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BACKGROUND: Open-source automated insulin delivery (AID) systems are used by many patients with type 1 diabetes. Data are needed on the efficacy and safety of an open-source AID system. METHODS: In this multicenter, open-label, randomized, controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio to use an open-source AID system or a sensor-augmented insulin pump (control). The patients included both children (defined as 7 to 15 years of age) and adults (defined as 16 to 70 years of age). The AID system was a modified version of AndroidAPS 2.8 (with a standard OpenAPS 0.7.0 algorithm) paired with a preproduction DANA-i insulin pump and Dexcom G6 CGM, which has an Android smartphone application as the user interface. The primary outcome was the percentage of time in the target glucose range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) between days 155 and 168 (the final 2 weeks of the trial). RESULTS: A total of 97 patients (48 children and 49 adults) underwent randomization (44 to open-source AID and 53 to the control group). At 24 weeks, the mean (±SD) time in the target range increased from 61.2±12.3% to 71.2±12.1% in the AID group and decreased from 57.7±14.3% to 54.5±16.0% in the control group (adjusted difference, 14 percentage points; 95% confidence interval, 9.2 to 18.8; P<0.001), with no treatment effect according to age (P = 0.56). Patients in the AID group spent 3 hours 21 minutes more in the target range per day than those in the control group. No severe hypoglycemia or diabetic ketoacidosis occurred in either group. Two patients in the AID group withdrew from the trial owing to connectivity issues. CONCLUSIONS: In children and adults with type 1 diabetes, the use of an open-source AID system resulted in a significantly higher percentage of time in the target glucose range than the use of a sensor-augmented insulin pump at 24 weeks. (Supported by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12620000034932.).
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Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Bombas de Infusão , Insulina , Adolescente , Adulto , Idoso , Austrália , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Pessoa de Meia-Idade , Adulto JovemRESUMO
We tested the role of the sodium leak channel, NALCN, in pacemaking of dopaminergic neuron (DAN) subpopulations from adult male and female mice. In situ hybridization revealed NALCN RNA in all DANs, with lower abundance in medial ventral tegmental area (VTA) relative to substantia nigra pars compacta (SNc). Despite lower relative abundance of NALCN, we found that acute pharmacological blockade of NALCN in medial VTA DANs slowed pacemaking by 49.08%. We also examined the electrophysiological properties of projection-defined VTA DAN subpopulations identified by retrograde labeling. Inhibition of NALCN reduced pacemaking in DANs projecting to medial nucleus accumbens (NAc) and others projecting to lateral NAc by 70.74% and 31.98%, respectively, suggesting that NALCN is a primary driver of pacemaking in VTA DANs. In SNc DANs, potentiating NALCN by lowering extracellular calcium concentration speeded pacemaking in wildtype but not NALCN conditional knockout mice, demonstrating functional presence of NALCN. In contrast to VTA DANs, however, pacemaking in SNc DANs was unaffected by inhibition of NALCN. Instead, we found that inhibition of NALCN increased the gain of frequency-current plots at firing frequencies slower than spontaneous firing. Similarly, inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) conductance increased gain but had little effect on pacemaking. Interestingly, simultaneous inhibition of NALCN and HCN resulted in significant reduction in pacemaker rate. Thus, we found NALCN makes substantial contributions to driving pacemaking in VTA DAN subpopulations. In SNc DANs, NALCN is not critical for pacemaking but inhibition of NALCN makes cells more sensitive to hyperpolarizing stimuli.SIGNIFICANCE STATEMENT Pacemaking in midbrain dopaminergic neurons (DAN) relies on multiple subthreshold conductances, including a sodium leak. Whether the sodium leak channel, NALCN, contributes to pacemaking in DANs located in the VTA and the SNc has not yet been determined. Using electrophysiology and pharmacology, we show that NALCN plays a prominent role in driving pacemaking in projection-defined VTA DAN subpopulations. By contrast, pacemaking in SNc neurons does not rely on NALCN. Instead, the presence of NALCN regulates the excitability of SNc DANs by reducing the gain of the neuron's response to inhibitory stimuli. Together, these findings will inform future efforts to obtain DAN subpopulation-specific treatments for use in neuropsychiatric disorders.
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Neurônios Dopaminérgicos , Canais de Sódio , Área Tegmentar Ventral , Animais , Feminino , Masculino , Camundongos , Neurônios Dopaminérgicos/fisiologia , Canais Iônicos , Proteínas de Membrana , Mesencéfalo , Camundongos Knockout , Parte Compacta da Substância Negra , Canais de Sódio/metabolismo , Canais de Sódio/fisiologia , Substância Negra/fisiologia , Área Tegmentar Ventral/fisiologiaRESUMO
OPINION STATEMENT: The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.
