagnosed with HIV/AIDS and progressive multifocal leukoencephalopathy (PML) presented with 20 years of bilateral arm tremor refractory to therapy. DBS was implanted on the left ventral intermediate nucleus and posterior subthalamic area (VIM/PSA). One year later, a right VIM/PSA DBS was implanted. At twelve months, there were no significant side-effects. With his DBS turned off and on, the Fahn-Tolosa-Marin scale was rated 82 and 58, respectively. Discussion: To our knowledge, this is the first report of bilateral DBS VIM/PSA treating HT with no significant side effects. Highlights: We report a successful treatment using deep brain stimulation of bilateral Holmes tremor that was caused by progressive multifocal encephalopathy. The patient achieved 30% improvement in tremor control with a meaningful improvement in his activities of daily living.

Pain paths among post-COVID-19 condition subjects: A prospective cross-sectional study with in-person evaluation.

BACKGROUND: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. METHODS: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. RESULTS: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. CONCLUSIONS: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. SIGNIFICANCE: COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.

Treatment of segmental continuous hypertrophic myokymia of the limb with botulinum A toxin.

Myokymia is defined as fluctuating hyperexcitability of muscle fibers caused by repetitive spontaneous contraction of motor units. Myokymia is generally benign with self-resolution, although symptomatic treatment with benzodiazepines, anticonvulsants, and muscle relaxants can be used. Botulinum toxins can also be utilized, although they are mostly used for symptomatic facial myokymia. Here, we report two patients who developed continuous myokymia, resulting in secondary hypertrophy, stiffness, and discomfort in the affected muscles. The first patient had a history of a tethered spinal cord and developed continuous myokymia in the S1 and S2 radicular regions of the left leg. The second patient underwent radiation therapy for lung cancer and developed brachial plexopathy with abnormal activity in the muscles supplied by the musculocutaneous nerve in the right arm. Both patients experienced sleep disturbance, focal discomfort, and restlessness. The anticonvulsants and muscle relaxants were ineffective. Chemodenervation with botulinum A toxin was initiated using either onabotulinumtoxinA or abobotulinumtoxinA. Both patients experienced a substantial reduction in myokymia, with ongoing reversal of muscle hypertrophy and significant improvement in reported subjective symptoms. Treatment with botulinum toxins can be highly effective in patients with symptomatic segmental continuous hypertrophic myokymia and may be considered first-line therapy.

Advance Directive and POLST Documentation in Decedents With Dementia at a Memory Care Center: The Importance of Early Advance Care Planning.

Background and Objectives: To determine the frequency of and challenges to documentation of advance care planning (ACP) in people with dementia, we conducted a chart review of 746 deceased patients seen at a tertiary memory care center between 2012 and 2017. Methods: The rates of documented advance directives (ADs), Physician Order for Life-Sustaining Treatment (POLST), and Do Not Resuscitate (DNR) status were calculated from review of institutional electronic health records. Regression analysis was used to determine associations between ACP documentation and patient characteristics. Results: At the time of death, approximately half of the patients had a documented AD and/or DNR status and 37% had a documented POLST; 30% of patients did not have any ACP documentation. Whereas most of the ADs were documented more than 5 years before time of death, POLST and DNR status were documented more frequently within 2 years of time of death. People who presented to clinic at a younger age and who primarily spoke English were more likely to have documented ADs. People living in zip codes with lower household incomes were 2-4.5 times less likely to have a POLST or DNR documentation. Discussion: ACP is underutilized in people with dementia, even among those seen in a specialty memory care center. ACP should be introduced early on for people with dementia to ensure patients have a voice in their care.

The prevalence of skin tears and associated factors in hospitalised patients with cancer.

