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Despite published algorithms for approaching the work-up of erythrocytosis, a significant proportion of patients are left with uncertainty as to its aetiology and prognosis. The term 'idiopathic erythrocytosis' (IE) is applied when known primary and secondary aetiologies have been ruled out. However, the assignment of secondary aetiologies is not always straightforward or evidence based, which can lead to misdiagnosis and heterogeneity in cohort studies. Furthermore, new studies have identified germline or somatic mutations that may affect prognosis. Epidemiological and cohort data are inconsistent as to whether IE increases the risk for complications such as arterial and venous thromboembolism, clonal transformation or comorbid conditions. Randomized trials assessing the role of phlebotomy for long-term management of IE have not been performed, so treatment remains a vexing problem for clinicians. Standardization of terminology and testing strategies, including comprehensive genetic screening in clinical research, are key to refining our understanding of IE.
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Policitemia , Humanos , Policitemia/genética , Estudos de Coortes , Testes Genéticos , PrognósticoRESUMO
BACKGROUND: Clonal cytopenia of undetermined significance (CCUS) is defined as somatic mutations of myeloid malignancy-associated genes in the blood or bone marrow with one or more persistent unexplained cytopenias that do not meet diagnostic criteria for a defined myeloid neoplasm. CCUS with isolated thrombocytopenia (CCUS-IT) is rare. METHODS: This is a retrospective case series of patients with prolonged isolated thrombocytopenia, a pathogenic mutation on a myeloid molecular panel, and a bone marrow biopsy with morphologic atypia below the WHO-defined diagnostic threshold for dysplasia. RESULTS: Five male patients were identified with a median age at CCUS-IT diagnosis of 61 years (56-74). Median duration of thrombocytopenia prior to CCUS-IT diagnosis was 4 years (3-12), and median platelet count at CCUS-IT diagnosis was 41 × 103 /µL (26-80). All patients had megakaryocytic hyperplasia and megakaryocytes with hyperchromasia and high nuclear-cytoplasmic ratio. Pathogenic SRSF2 mutations were identified in all 5 patients with median variant allele frequency of 36% (28%-50%). Three patients were treated with IVIg and/or steroids with no response; one of three responded to thrombopoietin receptor agonists. Three patients progressed to MDS and one to AML. DISCUSSION: We describe the clinicopathological features of CCUS-IT which can mimic immune thrombocytopenia.
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Citopenia , Transtornos Mieloproliferativos , Trombocitopenia , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Hematopoese/genética , Transtornos Mieloproliferativos/diagnóstico , Mutação , Trombocitopenia/etiologia , Trombocitopenia/genéticaRESUMO
People who use drugs (PWUD) are the most directly affected by the overdose epidemic. However, they are not often targets of overdose education and naloxone distribution (OEND) programs. Instead, these programs target friends or family members of people prescribed opioids or general community members. This study aimed to understand the perspectives of PWUD and community naloxone distributors on OEND program design. We used a community-based participatory research model to elucidate participant perspectives on what OEND programs should look like in the context of each individual's specific risk environment. We conducted semi-structured in-depth interviews with PWUD and naloxone distributors (n = 30) in New Brunswick and Newark, New Jersey between February and November of 2022. We analyzed interviews using thematic analysis and identified the following themes: increasing naloxone knowledge, peer-based naloxone access, increasing PWUD-informed OEND program design, and desired broader OEND program scope. All Participants knew what naloxone was and emphasized that naloxone needed to be ubiquitous in the community. Participants prioritized peer-based distribution, integrating distribution into community organizations, and addressing psychosocial issues related to naloxone administration and drug use. In summary, PWUD and community naloxone distributors emphasized peer-led community naloxone distribution that prioritized novel ways for PWUD to access naloxone. OEND program design should prioritize PWUD's perspectives and direct community naloxone distribution.