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Sarcoma , Neoplasias Uterinas , Humanos , Feminino , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia , Sarcoma/terapia , Sarcoma/diagnóstico , Terapia Combinada/métodos , Estadiamento de Neoplasias , Gerenciamento Clínico , Gradação de Tumores , Resultado do Tratamento , HisterectomiaRESUMO
BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is the standard treatment for exocrine pancreatic insufficiency (EPI). However, many individuals are inadequately treated, with gaps in clinical dosing, guidelines, and tools to aid individual titration. METHODS: A systematic review identified research and guidelines on PERT dosing recommendations across conditions, systematically reviewing and synthesizing total PERT intake, meal/snack guidelines, and changes over time to provide an up-to-date look at the most common doses used in studies and guidelines. RESULTS: This review of 257 articles found wide variability in PERT dosing guidelines within and across conditions. Many patients with EPI are underdosed, with guidelines differing globally and by disease type, and clinician prescribing may also play a role. The most common dosing guidelines focus on starting doses at 40,000-50,000 units of lipase/meal with increases of up to two to three times this amount before pursuing additive therapies. Guidelines and studies typically focus only on fat digestion, and comparison by total daily dose shows underdosing is common. Most PERT studies are on safety and efficacy rather than optimal titration. CONCLUSION: The current guidelines for PERT in EPI demonstrate substantial variability in dosing recommendations, both within and across disease types. This variation highlights the need for further research to optimize PERT dosing and improve patient outcomes. Healthcare providers should consider individualizing PERT dosing based on nutritional status and response to therapy, ensuring regular follow-up with patients for dose titrations with consideration that most guidelines are framed as initial doses rather than upper limits.
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Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina , Guias de Prática Clínica como Assunto , Humanos , Insuficiência Pancreática Exócrina/tratamento farmacológico , Terapia de Reposição de Enzimas/métodos , Lipase/administração & dosagemRESUMO
BACKGROUND: Emerging research suggests that open-source automated insulin delivery (AID) may reduce diabetes burden and improve sleep quality and quality of life (QoL). However, the evidence is mostly qualitative or uses unvalidated, study-specific, single items. Validated person-reported outcome measures (PROMs) have demonstrated the benefits of other diabetes technologies. The relative lack of research investigating open-source AID using PROMs has been considered a missed opportunity. OBJECTIVE: This study aimed to examine the psychosocial outcomes of adults with type 1 diabetes using and not using open-source AID systems using a comprehensive set of validated PROMs in a real-world, multinational, cross-sectional study. METHODS: Adults with type 1 diabetes completed 8 validated measures of general emotional well-being (5-item World Health Organization Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), diabetes-specific QoL (modified DAWN Impact of Diabetes Profile), diabetes-specific positive well-being (4-item subscale of the 28-item Well-Being Questionnaire), diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire), diabetes distress (20-item Problem Areas in Diabetes scale), fear of hypoglycemia (short form of the Hypoglycemia Fear Survey II), and a measure of the impact of COVID-19 on QoL. Independent groups 2-tailed t tests and Mann-Whitney U tests compared PROM scores between adults with type 1 diabetes using and not using open-source AID. An analysis of covariance was used to adjust for potentially confounding variables, including all sociodemographic and clinical characteristics that differed by use of open-source AID. RESULTS: In total, 592 participants were eligible (attempting at least 1 questionnaire), including 451 using open-source AID (mean age 43, SD 13 years; n=189, 41.9% women) and 141 nonusers (mean age 40, SD 13 years; n=90, 63.8% women). Adults using open-source AID reported significantly better general emotional well-being and subjective sleep quality, as well as better diabetes-specific QoL, positive well-being, and treatment satisfaction. They also reported significantly less diabetes distress, fear of hypoglycemia, and perceived less impact of the COVID-19 pandemic on their QoL. All were medium-to-large effects (Cohen d=0.5-1.5). The differences between groups remained significant after adjusting for sociodemographic and clinical characteristics. CONCLUSIONS: Adults with type 1 diabetes using open-source AID report significantly better psychosocial outcomes than those not using these systems, after adjusting for sociodemographic and clinical characteristics. Using validated, quantitative measures, this real-world study corroborates the beneficial psychosocial outcomes described previously in qualitative studies or using unvalidated study-specific items.