OBJECTIVE: Oncology patients are vulnerable to skin breakdown. The primary purpose of this study was to estimate the prevalence of skin tears (STs) in hospitalised patients with cancer and to explore related sociodemographic and clinical factors. METHOD: This was an observational, epidemiological, cross-sectional study conducted in an oncology hospital in the city of São Paulo. All STs were classified using the STAR Classification adapted and validated for Brazil. RESULTS: Of the 341 patients evaluated, 22 had STs, equating to a prevalence of 6.5%. A higher number of STs were noted on the lower limbs (26.9%) than on other body areas. The main factors associated with STs were the use of anticoagulants, the presence of ecchymosis and the use of incontinence briefs. CONCLUSION: This study contributed to a better understanding of the epidemiology of STs in hospitalised patients with cancer, as well as its associated factors. Results may inform nursing professionals with regard to the need to develop prevention strategies and early interventions.

Characteristics of people with dementia lost to follow-up from a dementia care center.

OBJECTIVE: To identify the prevalence and characteristics of people living with dementia (PLWD) lost to follow-up (LTFU) from a specialized dementia care clinic and to understand factors influencing patient follow-up status. METHODS: We conducted a retrospective chart review of PLWD seen at a dementia care clinic 2012-2017 who were deceased as of 2018 (n = 746). Participants were evaluated for follow-up status at the time of death. Generalized linear regression was used to analyze demographic and diagnostic characteristics by follow-up status. Text extracted from participant medical records was analyzed using qualitative content analysis to identify reasons patients became LTFU. RESULTS: Among PLWD seen at a dementia care clinic, 42% became LTFU before death, 39% of whom had chart documentation describing reasons for loss to follow-up. Increased rates of LTFU were associated with female sex (risk ratio 1.27, [95% confidence interval 1.09-1.49]; p = 0.003), educational attainment of high school or less (1.34, [1.13-1.61]; p = 0.001), and death in a long-term care facility (1.46, [1.19-1.80]; p = 0.003). Commonly documented reasons for not returning for care at the clinic included switching care to another provider (42%), logistical difficulty accessing care (26%), patient-family decision to discontinue care (24%), and functional challenges in accessing care (23%). CONCLUSIONS: PLWD are LTFU from specialized memory care at high rates. Attention to care coordination, patient-provider communication, and integrated use of alternative care models such as telehealth are potential strategies to improve care.

Acute skin failure e lesão por pressão em paciente com covid-19 / Acute skin failure and pressure injury in the patient with covid-19 / Acute skin failure y lesión por presión en el paciente con covid-19

Objetivo:relatar o caso de um paciente crítico com COVID-19 e mostrar os principais achados relacionados à lesão considerada Acute skin failure (ASF), bem como realizar seu diagnóstico diferencial com lesão por pressão (LP) evitável. Método: estudo observacional do tipo relato de caso, desenvolvido em um hospital de São Paulo, na unidade de terapia intensiva (UTI) exclusiva a pessoas diagnosticadas com COVID-19. Os dados foram coletados de um único paciente, entre os meses de março e setembro de 2020. Resultados: paciente com complicações da COVID-19 evoluiu com lesão de pele, inicialmente definida como LP e posteriormente reclassificada como ASF. Os seguintes achados corroboraram o diagnóstico: ventilação mecânica invasiva prolongada, insuficiências respiratória, renal e cardíaca e sepse de foco respiratório. Além disso, outros fatores agravantes, como o uso de droga vasoativa, instabilidade hemodinâmica com intolerância ao mínimo reposicionamento, jejum prolongado e coagulopatia intravascular disseminada associada à infecção pelo coronavírus. Conclusão: o relato mostra que existem dificuldades para o diagnóstico diferencial entre ASF e LP na prática clínica. Trata-se de conceito novo, sendo fundamental que o profissional de saúde reconheça os principais fatores associados ao aparecimento da ASF, muitos dos quais também estão relacionados ao desenvolvimento das LP, ressaltando a necessidade de análise individualizada dessas lesões, e garantia da implementação de intervenções adequadas para prevenção e tratamento.