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INTRODUCTION: Cognitive activity and awareness during cardiac arrest (CA) are reported but ill understood. This first of a kind study examined consciousness and its underlying electrocortical biomarkers during cardiopulmonary resuscitation (CPR). METHODS: In a prospective 25-site in-hospital study, we incorporated a) independent audiovisual testing of awareness, including explicit and implicit learning using a computer and headphones, with b) continuous real-time electroencephalography(EEG) and cerebral oxygenation(rSO2) monitoring into CPR during in-hospital CA (IHCA). Survivors underwent interviews to examine for recall of awareness and cognitive experiences. A complementary cross-sectional community CA study provided added insights regarding survivors' experiences. RESULTS: Of 567 IHCA, 53(9.3%) survived, 28 of these (52.8%) completed interviews, and 11(39.3%) reported CA memories/perceptions suggestive of consciousness. Four categories of experiences emerged: 1) emergence from coma during CPR (CPR-induced consciousness [CPRIC]) 2/28(7.1%), or 2) in the post-resuscitation period 2/28(7.1%), 3) dream-like experiences 3/28(10.7%), 4) transcendent recalled experience of death (RED) 6/28(21.4%). In the cross-sectional arm, 126 community CA survivors' experiences reinforced these categories and identified another: delusions (misattribution of medical events). Low survival limited the ability to examine for implicit learning. Nobody identified the visual image, 1/28(3.5%) identified the auditory stimulus. Despite marked cerebral ischemia (Mean rSO2 = 43%) normal EEG activity (delta, theta and alpha) consistent with consciousness emerged as long as 35-60 minutes into CPR. CONCLUSIONS: Consciousness. awareness and cognitive processes may occur during CA. The emergence of normal EEG may reflect a resumption of a network-level of cognitive activity, and a biomarker of consciousness, lucidity and RED (authentic "near-death" experiences).
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Reanimação Cardiopulmonar , Parada Cardíaca , Parada Cardíaca Extra-Hospitalar , Humanos , Estado de Consciência , Reanimação Cardiopulmonar/métodos , Estudos Prospectivos , Estudos Transversais , Morte , BiomarcadoresRESUMO
Abstract: Imported, minimally processed food products have been historically associated with several hepatitis A outbreaks in Australia. Here, we report the first known hepatitis A outbreak in Australia linked to consumption of imported fresh Medjool dates. Between June and September 2021, six genetically identical hepatitis A cases were notified in New South Wales and the Australian Capital Territory. All cases reported date consumption during their exposure period. The implicated dates were positive for hepatitis A virus (HAV) by reverse transcription polymerase chain reaction. Rapid detection of this outbreak and the swift implementation of control measures was facilitated by two key factors. Firstly, Australian international border closures implemented in response to the COVID-19 pandemic meant that a common locally-acquired, as opposed to travel-acquired, source for cases was strongly suspected. Secondly, prompt awareness of a hepatitis A outbreak in the United Kingdom (which was found to be associated with date consumption) allowed for early hypothesis generation and investigation. This paper details the epidemiological and microbiological factors involved in this outbreak investigation and the actions taken to mitigate public health risk.
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COVID-19 , Hepatite A , Humanos , Austrália/epidemiologia , Hepatite A/epidemiologia , Pandemias , COVID-19/epidemiologia , Surtos de DoençasRESUMO
Although exercise training is an important recommendation for the management of type 1 diabetes (T1D), most of the available research studies predominantly focus on male subjects. Given the importance of sex as a biological variable, additional studies are required to improve the knowledge gap regarding sex differences in T1D research. Therefore, the purpose of this study was to examine the role of exercise training in mediating changes in glucose homeostasis and skeletal muscle metabolism in T1D female mice. Female mice were injected with streptozotocin (STZ) to induce T1D. Two weeks after STZ injection, control (CON) and STZ mice were exercise trained on a treadmill for 4 weeks. Aerobic exercise training failed to improve glucose tolerance, prevent the decrease in body weight and adipose tissue mass, or attenuate muscle atrophy in T1D female mice. However, insulin sensitivity was improved in T1D female mice after exercise training. Aerobic exercise training maintained skeletal muscle triglyceride content but did not prevent depletion of skeletal muscle or liver glycogen in T1D mice. Gene expression analysis suggested that T1D resulted in decreased glucose transport, decreased ketone body oxidation, and increased fatty acid metabolism in the skeletal muscle, which was not altered by exercise training. These data demonstrate that 4 weeks of aerobic exercise training of a moderate intensity is insufficient to counteract the negative effects of T1D in female mice, but does lead to an improvement in insulin sensitivity.
