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In response to a statewide stay-at-home order during the COVID-19 pandemic, the Seniors Clinic launched an interprofessional student-led, telephone-based outreach initiative targeting older adults deemed high risk for social isolation. The initiative primarily aimed to enhance students' geriatric and interprofessional education during a time when clinical learning opportunities were limited, as well as supporting geriatric patients and providers through outreach during the COVID-19 quarantine period. Nurse practitioner, medical, and pharmacy students participated in virtual patient contact, geriatric case-based learning, and team-based interprofessional development. We conducted pre-and post-outreach assessments with students and geriatric providers to determine the effects of this initiative. After participating in the 3-month outreach initiative, interprofessional students reported increased confidence in conducting outreach calls, participating in interdisciplinary team discussions, and reviewing geriatric cases. This student-led telephone-based outreach to older adults improved students' exposure to and confidence with interprofessional teamwork and geriatric medicine. Our experience can inform future interprofessional initiatives to improve outreach to populations affected by public health emergencies.
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COVID-19 , Geriatria , Idoso , Geriatria/educação , Humanos , Relações Interprofissionais , Pandemias , Equipe de Assistência ao Paciente , SARS-CoV-2 , EstudantesRESUMO
Background: Methenamine is a drug used for the prevention of lower urinary tract infections (UTIs). However, efficacy has not been established in older adults or patients with varying degrees of kidney function. Objective: To evaluate the effectiveness of methenamine for the prevention of UTI in adults 60 years and older. Methods: This was a retrospective, pre-post, observational study. The study included primary care patients 60 years and older who were taking methenamine between January 1, 2015, and September 30, 2018. The primary outcome was the time to first UTI after methenamine initiation compared with the average time between UTIs in the 12 months prior to methenamine initiation. Results: Of 434 patients reviewed, 150 met inclusion criteria. The average time to UTI was 3.3 months prior to methenamine initiation compared with 5.5 months after methenamine initiation (P = 0.0004). There were 33 patients (22%) who did not have a UTI after methenamine initiation. Also, 14 patients (9.3%) had a calculated CrCl <30 mL/min at baseline. The average time to UTI in these patients was 3.3 months prior to methenamine initiation compared with 12.7 months after initiation (P < 0.0001). Conclusion and Relevance: Methenamine use was associated with a longer time to UTI in older adults with varying degrees of kidney function. The effectiveness of methenamine appeared to be similar regardless of kidney function, which is new evidence. Because of a lack of acquired resistance, methenamine may be an effective option for UTI prophylaxis in older adults.
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Anti-Infecciosos Urinários/uso terapêutico , Metenamina/uso terapêutico , Infecções Urinárias/prevenção & controle , Idoso , Feminino , Humanos , Testes de Função Renal , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Many biodiversity-ecosystem services studies omit cultural ecosystem services (CES) or use species richness as a proxy and assume that more species confer greater CES value. We studied wildflower viewing, a key biodiversity-based CES in amenity-based landscapes, in Southern Appalachian Mountain forests and asked (i) How do aesthetic preferences for wildflower communities vary with components of biodiversity, including species richness?; (ii) How do aesthetic preferences for wildflower communities vary across psychographic groups?; and (iii) How well does species richness perform as an indicator of CES value compared with revealed social preferences for wildflower communities? Public forest visitors (n = 293) were surveyed during the summer of 2015 and asked to choose among images of wildflower communities in which flower species richness, flower abundance, species evenness, color diversity, and presence of charismatic species had been digitally manipulated. Aesthetic preferences among images were unrelated to species richness but increased with more abundant flowers, greater species evenness, and greater color diversity. Aesthetic preferences were consistent across psychographic groups and unaffected by knowledge of local flora or value placed on wildflower viewing. When actual wildflower communities (n = 54) were ranked based on empirically measured flower species richness or wildflower viewing utility based on multinomial logit models of revealed preferences, rankings were broadly similar. However, designation of hotspots (CES values above the median) based on species richness alone missed 27% of wildflower viewing utility hotspots. Thus, conservation priorities for sustaining CES should incorporate social preferences and consider multiple dimensions of biodiversity that underpin CES supply.