Objective:report the case of a critical patient with COVID-19 and show the main findings related to the injury considered acute skin failure (ASF), as well as perform his differential diagnosis with preventable pressure injury (PI). Method: observational, longitudinal, case report type study, developed in a hospital in São Paulo, in the intensive care unit (ICU) exclusively for people diagnosed with COVID-19. Data were collected from a single patient between March and September 2020. Results: A patient with complications from COVID-19 developed a skin lesion, initially defined as PI and later reclassified as ASF. The following findings corroborated the diagnosis: prolonged invasive mechanical ventilation, respiratory, renal and cardiac insufficiency and sepsis of respiratory focus. In addition, other aggravating factors, such as the use of vasoactive drugs, hemodynamic instability with intolerance to minimal repositioning, prolonged fasting and disseminated intravascular coagulopathy associated with coronavirus infection. Conclusion: the report shows that there are difficulties for the differential diagnosis between ASF and PI in clinical practice. This is a new concept, and it is essential that health professionals recognize the main factors associated with the appearance of ASF, many of which are also related to the development of PI, highlighting the need for individualized analysis of these injuries, and ensuring the implementation of interventions for prevention and treatment

Objetivo:Informar los principales hallazgos en un paciente con COVID-19 ingresado en una unidad de cuidados intensivos (UCI), que desarrolló una lesión considerada Insuficiencia cutánea aguda (PPA), así como diferenciar la lesión por presión (LP) de la PPA. Método: estudio observacional, longitudinal y descriptivo, del tipo reporte de caso, desarrollado en un hospital de São Paulo, en la UCI exclusivamente para personas diagnosticadas con COVID-19, entre los meses de marzo a septiembre de 2020. La muestra estuvo conformada por un paciente. Resultados: Un paciente con complicaciones por COVID-19, evoluciona con una lesión cutánea, inicialmente definida como LP, sin embargo, reclasificada como ASK. Los hallazgos que corroboran el diagnóstico fueron: Ventilación mecánica invasiva prolongada, insuficiencia respiratoria, renal y cardíaca y sepsis del foco respiratorio. Además, factores agravantes como el uso de fármacos vasoactivos, inestabilidad hemodinámica con intolerancia al reposicionamiento mínimo, ayuno prolongado, história clínica con varias comorbilidades y coagulopatía intravascular diseminada inducida por infección por coronavirus. Conclusión: El informe muestra que existen dificultades para el diagnóstico diferencial entre PPA y PL en la práctica clínica. Es un concepto novedoso, y es fundamental que el profesional de la salud reconozca los principales factores asociados a la aparición de la PPA, muchos de los cuales también están relacionados con el desarrollo de LP, destacando la necesidad de un análisis individualizado de estas lesiones y asegurando la implementación de intervenciones adecuadas, para la prevención y el tratamiento

Terapia tópica para el tratamiento del dolor en heridas neoplásicas malignas: protocolo de revisión de alcance.

BACKGROUND: A total of 14.5% of cancer patients develop malignant neoplastic wounds (MNW), characterised as friable, exudative, fetid, bleeding, and painful. Some studies report that all patients with MNW experience pain, but there is lack of scientific evidence to support their treatment. OBJECTIVE: To map and examine the existing evidence on topical therapies to manage pain in adult patients with MNW. METHOD: A scoping review protocol was designed, according to the Joanna Briggs Institute (JBI) methodology. The databases CINAHL, LILACS, Embase, Scopus, Web of Science, PubMed, Cochrane, NICE, Scopus, JBISRIR and the grey literature, for searching published and unpublished studies in English, Portuguese and Spanish. The selection will be made by at least two reviewers. The summary of the results will be narrative, with graphs and tables. Qualitative and quantitative studies and reviews will be included, describing the use of topical pain therapies in patients with MNW. CONCLUSION: This study will allow to classify and discuss the available topical therapies, and to recommend future primary studies.