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Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased utilization of muscle triglycerides. However, whether these changes in lipid metabolism contribute directly to endurance exercise performance is unclear. Therefore, the objective of this study was to investigate the contribution of exercise substrate metabolism to sex differences in endurance exercise capacity (EEC) in mice. Male and female C57BL/6-NCrl mice were subjected to an EEC test until exhaustion on a motorized treadmill. The treadmill was set at a 10% incline, and the speed gradually increased from 10.2 m/min to 22.2 m/min at fixed intervals for up to 2.5 h. Tissues and blood were harvested in mice immediately following the EEC. A cohort of sedentary, non-exercised male and female mice were used as controls. Females outperformed males by ~25% on the EEC. Serum levels of both fatty acids and ketone bodies were ~50% higher in females at the end of the EEC. In sedentary female mice, skeletal muscle triglyceride content was significantly greater compared to sedentary males. Gene expression analysis demonstrated that genes involved in skeletal muscle fatty acid oxidation were significantly higher in females with no changes in genes associated with glucose uptake or ketone body oxidation. The findings suggest that female mice have a higher endurance exercise capacity and a greater ability to mobilize and utilize fatty acids for energy.
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Metabolismo dos Lipídeos , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/métodos , Corrida , Animais , Feminino , Corpos Cetônicos/sangue , Corpos Cetônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/fisiologia , Caracteres Sexuais , Triglicerídeos/sangue , Triglicerídeos/metabolismoAssuntos
Aditivos Alimentares/intoxicação , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Nitrito de Sódio/intoxicação , Adulto , Ingestão de Alimentos/fisiologia , Serviço Hospitalar de Emergência , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Aditivos Alimentares/efeitos adversos , Humanos , Metemoglobinemia/sangue , Metemoglobinemia/diagnóstico , Azul de Metileno/administração & dosagem , Azul de Metileno/uso terapêutico , Nitrito de Sódio/efeitos adversos , Resultado do TratamentoRESUMO
The promotion of ketone body (KB) metabolism via ketosis has been suggested as a strategy to increase exercise performance. However, studies in humans and animals have yielded inconsistent results. The purpose of the current study was to examine the effects of ketosis, achieved via fasting or a short-term ketogenic diet (KD), on endurance exercise performance in female mice. After 8 h of fasting, serum KB significantly increased and serum glucose significantly decreased in fasted compared to fed mice. When subjected to an endurance exercise capacity (EEC) test on a motorized treadmill, both fed and fasted mice showed similar EEC performance. A 5-week KD (90% calories from fat) significantly increased serum KB but did not increase EEC times compared to chow-fed mice. KD mice gained significantly more weight than chow-fed mice and had greater adipose tissue mass. Biochemical tissue analysis showed that KD led to significant increases in triglyceride content in the heart and liver and significant decreases in glycogen content in the muscle and liver. Furthermore, KD downregulated genes involved in glucose and KB oxidation and upregulated genes involved in lipid metabolism in the heart. These findings suggest that a short-term KD is not an effective strategy to enhance exercise performance and may lead to increased adiposity, abnormal endogenous tissue storage, and cardiometabolic remodeling.
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Facilitating coexistence between people and wildlife is a major conservation challenge in East Africa. Some conservation models aim to balance the needs of people and wildlife, but the effectiveness of these models is rarely assessed. Using a case-study approach, we assessed the ecological performance of a pastoral area in northern Tanzania (Manyara Ranch) and established a long-term wildlife population monitoring program (carried out intermittently from 2003 to 2008 and regularly from 2011 to 2019) embedded in a distance sampling framework. By comparing density estimates of the road transect-based long-term monitoring to estimates derived from systematically distributed transects, we found that the bias associated with nonrandom placement of transects was nonsignificant. Overall, cattle and sheep and goat reached the greatest densities and several wildlife species occurred at densities similar (zebra, wildebeest, waterbuck, Kirk's dik-dik) or possibly even greater (giraffe, eland, lesser kudu, Grant's gazelle, Thomson's gazelle) than in adjacent national parks in the same ecosystem. Generalized linear mixed models suggested that most wildlife species (8 out of 14) reached greatest densities during the dry season, that wildlife population densities either remained constant or increased over the 17-year period, and that herbivorous livestock species remained constant, while domestic dog population decreased over time. Cross-species correlations did not provide evidence for interference competition between grazing or mixed livestock species and wildlife species but indicate possible negative relationships between domestic dog and warthog populations. Overall, wildlife and livestock populations in Manyara Ranch appear to coexist over the 17-year span. Most likely, this is facilitated by existing connectivity to adjacent protected areas, effective anti-poaching efforts, spatio-temporal grazing restrictions, favorable environmental conditions of the ranch, and spatial heterogeneity of surface water and habitats. This long-term case study illustrates the potential of rangelands to simultaneously support wildlife conservation and human livelihood goals if livestock grazing is restricted in space, time, and numbers.