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Feminino , Masculino , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Qualidade de Vida/psicologia , Estudos Transversais , Pandemias , Hipoglicemia/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The goal of this study was to investigate whether preexisting cardiac arrhythmias are associated with adverse obstetrical outcomes in women with a history of open cardiac surgery. STUDY DESIGN: This was a retrospective cohort study of women with a history of open cardiac surgery who delivered at MedStar Washington Hospital Center (Washington, DC) from January 2007 through December 2018. Women with the isolated percutaneous cardiac surgical repair were excluded. Maternal and neonatal outcomes were compared between patients with preexisting cardiac arrhythmias and patients without preexisting cardiac arrhythmias. Maternal outcomes studied were intensive care unit admission, postpartum blood loss greater than 1,000 mL, congestive heart failure development, preeclampsia with severe features, postpartum readmission, postpartum cardiac events, and postpartum length of stay >5 days. Neonatal outcomes investigated were low birth weight <2,500 g, Apgar's scores <7 at 5 minutes, and neonatal intensive care unit admission. Multivariate logistic regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence intervals. RESULTS: The outcomes for 69 deliveries from 56 women with a history of open cardiac surgery were examined. Thirty-three women (48%) had arrhythmias after cardiac surgery with fourteen (20%) requiring implantable cardioverted defibrillators. Two women (6%) with preexisting arrhythmias after cardiac surgery developed postpartum volume overload requiring readmission (p = 0.06). After controlling for age, gestational age at delivery, and BMI, preeclampsia with severe features (p = 0.02) and low birth weight neonates (p = 0.02, aOR = 2.26 [0.56-9.03]) remained statistically more like to occur in patients with preexisting cardiac arrhythmias than in patients without preexisting arrhythmias. CONCLUSION: Women with a history of open cardiac surgery and preexisting cardiac arrhythmias prior to pregnancy are more likely to develop preeclampsia with severe features and have low birth weight neonates compared with women with a history of open cardiac surgery without preexisting cardiac arrhythmias. KEY POINTS: · Preexisting arrhythmias after cardiac surgery was associated with a risk of preeclampsia.. · Neonates of women with preexisting cardiac arrhythmias are more likely to be low birth weight.. · Forty-seven percent of women with open cardiac surgery developed subsequent arrhythmias..
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Pré-Eclâmpsia , Resultado da Gravidez , Gravidez , Recém-Nascido , Humanos , Feminino , Estudos Retrospectivos , Pré-Eclâmpsia/epidemiologia , Unidades de Terapia Intensiva Neonatal , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologiaRESUMO
The question of safety often arises when discussing automated insulin delivery systems, but discussion of safety is often anchored on a comparison to the risk to a person without diabetes, overlooking the risks of living with insulin-requiring diabetes. We should use a net risk safety perspective for evaluating diabetes technology that takes into account the ongoing risks of insulin management for people living with diabetes.
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Diabetes Mellitus Tipo 1 , Pâncreas Artificial , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversosRESUMO
BACKGROUND: Open-source automated insulin delivery (AID) is a user-driven treatment modality used by thousands globally. Healthcare professionals' (HCPs) ability to support users of this technology is limited by a lack of knowledge of these systems. AIMS: To describe the challenges experienced by HCPs supporting participants' use of open-source automated insulin delivery in the Community deRivEd AuTomatEd insulin delivery (CREATE) study. METHODS: Data were collected prospectively from the study team's fortnightly meetings and Slack Workspace (Slack Technologies, Ltd. 2018) during the first 4 months of the trial. Key topics were identified from minutes of meetings. Slack conversations were categorised by topic, with the number of posts per conversation, number of sites per conversation and involvement of experts in open-source AID being recorded. RESULTS: In the first 4 months of the trial, there were 254 conversations in Slack with a mean of 5.2 (±4.25) posts per conversation. The most frequent learning challenge was insulin pump and cannula problems relating to the DANA-iTM insulin pump, which totalled 24.0% of all conversations. Experts on open-source AID use were involved in 83.3% of conversations. CONCLUSIONS: A significant proportion of challenges related to specific devices, rather than AID. Challenges relating to the functioning of open-source AID were more likely to involve input from experts in open-source AID. This is the first report of challenges experienced by a multidisciplinary team in a supported open-source environment that may inform expectations in routine clinical care.