INTRODUCCIÓN: El 14,5% de los pacientes con cáncer desarrolla heridas neoplásicas malignas (HNM), caracterizadas como friables, exudativas, fétidas, sangrantes y dolorosas. Algunos estudios reportan que todos los pacientes con HNM experimentan dolor, pero hay escasez de evidencia científica para fundamentar su tratamiento. OBJETIVO: Mapear y examinar la evidencia existente sobre terapias tópicas para manejar el dolor en pacientes adultos con HNM. MÉTODO: Se diseñó un protocolo de revisión de alcance, de acuerdo con la metodología del Joanna Briggs Institute (JBI). Serán consultadas las bases de datos CINAHL, LILACS, Embase, Scopus, Web of Science, PubMed, Cochrane, NICE, Scopus, JBISRIR y la literatura gris, para la búsqueda de estudios publicados y no publicados en inglés, portugués y español. La selección estará a cargo de, al menos, dos revisores. La síntesis de los resultados será narrativa, con gráficos y tablas. Se incluirán estudios cualitativos, cuantitativos y revisiones, que describan el uso de terapias tópicas para el dolor en pacientes con HNM. CONCLUSIÓN: Este estudio permitirá clasificar y discutir las terapias tópicas disponibles, y recomendar futuros estudios primarios.

Connections Between Insomnia and Cognitive Aging.

Insomnia is a common sleep disorder among older adults, and a risk factor for poor physical and mental health. However, the relationship between insomnia and cognitive health is not well understood. Here, we review observational studies that have investigated whether insomnia is associated with deficits in objective cognitive performance and an increased risk of dementia, magnetic resonance imaging studies that have assessed grey matter volumes and white matter microstructure, and interventional studies that have explored whether the treatment of insomnia can improve cognitive outcomes. There are inconsistent findings regarding impaired performance in objective cognitive tests and reduced grey matter volumes, and limited, emerging, evidence that suggests that insomnia is associated with an increased risk of dementia and reduced white matter integrity. Although the interventional literature is still in its infancy, there is some indication that treatment may have an impact on vigilance. Well-powered studies examining sources of heterogeneity are warranted.

Facebook como meio de divulgação científica: aliado ou inimigo? / Facebook as a means of scientific promotion: ally or enemy?

Diferentes estratégias para divulgação de uma nova ferramenta de comunicação e interação em saúde, voltada para pessoas com deficiência, foram aplicadas no Facebook® com o objetivo de identificar quais estratégias de divulgação aplicadas ao Facebook® promoveram mais acessos à rede social D Eficiência e caracterizar seus usuários. Estudo quantitativo, descritivo e longitudinal, com dados extraídos do gerenciador de métricas do Facebook®. A divulgação com busca ativa foi superior a passiva, sendo responsável por 91,4% (n=4.519) dos acessos, via celular (71%) por mulheres (81%). Publicações com hiperlink e imagens foram mais engajadoras. O Facebook® mostrou-se como uma ferramenta eficaz por atingir números expressivos de pessoas, e deve ser considerado na divulgação de novas tecnologias. Para tal, é necessário criar conteúdos atrativos e busca ativa de usuários. Estudos complementares devem continuar a avaliação dessa estratégia, com análise da divulgação orgânica e divulgação com impulsionamento pago.

Different strategies for promoting a new health communication and interaction tool, aimed at persons with disabilities, were applied on Facebook® in order to identify which promotion strategies promoted hits to the D Eficiência social network, and to characterize its users. Quantitative, descriptive and longitudinal study, with data extracted from the Facebook® metrics manager. Active search promotion was higher than passive promotion, accounting for 91.4% (n=4,519) of hits, via cell phone (71%) by women (81%). Hyperlinked publications and images were more engaging. Facebook® proved to be an effective tool for reaching significant numbers of people and should be considered in the promotion of new technologies. For this, it is necessary to create attractive content and conduct an active search for users. Complementary studies should continue to evaluate this strategy, with analysis of organic promotion and paid promotion.

Effect of Collaborative Dementia Care via Telephone and Internet on Quality of Life, Caregiver Well-being, and Health Care Use: The Care Ecosystem Randomized Clinical Trial.