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Estética/psicologia , Flores , Biodiversidade , Comportamento de Escolha , Conservação dos Recursos Naturais , Ecossistema , Florestas , Humanos , Dinâmica PopulacionalRESUMO
Rural landscapes face changing climate, shifting development pressure, and loss of agricultural land. Perennial bioenergy crops grown on existing agricultural land may provide an opportunity to conserve rural landscapes while addressing increased demand for biofuels. However, increased bioenergy production and changing land use raise concerns for tradeoffs within the food-energy-environment trilemma. Heterogeneity of climate, soils, and land use complicate assessment of bioenergy potential in complex landscapes, creating challenges to evaluating future tradeoffs. The hypothesis addressed herein is that perennial bioenergy production can provide an opportunity to avoid agricultural land conversion to development. Using a process-based crop model, we assessed potential bioenergy crop growth through 2100 in a southern Appalachian Mountain region and asked: (1) how mean annual yield differed among three crops (switchgrass Panicum virgatum, giant miscanthus Miscanthus x giganteus, and hybrid poplar Populus x sp.) under current climate and climate change scenarios resulting from moderate and very high greenhouse gas emissions; (2) how maximum landscape yield, spatial allocation of crops, and bioenergy hotspots (areas with highest potential yield) varied among climate scenarios; and (3) how bioenergy hotspots overlapped with current crop production or lands with high development pressure. Under both climate change scenarios, mean annual yield of perennial grasses decreased (-4% to -39%), but yield of hybrid poplar increased (+8% to +20%) which suggests that a switch to woody crops would maximize bioenergy crop production. In total, maximum landscape yield increased by up to 90 000 Mg/yr (6%) in the 21st century due to increased poplar production. Bioenergy hotspots (> 18 Mg x ha(-1) x yr(-1)) consistently overlapped with high suburban/exurban development likelihood and existing row crop production. If bioenergy production is constrained to marginal (non-crop) lands, landscape yield decreased by 27%. The removal of lands with high development probability from crop production resulted in losses of up to 670 000 Mg/yr (40%). This study demonstrated that tradeoffs among bioenergy production, crop production, and exurban expansion in a mountainous changing rural landscape vary spatially with climate change over time. If markets develop, bioenergy crops could potentially counter losses of agricultural land to development.
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Biocombustíveis , Mudança Climática , Conservação dos Recursos Naturais , Produtos Agrícolas , Ecossistema , Agricultura , North CarolinaRESUMO
Plant invasions can alter the quality and quantity of detrital and root-derived inputs entering a system, thereby influencing the activities of microbial decomposers and affecting the soil carbon cycle. The effect of these inputs on soil carbon storage is often conflicting, suggesting strong context dependency in the plant-decomposer relationship. Whether there is a generalizable pattern that explains this dependency remains relatively unexplored. Here, we (1) examine how invasion by the exotic grass Microstegium vimineum affects carbon cycling across a land use gradient, and (2) evaluate the importance of inorganic nitrogen availability and other environmental variables for explaining patterns in soil carbon. Using paired invaded and uninvaded plots, we quantified invasion effects on belowground carbon pools, extracellular enzyme activities, and native leaf litter decomposition in forests embedded in an urban, agricultural, or forested landscape matrix. Compared to the urban matrix, invasion-associated declines in total soil organic carbon in the forested and agricultural landscapes were 3.5 and 2.5 times greater, respectively. Inorganic nitrogen availability and M. vimineum biomass interacted to explain these patterns: when both nitrogen availability and M. vimineum biomass were high, invaded soils exhibited higher total organic carbon, unchanged particulate organic matter carbon, and higher mineral-associated organic matter carbon compared to adjacent uninvaded soils. Consistent with these patterns, activities of carbon-mineralizing enzymes were lower in invaded than in uninvaded soils when both nitrogen availability and M. vimineum biomass were high. By contrast,. decomposition of native leaf litter was faster when inorganic nitrogen availability and M. vimineum biomass were high. Our findings suggest that, although this invader may accelerate carbon cycling in forest soils, its effects on soil carbon storage largely depend on nitrogen availability and invader biomass, which can be altered by landscape-level patterns of land use. Additional research is needed to determine whether land use or other broad-scale processes such as atmospheric nitrogen deposition can explain context dependence in plant invasion effects on other ecosystem processes.