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OBJECTIVE: Cerebral oximetry is a non-invasive system that uses near infrared spectroscopy to measure regional cerebral oxygenation (rSO2) in the frontal lobe of the brain. Post-cardiac arrest rSO2 may be associated with survival and neurological outcomes in out-of-hospital cardiac arrest patients; however, no studies have examined relationships between rSO2 and neurological outcomes following in-hospital cardiac arrest (IHCA). We tested the hypothesis that rSO2 following IHCA is associated with survival and favorable neurological outcomes. DESIGN: Prospective study from nine acute care hospital in the United States and United Kingdom. PATIENTS: Convenience sample of IHCA patients admitted to the intensive care unit with post-cardiac arrest syndrome. INTERVENTIONS: Cerebral oximetry monitoring (Equanox 7600, Nonin Medical, MN, USA) during the first 48â¯h after IHCA. MEASUREMENTS AND MAIN RESULTS: Subject's rSO2 was calculated as the mean of collected data at different time intervals: hourly between 1-6â¯h, 6-12â¯h, 12-18â¯h, 18-24â¯h and 24-48â¯h. Demographic data pertaining to possible confounding variables for rSO2 and primary outcome were collected. The primary outcome was survival with favorable neurological outcomes (cerebral performance scale [CPC] 1-2) vs severe neurological injury or death (CPC 3-5) at hospital discharge. Univariate and multivariate statistical analyses were performed to correlate cerebral oximetry values and other variables with the primary outcome. Among 87 studied patients, 26 (29.9%) achieved CPC 1-2. A significant difference in mean rSO2 was observed during hours 1-2 after IHCA in CPC 1-2 vs CPC 3-5 (73.08 vs. 66.59, pâ¯=â¯0.031) but not at other time intervals. There were no differences in age, Charlson comorbidity index, APACHE II scores, CPR duration, mean arterial pressure, PaO2, PaCO2, and hemoglobin levels between two groups. CONCLUSIONS: There may be a significant physiological difference in rSO2 in the first two hours after ROSC in IHCA patients who achieve favorable neurological outcomes, however, this difference may not be clinically significant.
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Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Circulação Cerebrovascular , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Oximetria , Estudos Prospectivos , Reino Unido/epidemiologiaRESUMO
Anthropogenic noise associated with shipping has emerged as a major disruptor of aquatic animal behavior worldwide. The Arctic marine realm has historically experienced little noise-generating human activity; however, the continual loss of sea ice has facilitated a dramatic increase in shipping activity. Here, we use a combination of acoustic telemetry and modeling of ship noise to examine the temporospatial habitat use of key Arctic forage fish, Arctic cod (Boreogadus saida) in the presence and absence of vessels in Resolute Bay, Nunavut, Canada. The presence and movement of vessels induced a horizontal shift in the home ranges of Arctic cod with low core overlap when compared to periods without vessel activity. Home range displacement occurred near the vessel. Individuals also altered their swimming behaviors in response to vessel presence with searching decreasing and travelling increasing in proportion. Results indicate that Arctic cod perceive vessel noise and presence as a threat and react by moving away and decreasing exploratory activities. These changes in fish behavior also coincide with the critical open water feeding period suggesting an interruption in exploitation of important and seasonally abundant food resources, and carry broader implications for dependent seabirds and marine mammals, and indirectly for all Arctic indigenous peoples' subsistence and long-term cultural traditions. Our study implies that strategic management is required for aquatic acoustic disturbance as an environmental stressor in the Arctic marine ecosystem, and highlights ecologically and socially important impacts that require timely conservation action.