Importance: Few health systems have adopted effective dementia care management programs. The Care Ecosystem is a model for delivering care from centralized hubs across broad geographic areas to caregivers and persons with dementia (PWDs) independently of their health system affiliations. Objective: To determine whether the Care Ecosystem is effective in improving outcomes important to PWDs, their caregivers, and payers beyond those achieved with usual care. Design, Setting, and Participants: A single-blind, randomized clinical trial with a pragmatic design was conducted among PWDs and their caregivers. Each PWD-caregiver dyad was enrolled for 12 months between March 20, 2015, and February 28, 2017. Data were collected until March 5, 2018. Study interventions and assessments were administered over the telephone and internet by clinical and research teams in San Francisco, California, and Omaha, Nebraska. Of 2585 referred or volunteer PWD-caregiver dyads in California, Iowa, or Nebraska, 780 met eligibility criteria and were enrolled. A total of 512 PWD-caregiver dyads were randomized to receive care through the Care Ecosystem and 268 dyads to receive usual care. All eligible PWDs had a dementia diagnosis; were enrolled or eligible for enrollment in Medicare or Medicaid; and spoke English, Spanish, or Cantonese. Analyses were intention-to-treat. Intervention: Telephone-based collaborative dementia care was delivered by a trained care team navigator, who provided education, support and care coordination with a team of dementia specialists (advanced practice nurse, social worker, and pharmacist). Main Outcomes and Measures: Primary outcome measure: Quality of Life in Alzheimer's Disease based on caregiver's rating of 13 aspects of PWD's well-being (including physical health, energy level, mood, living situation, memory, relationships, and finances) on a 4-point scale (poor to excellent). Secondary outcomes: frequencies of PWDs' use of emergency department, hospitalization, and ambulance services; caregiver depression (score on 9-Item Patient Health Questionnaire; higher scores indicate more severe depression); and caregiver burden (score on 12-Item Zarit Burden Interview; higher scores indicate more severe caregiver burden). Results: The 780 PWDs (56.3% female; mean [SD] age, 78.1 [9.9] years) and 780 caregivers (70.9% female; mean [SD] age, 64.7 [12.0] years) lived in California (n = 452), Nebraska (n = 284), or Iowa (n = 44). Of 780 dyads, 655 were still active at 12 months, and 571 completed the 12-month survey. Compared with usual care, the Care Ecosystem improved PWD quality of life (B, 0.53; 95% CI, 0.25-1.30; P = .04), reduced emergency department visits (B, -0.14; 95% CI, -0.29 to -0.01; P = .04), and decreased caregiver depression (B, -1.14; 95% CI, -2.15 to -0.13; P = .03) and caregiver burden (B, -1.90; 95% CI, -3.89 to -0.08; P = .046). Conclusions and Relevance: Effective care management for dementia can be delivered from centralized hubs to supplement usual care and mitigate the growing societal and economic burdens of dementia. Trial Registration: ClinicalTrials.gov identifier: NCT02213458.

Formulation, Development and Scale-Up of Fixed-Dose Combination Tablets Containing Zidovudine, Lamivudine and Nevirapine.

BACKGROUND: The development of antiretroviral associations in a single dosage form aims to ensure improved efficacy, low costs and better adherence to treatment. OBJECTIVE: This work performed the pharmacotechnical development, coating, and stability studies of fixed-dose combination tablets of zidovudine, lamivudine and nevirapine (300 + 200 + 150 mg, respectively). METHODS: Qualitative and quantitative planning of diluents (101 and 250 microcrystalline cellulose, spray-dried monohydrate lactose and corn starch) and coating polymers (Opadry white II HP® and Instacoat Aqua Moistshield II®) were analyzed, and direct compression (DC) and wet granulation (WG) methods were tested aiming the development of the pharmaceutical form. Quality control was carried out according to the specifications set by official compendia. The chosen formulation was scaled-up and the industrial batches were submitted to accelerated and long-term stability studies. RESULTS: The batches obtained by WG met the requirements, using 101 microcrystalline cellulose, corn starch and Opadry white II HP® as excipients. The DC trial was not possible due to the need of a greater ratio of excipients to improve formulation properties. CONCLUSION: Thus, this study brings a new therapeutic alternative for HIV treatment, contributing to the development of another possibility to simplify drug administration.

Variations in Costs of a Collaborative Care Model for Dementia.