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Carbono/química , Florestas , Espécies Introduzidas , Poaceae/fisiologia , Solo/química , Biodegradação Ambiental , Folhas de Planta , Poaceae/classificaçãoRESUMO
The behavior of long-distance migrants during stopover is constrained by the need to quickly and safely replenish energetic reserves. Replenishing fuel stores at stopover sites requires adjusting to unfamiliar landscapes with little to no information about the distribution of resources. Despite their critical importance to the success of songbird migration, the effects of landscape composition and configuration on fuel deposition rates (FDR [g/d]), the currency of migration, has not been tested empirically. Our objectives were to understand the effects of heterogeneous landscapes on FDR of forest-dwelling songbirds during spring migration. The results of field experiments were used to parameterize a spatially explicit, individual-based model of forest songbird movement and resulting FDR. Further field experiments were used to validate the results from the individual-based model. In simulation experiments, we altered a Gulf South landscape in a factorial design to predict the effects of future patterns under different scenarios of land use change in which the abundance of high-quality hardwood habitat and the spatial aggregation of habitat varied. Simulated FDR decreased as the amount of hardwood in the landscape decreased from 41% to 22% to 12%. Further, migrants that arrived in higher-quality habitat types gained more mass. Counter to our expectations, FDR was higher with lower spatial aggregation of habitat. Differences in refueling rates may be most influenced by whether or not an individual experiences an initial searching cost after landing in poor-quality habitat. Therefore, quickly locating habitat with sufficient food resources at each stopover may be the most important factor determining a successful migration. Our findings provide empirical evidence for the argument that hardwood forest cover is a primary determinant of the quality of a stopover site in this region. This study represents the first effort to empirically quantify FDRs based on the configuration of landscapes.
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Migração Animal , Ecossistema , Modelos Biológicos , Aves Canoras/fisiologia , Animais , Monitoramento Ambiental , Louisiana , Mississippi , Reprodutibilidade dos TestesRESUMO
Land-use dynamics and climatic gradients have large effects on many terrestrial systems. Exurban development, one of the fastest growing forms of land use in the United States, may affect wildlife through habitat fragmentation and building presence may alter habitat quality. We studied the effects of residential development and temperature gradients on bird species occurrence at 140 study sites in the southern Appalachian Mountains (North Carolina, U.S.A.) that varied with respect to building density and elevation. We used occupancy models to determine 36 bird species' associations with building density, forest canopy cover, average daily mean temperature, and an interaction between building density and mean temperature. Responses varied with habitat requirement, breeding range, and migration distance. Building density and mean temperature were both included in the top occupancy models for 19 of 36 species and a building density by temperature interaction was included in models for 8 bird species. As exurban development expands in the southern Appalachians, interior forest species and Neotropical migrants are likely to decline, but shrubland or edge species are not likely to benefit. Overall, effects of building density were greater than those of forest canopy cover. Exurban development had a greater effect on birds at high elevations due to a greater abundance of sensitive forest-interior species and Neotropical migrants. A warming climate may exacerbate these negative effects.