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Ecossistema , Navios , Animais , Regiões Árticas , Canadá , Peixes , HumanosRESUMO
While most bacterial and archaeal taxa living in surface soils remain undescribed, this problem is exacerbated in deeper soils, owing to the unique oligotrophic conditions found in the subsurface. Additionally, previous studies of soil microbiomes have focused almost exclusively on surface soils, even though the microbes living in deeper soils also play critical roles in a wide range of biogeochemical processes. We examined soils collected from 20 distinct profiles across the United States to characterize the bacterial and archaeal communities that live in subsurface soils and to determine whether there are consistent changes in soil microbial communities with depth across a wide range of soil and environmental conditions. We found that bacterial and archaeal diversity generally decreased with depth, as did the degree of similarity of microbial communities to those found in surface horizons. We observed five phyla that consistently increased in relative abundance with depth across our soil profiles: Chloroflexi, Nitrospirae, Euryarchaeota, and candidate phyla GAL15 and Dormibacteraeota (formerly AD3). Leveraging the unusually high abundance of Dormibacteraeota at depth, we assembled genomes representative of this candidate phylum and identified traits that are likely to be beneficial in low-nutrient environments, including the synthesis and storage of carbohydrates, the potential to use carbon monoxide (CO) as a supplemental energy source, and the ability to form spores. Together these attributes likely allow members of the candidate phylum Dormibacteraeota to flourish in deeper soils and provide insight into the survival and growth strategies employed by the microbes that thrive in oligotrophic soil environments.IMPORTANCE Soil profiles are rarely homogeneous. Resource availability and microbial abundances typically decrease with soil depth, but microbes found in deeper horizons are still important components of terrestrial ecosystems. By studying 20 soil profiles across the United States, we documented consistent changes in soil bacterial and archaeal communities with depth. Deeper soils harbored communities distinct from those of the more commonly studied surface horizons. Most notably, we found that the candidate phylum Dormibacteraeota (formerly AD3) was often dominant in subsurface soils, and we used genomes from uncultivated members of this group to identify why these taxa are able to thrive in such resource-limited environments. Simply digging deeper into soil can reveal a surprising number of novel microbes with unique adaptations to oligotrophic subsurface conditions.
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Archaea/isolamento & purificação , Bactérias/isolamento & purificação , Microbiologia do Solo , Archaea/classificação , Archaea/crescimento & desenvolvimento , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , MetagenômicaRESUMO
The auditory frequency weighted daily sound exposure level (SEL) is used in many jurisdictions to assess possible injury to the hearing of marine life. Therefore, using daily SEL to describe soundscapes would provide baseline information about the environment using the same tools used to measure injury. Here, the daily SEL from 12 recordings with durations of 18-97 days are analyzed to: (1) identify natural soundscapes versus environments affected by human activity, (2) demonstrate how SEL accumulates from different types of sources, (3) show the effects of recorder duty cycling on daily SEL, (4) make recommendations on collecting data for daily SEL analysis, and (5) discuss the use of the daily SEL as an indicator of cumulative effects. The autocorrelation of the one-minute sound exposure is used to help identify soundscapes not affected by human activity. Human sound sources reduce the autocorrelation and add low-frequency energy to the soundscapes. To measure the daily SEL for all marine mammal auditory frequency weighting groups, data should be sampled at 64 kHz or higher, for at least 1 min out of every 30 min. The daily autocorrelation of the one-minute SEL provides a confidence interval for the daily SEL computed with duty-cycled data.
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Immune thrombocytopenia (ITP) is an autoimmune disorder with a complex immunopathology and pathogenesis characterized by thrombocytopenia and bleeding manifestations. The disorder is separated into primary (idiopathic) ITP and secondary ITP, when associated with other immune or lymphoproliferative disorders and certain chronic infections. Helicobacter pylori (H. pylori) is a recognized bacterial cause of ITP. In regions with high prevalence of infection, bacterial eradication has resulted in improvement in platelet count. However, the prevalence of H. pylori infection and response to antimicrobial therapy in North American ITP patients is reportedly low. We evaluated the prevalence of H. pylori infection in ITP patients diagnosed and treated at a large urban medical center. Eighty-two patients were screened for H. pylori, by stool antigen (n = 54), H. pylori breath test (n = 11), and H. pylori antibodies (n = 16), of which 15 (18.3%) were white non-Hispanic (WNH), 55 (67%) Hispanic (H), 8 (9.8%) Asian (A), and 4 (4.9%) African-American (AA). Of the screened patients, 36/82 (43.9%) tested positive for H. pylori. The prevalence of H. pylori infection within the represented ethnic groups was 2/15 (13%) WNH, 29/55 (52.7%) H, 3/8 (37.5%) A, and 2/4 (50%) AA. There was a significant difference in prevalence of infection comparing WNH and H patients (p = 0.007). There were 36 treated patients, with H. pylori eradication documented in 26 patients. Fifteen of the 26 patients were evaluable for response with 8 of 15 (53%) having clinical responses, 6 complete responses, and 2 partial responses. Our study demonstrates an increased prevalence of H. pylori infection in the Hispanic ITP population with a reasonable platelet response among patients with H. pylori eradication.