OBJECTIVES: Care coordination programs can improve patient outcomes and decrease healthcare expenditures; however, implementation costs are poorly understood. We evaluate the direct costs of implementing a collaborative dementia care program. DESIGN: We applied a micro-costing analysis to calculate operational costs per-participant-month between March 2015 and May 2017. SETTING: The University of California, San Francisco (UCSF) and the University of Nebraska Medical Center (UNMC). PARTICIPANTS: Participants diagnosed with dementia, enrolled in Medicare or Medicaid, 45 years of age or older, residents of California, Nebraska or Iowa, and having a caregiver. The sample was 272 (UCSF) and 192 (UNMC) participants. INTERVENTION: A collaborative dementia care program provided by care team navigators (CTNs), advanced practice nurses, a social worker, and a pharmacist, focusing on caregiver support and education, medications, advance care planning, and behavior symptom management. MEASUREMENTS: We measured costs (personnel, supplies, equipment, and training costs) during three program periods, Start-up, Early Operations, and Continuing Operations, and estimated the effects of caseload variation on costs. RESULTS: Start-up and Early Operations costs were, respectively, $581 and $328 (California), and $501 and $219 (Nebraska) per-participant-month. Average costs decreased across phases to $241 (California) and $142 (Nebraska) per-participant-month during Continuing Operations. We estimated that costs would range between $75 (UNMC) and $92 (UCSF) per-participant-month with the highest projected caseloads (90). CONCLUSION: We found that CTN caseload is an important driver of service cost. We provide strategies for maximizing caseload without sacrificing quality of care. We also discuss current barriers to broad implementation that can inform new reimbursement policies. J Am Geriatr Soc 67:2628-2633, 2019.

The Effect of Sedating Agents on Drug-Induced Sleep Endoscopy Findings.

OBJECTIVE: Drug-induced sleep endoscopy (DISE) has gained interest for upper airway evaluation in patients with snoring and obstructive sleep apnea (OSA), and different drugs have been used to induce sedation. Nevertheless, all drugs have presented specific advantages and disadvantages with differential effects on respiratory physiology. This study evaluated and compared the effects of midazolam, propofol and dexmedetomidine on DISE findings, O2 nadir, and bispectral index (BIS) in the same sample of patients. STUDY DESIGN: Case series prospective study. METHODS: Consecutive patients who elected to undergo surgery for OSA treatment and were intolerant to conservative therapies underwent DISE with propofol, dexmedetomidine, and midazolam between July 2015 and July 2016. RESULTS: Fifty-two patients were analyzed, and 43 (82.7%) were men. Agreement among drugs for both degree and patterns of obstruction was excellent at all sites (velum, oropharynx, and epiglottis) except for the tongue base. Dexmedetomidine had the least complete collapse sites and highest O2 nadir and was the only drug for which apnea severity and obstruction levels (upper, lower, or combined) were correlated. The variability among drug treatments for the BIS index was considerable, and propofol had the lowest variability and average value. CONCLUSION: Drug selection had a relevant influence in DISE findings. Compared with dexmedetomidine, midazolam and propofol presented higher incidence of tongue base collapse, lower O2 levels, and lower BIS index values. Propofol resulted in an O2 nadir that most resembled that observed during polysomnography. The BIS index variability differed among drugs, and its use was considered relevant for sedation orientation. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:506-513, 2019.

Digital Health and Sleep-Disordered Breathing: A Systematic Review and Meta-Analysis.

STUDY OBJECTIVES: Sleep disorders in most individuals remain undiagnosed and without treatment. The use of novel tools and mobile technology has the potential to increase access to diagnosis. The objective of this study was to perform a quantitative and qualitative analysis of the available literature evaluating the accuracy of smartphones and portable devices to screen for sleep-disordered breathing (SDB). METHODS: A literature review was performed between February 18, 2017 and March 15, 2017. We included studies evaluating adults with SDB symptoms through the use mobile phones and/or portable devices, using standard polysomnography as a comparison. A qualitative evaluation of studies was performed with the QUADAS-2 rating. A bivariate random-effects meta-analysis was used to obtain the estimated sensitivity and specificity of screening SDB for four groups of devices: bed/mattress-based, contactless, contact with three or more sensors, and contact with fewer than three sensors. For each group, we also reported positive predictive values and negative predictive values for mild, moderate, and severe obstructive sleep apnea (OSA) screening. RESULTS: Of the 22 included studies, 18 were pooled in the meta-analysis. Devices that were bed/mattress-based were found to have the best sensitivity overall (0.921, 95% confidence interval [CI] 0.870, 0.953). The sensitivity of contactless devices to detect mild OSA cases was the highest of all groups (0.976, 95% CI 0.899, 0.995), but provided a high false positive rate (0.487, 95% CI 0.137, 0.851). The remaining groups of devices showed low sensitivity and heterogeneous results. CONCLUSIONS: This study evidenced the limitations and potential use of portable devices in screening patients for SDB. Additional research should evaluate the accuracy of devices when used at home.