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Aves/fisiologia , Ecossistema , Temperatura , Migração Animal , Animais , Região dos Apalaches , Cruzamento , Conservação dos Recursos Naturais , Modelos Teóricos , North Carolina , Dinâmica PopulacionalRESUMO
Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated cardiovascular benefits in patients with heart failure, many of which take loop diuretics. There are no evidence-based recommendations identifying which patients may require loop diuretic dose decreases or how to adjust loop diuretic doses when SGLT2is are initiated. Objectives: The main objective of this study was to investigate the frequency and degree of adjustments in loop diuretic doses after SGLT2i initiation in patients with heart failure. Methods: In this retrospective evaluation, patients seen in the UCHealth system with a diagnosis of heart failure who were prescribed a loop diuretic before initiation of SGLT2i were identified. We described loop diuretic dose changes at the time of SGLT2i initiation, at 6 months after initiation, and at 1 year after initiation. We also described de-escalation of maintenance medications that can contribute to hypotension at these time points. Data were evaluated using descriptive statistics. Results: A total of 100 patients were included. Loop diuretic dose was reduced empirically upon SGLT2i initiation in 2.0% of patients. Reduction of loop diuretic dose within the first 6 months of starting an SGLT2i occurred in 8.0% of patients. From baseline to 12 months after starting SGLT2i therapy, 14.0% of patients had loop diuretic dose reduction. Conclusions: Most of our patients with HF did not have change in loop diuretic dose after initiation of an SGLT2i. In patients who did have loop diuretic dose reduction, most occurred within 6 months after starting SGLT2i therapy rather than empirically at time of initiation.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Estudos Retrospectivos , Insuficiência Cardíaca/tratamento farmacológico , Glucose/uso terapêutico , Sódio/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
In the eastern United States, land-use and climate change have likely contributed to declines in the abundance of Neotropical migrant birds that occupy forest interiors, but the mechanisms are not well understood. We conducted a nest-predation experiment in southern Appalachian Mountain forests (North Carolina, U.S.A.) during the 2009 and 2010 breeding seasons to determine the effects of exurban development and temperature on predator presence and the average number of days until eggs in an artificial nest were disturbed by predators. We baited artificial nests with quail (Excalfactoria chinensi) eggs and monitored them for 18 days. We used clay eggs, track plates, and motion-triggered cameras to detect and identify nest predators. The average number of days a nest was undisturbed decreased as mean temperature increased and, to a lesser extent, as the density of buildings increased. Nests on the ground were more often depredated than those in trees, likely due to increased predation by opossum (Didelphis virginiana) and other carnivores. Raccoons (Procyon lotor), opossums, corvids (Corvus brachyrhynchos and Cyanocitta cristata), chipmunks (Tamias striatus), black bears (Ursus americanus), and domestic cats (Felis catus) were the most commonly detected predators. Presence of these predators did not vary as a function of mean temperature. Domestic cats and corvids were detected more frequently in plots with high rather than low densities of buildings. Forest-interior specialists and Neotropical migrants often nest in cool, high-elevation areas with low housing density. These bird species, especially those that nest on the ground, may be most vulnerable to increased nest predation if temperature and exurban development increase at higher elevations as anticipated.
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Aves/fisiologia , Cadeia Alimentar , Atividades Humanas , Reprodução , Animais , Humanos , North Carolina , Densidade Demográfica , Estações do Ano , TemperaturaRESUMO
Many older adults experience a deterioration in cognitive function with aging, and this can have a negative impact on quality of life. Late-life depression has been linked to mild cognitive impairment and dementia, and treating depression with an agent that has procognitive effects could be beneficial. Vortioxetine is a novel antidepressant with a multimodal mechanism of action that works primarily via serotonin transporter inhibition, 5-HT1A receptor agonism and 5-HT3 receptor antagonism. A recent systematic review demonstrated procognitive effects of vortioxetine when indirectly compared with selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in adults aged 18-65 years with major depressive disorder. While this systematic review demonstrated promising procognitive effects from vortioxetine, the included studies did not enroll older adults, who are at the highest risk of cognitive impairment. Therefore, our systematic review sought to investigate the effects of vortioxetine on cognitive functioning in patients over the age of 65 years. Three studies met the prespecified search criteria and were evaluated. Overall, these preliminary data suggest that vortioxetine has promising effects in improving cognition in older adults with depressive symptoms and may have a place in therapy in older adults with depression and/or cognitive impairment, including Alzheimer's disease. Additional long-term studies that include more diverse populations with comorbidities and direct comparisons with other antidepressants are needed to fully understand the potential cognitive benefits in older adults.