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Infecções por Helicobacter/epidemiologia , Helicobacter pylori/patogenicidade , Trombocitopenia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Etnicidade , Feminino , Hospitais Urbanos , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Raciais , Estudos Retrospectivos , Trombocitopenia/patologia , Adulto JovemRESUMO
INTRODUCTION: Myelofibrosis (MF) is one of the classic myeloproliferative neoplasms and can occur de novo or following transformation from polycythemia vera (PPV MF) or essential thrombocythemia (PET MF). It can be associated with constitutional symptoms and splenomegaly, both of which can negatively impact quality of life. The only curative option for MF is allogeneic stem cell transplantation. Studies have shown that JAK2 inhibitors such as ruxolitinib are effective in reducing both splenomegaly and symptom burden. Although there is no approved treatment for patients who progress on ruxolitinib, anecdotal evidence suggests patients may respond to a re-challenge of ruxolitinib after drug cessation. PATIENTS AND METHODS: We conducted a multi-institutional, retrospective case series to study patients who were re-challenged with ruxolitinib after inadequate response to or loss of response with an initial treatment course. Thirteen patients were identified. Six patients had primary MF, 3 patients had PPV MF, and 4 patients had PET MF. Ten patients were JAK2-positive, 2 were CALR-positive, and 1 patient had neither mutation. Nine patients received 1 ruxolitinib re-challenge, and 4 received 2 re-challenges. Response was defined as improvement in constitutional symptoms and/or reduction in spleen size. RESULTS: During the primary treatment course with ruxolitinib, there was improvement in constitutional symptoms and reduction in spleen size in 92% and 85% of patients, respectively. Following cessation of ruxolitinib, all patients received a first re-challenge course with improvement in symptoms and splenomegaly in 92% and 69%, respectively. Of the 4 patients who received a second re-challenge course of ruxolitinib, all had improvements in spleen size and constitutional symptoms. Six patients have continued on a first or second ruxolitinib re-challenge course with good response. CONCLUSION: Our study demonstrates that re-exposure to ruxolitinib following a period of treatment cessation in patients with MF can lead to durable responses with regards to both splenomegaly and symptom burden.
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Mielofibrose Primária/complicações , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Qualidade de Vida , Índice de Gravidade de Doença , Esplenomegalia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Prognóstico , Pirimidinas , Retratamento , Estudos Retrospectivos , Esplenomegalia/etiologia , Suspensão de TratamentoRESUMO
Pegylated interferon α-2a (Peg-IFN) has been shown to induce hematologic and molecular responses in patients with the Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET). We describe a series of patients with long-standing MPNs among whom Peg-IFN was initiated when they developed anemia and increased bone marrow reticulin fibrosis suggestive of early transformation to post-ET (PET) or post-PV (PPV) myelofibrosis (MF). Six patients were treated with Peg-IFN for a mean duration of 33.8 months (range 2-63 months). Five patients had long-standing ET (three were calreticulin (CALR)-positive, one janus kinase 2 (JAK2)-positive, and one JAK2-negative and CALR-negative), and one had long-standing JAK2-positive PV prior to starting Peg-IFN. This is the first study to report that, concurrent with the improvement in anemia, serial laboratory studies demonstrate an increase in serum LDH and left-shifted myeloid cells in the peripheral circulation over approximately 6 months, followed by a gradual normalization of these findings. Splenomegaly also increased and then resolved among responding patients. Serial bone marrow biopsies were available, which showed little change except for improvement in the grade of reticulin fibrosis in two patients. Among patients with early transformation to PET or PPV MF, our data support the efficacy of Peg-IFN in improving hemoglobin levels and reducing splenomegaly. These peripheral blood findings should not, therefore, be considered evidence of treatment failure within the first year of Peg-IFN therapy.