Intermittent Catheterization and Urinary Tract Infection: A Comparative Study Between Germany and Brazil.

PURPOSE: The purpose of this study was to describe and compare factors that affect urinary tract infection (UTI) rates in people with spina bifida (SB) and neurogenic bladder dysfunction before and following initiation of intermittent catheterization (IC). DESIGN: A quantitative, descriptive, correlational study. SUBJECTS AND SETTING: The study included people who were from Germany, a high-income nation, and Brazil, a middle-income nation. Brazilian participants were recruited from a public rehabilitation hospital in the state of Minas Gerais. German participants were drawn from different regions of the country. The study sample included 200 participants; participants were either individuals diagnosed with SB and neurogenic bladder dysfunction and using IC, or caregivers of persons using IC for bladder management. METHODS: Data were collected through a survey questionnaire developed for urological follow-up of SB patients. A translated and validated version of the form was used to collect data in Germany. To evaluate annual episodes of UTI, we considered the number of symptomatic UTI before and after IC. RESULTS: Participants from Brazil were significantly younger than German patients (median age 9 vs 20 years, P < .001). Brazilians predominately used assisted catheterization (63.0%), whereas most Germans performed self-catheterization (61.0%). Use of IC greatly reduced the incidence of UTI in both groups (mean 2.8 episodes per year before IC vs mean 1.1 episodes after starting IC, P < .001). Women had a higher number of UTI, both before and after IC, but enjoyed greater reduction in UTI after initiating IC than men. Self-catheterization also promoted a greater reduction of UTI than assisted IC (P = .022). CONCLUSIONS: Intermittent catheterization reduced annual episodes of UTI in both samples despite differences in catheterization technique. Patients practicing and performing self-catheterization achieved a greater reduction than those who relied on assisted IC. Comparative studies among additional countries with varying median income levels are needed to better understand the needs of individuals with SB and their families, and to plan and implement safe nursing interventions.

Integrating the Divided Nasal Cannula Into Routine Polysomnography to Assess Nasal Cycle: Feasibility and Effect on Outcomes.

STUDY OBJECTIVES: Patients suspected to have sleep-disordered breathing underwent an overnight polysomnography using a divided nasal cannula to gain additional information about the nasal cycle during sleep. METHODS: This was a prospective, observational cohort study replacing the undivided nasal cannula with a divided nasal cannula during routine polysomnography (n = 28). RESULTS: Integration of the divided nasal cannula pressure transducer system into routine polysomnography was easy and affordable. Most patients (89%) demonstrated nasal cycle changes during the test. Nasal cycle changes tended to occur during body position changes (62%) and transitions from non-rapid eye movement sleep to rapid eye movement sleep (41%). The mean nasal cycle duration was 2.5 ± 2.1 hours. Other sleep study metrics did not reveal statistically significant findings in relation to the nasal cycle. CONCLUSIONS: Replacing an undivided nasal cannula with a divided nasal cannula is easy to implement, adding another physiologic measure to polysomnography. Although the divided nasal cannula did not significantly affect traditional polysomnographic metrics such as the apnea-hypopnea index or periodic limb movement index based on this small pilot study, we were able to replicate past nasal cycle findings that may be of interest to sleep clinicians and researchers. Given the ease with which the divided nasal cannula can be integrated, we encourage other sleep researchers to investigate the utility of using a divided nasal cannula during polysomnography.