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Objective: To describe two pharmacist-led initiatives aimed to reduce potentially inappropriate medication (PIM) use in community-dwelling patients with dementia or cognitive impairment. Design: Retrospective, descriptive analysis of two clinical initiatives. Setting: Academic geriatric primary care clinics. Participants: Patients were included if they received a Memory Clinic pharmacist review May 1, 2017, to December 31, 2019, or a Living with Dementia (LWD) program pharmacist review November 15, 2018 to December 31, 2019 with provider follow-up within 6 months. Interventions: Both initiatives involved medication review by a clinical pharmacist to identify and make recommendations regarding medications that may contribute to cognitive impairment. The Memory Clinic served patients with concerns of cognitive impairment; whereas, the LWD program enrolled patients with an established diagnosis of dementia. Main Outcome Measure: Number of PIMs that could negatively impact cognition within each cohort. Additionally, 6-month implementation rates were analyzed for actionable pharmacist recommendations. RESULTS: Memory Clinic patients (n = 110) were taking an average of 2.4 PIMs; whereas, LWD patients (n = 40) were taking an average of 1.5 PIMs. Six-month implementation rates for all actionable pharmacist recommendations were 61.0% for the Memory Clinic and 42.4% for the LWD program. Specifically evaluating deprescribing recommendations, the 6-month PIM discontinuation rate was 63.6% for the Memory Clinic group and 60.0% for the LWD group. Conclusion: Pharmacists routinely identified PIMs during medication reviews, which led to successful recommendation implementation throughout multiple stages of cognitive decline. Both programs will continue to be adapted to ensure maximal impact.
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Disfunção Cognitiva , Farmacêuticos , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Humanos , Lista de Medicamentos Potencialmente Inapropriados , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the impact of a pharmacist-led transitional care intervention targeting high-risk older people after an emergency department (ED) visit.
DESIGN: Retrospective cohort study of older people with ED visits prior to and during a pharmacist-led intervention.
SETTING: Patients receiving primary care from the University of Colorado Health Seniors Clinic.
PARTICIPANTS: The intervention cohort comprised 170 patients with an ED visit between August 18, 2018, and February 19, 2019, and the historical cohort included 166 patients with an ED visit between August 18, 2017, and February 19, 2018. All included patients either had a historical diagnosis of heart failure or chronic obstructive pulmonary disease, or they had an additional ED visit in the previous six months.
INTERVENTIONS: The pilot intervention involved postED discharge telephonic outreach and assessment by a clinical pharmacist, with triaging to other staff if necessary.
MAIN OUTCOME MEASURE: The primary outcome was the proportion of patients with at least one repeat ED visit, hospitalization, or death within 30 days of ED discharge. Outcome rates were also assessed at 90 days postdischarge.
RESULTS: The primary outcome occurred in 21% of the historical cohort and 25% of the intervention cohort (adjusted P-value = 0.48). The incidence of the composite outcome within 90 days of ED discharge was 43% in the historical group compared with 38% in the intervention group (adjusted P-value = 0.29).
CONCLUSION: A pharmacist-led telephonic intervention pilot targeting older people did not appear to have a significant effect on the composite of repeat ED visit, hospitalization, or death within 30 or 90 days of ED discharge. A limited sample size may hinder the ability to make definitive conclusions based on these findings.
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Transferência de Pacientes , Farmacêuticos , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Humanos , Alta do Paciente , Readmissão do Paciente , Projetos Piloto , Estudos RetrospectivosRESUMO
Biodiversity-based cultural ecosystem services (CES), such as birdwatching, are strongly influenced by biotic community dynamics. However, CES models are largely static, relying on single estimates of species richness or land-use/land-cover proxies, and may be inadequate for landscape management of CES supply. Using bird survey data from the Appalachian Mountains (USA), we developed spatial-temporal models of five CES indicators (total bird species richness, and richness of migratory, infrequent, synanthrope, and resident species), reflecting variation in birdwatcher preferences. We analyzed seasonal shifts in birdwatching supply and how those shifts impacted public access to projected birdwatching hotspots. Landscape patterns of CES supply differed substantially among indicators, leading to opposing conclusions about locations of highest birdwatching supply. Total species richness hotspots seldom overlapped with hotspots of migratory or infrequent species. Public access to CES hotspots varied seasonally. Our study suggests that simple, static biodiversity metrics may overlook spatial dynamics important to CES users.