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Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anemia/tratamento farmacológico , Anemia/etiologia , Biomarcadores , Medula Óssea/patologia , Exame de Medula Óssea , Progressão da Doença , Avaliação de Medicamentos , Feminino , Hemoglobinas/análise , Humanos , Interferon alfa-2 , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Policitemia Vera/complicações , Policitemia Vera/patologia , Mielofibrose Primária/sangue , Mielofibrose Primária/etiologia , Proteínas Recombinantes/uso terapêutico , Reticulina/ultraestrutura , Método Simples-Cego , Esplenomegalia/etiologia , Esplenomegalia/prevenção & controle , Trombocitemia Essencial/complicações , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologiaRESUMO
BACKGROUND AND OBJECTIVES: The patient-centered medical home (PCMH) is a practice model that is intended to improve the quality of care by making it safer, more comprehensive, integrated, and personal. However, most family medicine residency programs are not fully prepared to train residents on this idealized model. The Colorado Family Medicine Residency PCMH Project's overall objective is to transform 10 residency practices into PCMHs through practice improvement and curriculum redesign. This paper focuses on the programs' implementation of key PCMH components into the residency curricula and the impact on resident self-perceived competence in and use of PCMH components. METHODS: Mixed-method evaluation assessed PCMH curricular characteristics, routine use of PCMH components in patient care, and perceived resident competence after implementation of quality improvement coaching and PCMH curriculum tools. Baseline and follow-up PCMH semi-structured curriculum interviews assessed elements included in the residency programs' curricula. The PCMH Clinician Assessment (PCMH-CA) Survey assessed routine use of PCMH components in patient care. The PCMH Competency Self-Assessment Survey assessed residents' perceived competency in applying PCMH elements in patient care. RESULTS: Qualitative data results demonstrated active efforts by the residency programs to implement key PCMH components. Survey results showed significant improvement from baseline to follow-up (12--36 months). CONCLUSIONS: Implementation of the key components of PCMH into practice improvement efforts and residency curricula improved residents' routine use of PCMH in patient care and their perceived PCMH competence.
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Currículo , Medicina de Família e Comunidade/educação , Internato e Residência , Assistência Centrada no Paciente , Competência Clínica , Colorado , Medicina de Família e Comunidade/normas , Humanos , Entrevistas como Assunto , Assistência Centrada no Paciente/organização & administração , Assistência Centrada no Paciente/estatística & dados numéricos , Estudos Prospectivos , Melhoria de Qualidade , Autoeficácia , EnsinoRESUMO
BACKGROUND AND OBJECTIVES: Residency programs face inevitable challenges as they redesign their practices for higher quality care and resident training. Identifying and addressing early barriers can help align priorities and thereby augment the capacity to change. METHODS: Evaluation of the Colorado Family Medicine Residency PCMH Project included iterative qualitative analysis of field notes, interviews, and documents to identify early barriers to change and strategies to overcome them. RESULTS: Nine common but not universal barriers were identified: (1) a practice's history reflected some negative past experiences with quality improvement or routines incompatible with transformative change, (2) leadership gaps were evident in unprepared practice leaders or hierarchical leadership, (3) resistance and skepticism about change were expressed through cynicism aimed at change or ability to change, (4) unproductive team processes were reflected in patterns of canceled meetings, absentee leaders, or lack of accountability, (5) knowledge gaps about the Patient-centered Medical Home (PCMH) were apparent from incomplete dissemination about the project or planned changes, (6) EHR implementation distracted focus or stalled improvement activity, (7) sponsoring organizations' constraints emerged from staffing rules and differing priorities, (8) insufficient staff participation resulted from traditional role expectations and structures, and (9) communication was hampered by ineffective methods and part-time faculty and residents. Early barriers responded to varying degrees to specific interventions by practice coaches. CONCLUSIONS: Some barriers that interfere with practices getting started with cultural and structural transformation can be addressed with persistent attention and reflection from on-site coaches and by realigning the talents, leaders, and priorities already in these residency programs.