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Aves , Ecossistema , Animais , Biodiversidade , Dinâmica Populacional , Estações do AnoRESUMO
OBJECTIVE: To review clinical studies evaluating melatonin doses and their effects on sleep in adults 65 years of age and older. DATA SOURCES: The MEDLINE databases were searched (1946 to October 10, 2018) using the following Medical Subject Heading terms: melatonin and: sleep initiation and maintenance disorders, dyssomnia, sleep wake disorders, insomnia, sleep disorders intrinsic, and sleep disorders circadian rhythm. Sources were limited to English and human data. STUDY SELECTION/DATA EXTRACTION: An initial search resulted in 144 publications, with 25 included in this review. Studies were selected for full review based on design, mean age of participants, use of exogenous melatonin, and reports on any sleep-related outcome. DATA SYNTHESIS: Because of the side effect profiles of most prescription and nonprescription sleep aids, safe and effective alternative therapies are necessary. Based on the current literature, no dose-related response to sleep improvement has been identified for melatonin in older adults. Variations in melatonin formulation and dosages, as well as available tools to measure sleep outcomes, make it challenging to compare studies. CONCLUSIONS: This review evaluated a variety of melatonin doses, 0.5 mg to 10 mg, and their effects on sleep in older adults. The results varied, with some studies finding no difference in sleep outcomes when compared with placebo, while other studies found statistically significant improvements in sleep outcomes. Doses of melatonin between 1 mg and 6 mg appear to be effective for improving sleep in older adults; however, further studies are needed to find the optimal minimum effective dose.
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Melatonina/administração & dosagem , Transtornos do Sono-Vigília , Ritmo Circadiano , Humanos , SonoRESUMO
BACKGROUND: We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. METHODS: This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 (n = 95) or insulin degludec (n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1-12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. RESULTS: Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19-60 interquartile range (IQR)] units at baseline to 34.5 (19-70 IQR) units after follow up (p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different (p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 (p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. CONCLUSIONS: Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different.
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BACKGROUND: A case of 5-alpha-dihydrotestosterone (DHT) elevation associated with phentermine initiation is reported, and possible mechanisms are discussed. There are no published reports of this association in the literature. METHODS: Clinical and laboratory information is described. RESULTS: A 72-year-old male with metastatic prostate cancer taking dutasteride to lower his DHT levels initiated phentermine 15 mg daily for weight loss. His DHT level drawn within 1 week prior to starting phentermine was 9.9 pg/ml. When reporting for follow up 2 weeks later, his DHT level had increased to 114 pg/ml. The DHT level was checked again 2 weeks after that visit, and had increased to 174 pg/ml. At that time, phentermine was discontinued, and 1 week later, the DHT level had decreased to 20.1 pg/ml. Over the next 4 months, the patient's DHT levels were maintained at less than 20 pg/ml. Phentermine 15 mg daily was then reinitiated while his DHT level was 7.5 pg/ml. Two weeks after resuming phentermine, his DHT level had again increased to 196 pg/ml. The patient's phentermine was then discontinued, and around 1 week later, his DHT level had fallen to 5.1 pg/ml. CONCLUSION: A 72-year-old male with metastatic prostate cancer experienced profound increases in DHT upon initiation of phentermine despite continuation of his baseline dutasteride therapy. The etiology of these increases is still unclear.
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BACKGROUND: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients. METHODS AND RESULTS: We characterized patients in PARADIGM-HF by whether they reported hypotension during study run-in periods (enalapril, followed by sacubitril/valsartan) and after randomization and assessed whether hypotension modified the efficacy of sacubitril/valsartan. Of the 10 513 patients entering the enalapril run-in, 136 (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228 (2.4%) patients experienced hypotension and 51% were unable to successfully complete the run-in. After randomization, 388 (9.2%) participants had 501 hypotensive events with enalapril, and 588 (14.0%) participants had 803 hypotensive events with sacubitril/valsartan (P<0.001). There was no difference between randomized treatment groups in the number of participants who discontinued therapy because of hypotension. Individuals with a hypotensive event in either group were older, had lower blood pressure at randomization, and were more likely to have an implantable cardioverter defibrillator. Participants with hypotensive events during run-in who were ultimately randomized derived similar efficacy from sacubitril/valsartan compared with enalapril as those without hypotensive events (P interaction>0.90). CONCLUSIONS: Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived similar benefit from sacubitril/valsartan compared with enalapril as those who did not experience hypotension.