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Diabetes Mellitus Tipo 1 , Pâncreas Artificial , Atenção à Saúde , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
PURPOSE: Idaho's Women's Health Check (WHC) Program provides breast and cervical cancer screening to under- and uninsured women via funding from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Because WHC serves populations with less access to health care, this study evaluated time from breast cancer diagnosis to treatment for women enrolled in the WHC program and linked to Cancer Data Registry of Idaho (CDRI) case data (WHC-linked) and the remainder of female Idaho resident breast cases. METHODS: Among Idaho residents aged 50-64 years diagnosed during 2011-2017 with ductal carcinoma in situ or invasive breast cancer, we assessed differences in the median time from definitive diagnosis to treatment initiation overall and by demographic and tumor characteristics, and differences in the distribution of demographic and tumor-related variables between 231 WHC-linked and 3,040 non-linked breast cancer cases. RESULTS: WHC-linked cases were significantly less likely to be non-Hispanic white, and more likely to live in poorer census tracts, be diagnosed at a later stage, and be treated with mastectomy. Most WHC-linked (92%) and non-linked women (94%) began treatment within 60 days of diagnosis; no differences in time to treatment were observed. CONCLUSION: Disparities in the interval from definitive diagnosis to breast cancer treatment initiation were not observed for women enrolled in the WHC program relative to other Idaho women.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Tempo para o Tratamento/estatística & dados numéricos , Detecção Precoce de Câncer , Feminino , Humanos , Idaho , Programas de Rastreamento , Mastectomia , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros , Fatores Socioeconômicos , Populações Vulneráveis/estatística & dados numéricosRESUMO
BACKGROUND: Automated insulin delivery (AID) systems have been shown to be safe and effective in reducing hyperglycemia and hypoglycemia but are not universally available, accessible, or affordable. Therefore, user-driven open-source AID systems are becoming increasingly popular. OBJECTIVE: This study aims to investigate the motivations for which people with diabetes (types 1, 2, and other) or their caregivers decide to build and use a personalized open-source AID. METHODS: A cross-sectional web-based survey was conducted to assess personal motivations and associated self-reported clinical outcomes. RESULTS: Of 897 participants from 35 countries, 80.5% (722) were adults with diabetes and 19.5% (175) were caregivers of children with diabetes. Primary motivations to commence open-source AID included improving glycemic outcomes (476/509 adults, 93.5%, and 95/100 caregivers, 95%), reducing acute (443/508 adults, 87.2%, and 96/100 caregivers, 96%) and long-term (421/505 adults, 83.3%, and 91/100 caregivers, 91%) complication risk, interacting less frequently with diabetes technology (413/509 adults, 81.1%; 86/100 caregivers, 86%), improving their or child's sleep quality (364/508 adults, 71.6%, and 80/100 caregivers, 80%), increasing their or child's life expectancy (381/507 adults, 75.1%, and 84/100 caregivers, 84%), lack of commercially available AID systems (359/507 adults, 70.8%, and 79/99 caregivers, 80%), and unachieved therapy goals with available therapy options (348/509 adults, 68.4%, and 69/100 caregivers, 69%). Improving their own sleep quality was an almost universal motivator for caregivers (94/100, 94%). Significant improvements, independent of age and gender, were observed in self-reported glycated hemoglobin (HbA1c), 7.14% (SD 1.13%; 54.5 mmol/mol, SD 12.4) to 6.24% (SD 0.64%; 44.7 mmol/mol, SD 7.0; P<.001), and time in range (62.96%, SD 16.18%, to 80.34%, SD 9.41%; P<.001). CONCLUSIONS: These results highlight the unmet needs of people with diabetes, provide new insights into the evolving phenomenon of open-source AID technology, and indicate improved clinical outcomes. This study may inform health care professionals and policy makers about the opportunities provided by open-source AID systems. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/15368.
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Diabetes Mellitus Tipo 1 , Insulina , Adulto , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Motivação , Medidas de Resultados Relatados pelo Paciente , AutorrelatoRESUMO
Chronic inflammatory demyelinating polyneuropathy (CIDP) has a variable clinical course with 15% remaining refractory to treatment. We report a woman with severe refractory CIDP and coexisting chronic lymphocytic leukaemia (CLL) who improved dramatically after chemoimmunotherapy appropriate for the CLL, including rituximab. A subsequent CIDP relapse after 15 months responded again to similar treatment, and the improvement has been maintained with 3-monthly rituximab infusions as sole ongoing therapy. The case suggests that CIDP refractory to conventional treatment may have associated pathology, in this case haematological malignancy, and that treating the malignancy can effectively treat the CIDP.
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BACKGROUND: There is great interest in and excitement about the concept of personalized or precision medicine and, in particular, advancing this vision via various 'big data' efforts. While these methods are necessary, they are insufficient to achieve the full personalized medicine promise. A rigorous, complementary 'small data' paradigm that can function both autonomously from and in collaboration with big data is also needed. By 'small data' we build on Estrin's formulation and refer to the rigorous use of data by and for a specific N-of-1 unit (i.e., a single person, clinic, hospital, healthcare system, community, city, etc.) to facilitate improved individual-level description, prediction and, ultimately, control for that specific unit. MAIN BODY: The purpose of this piece is to articulate why a small data paradigm is needed and is valuable in itself, and to provide initial directions for future work that can advance study designs and data analytic techniques for a small data approach to precision health. Scientifically, the central value of a small data approach is that it can uniquely manage complex, dynamic, multi-causal, idiosyncratically manifesting phenomena, such as chronic diseases, in comparison to big data. Beyond this, a small data approach better aligns the goals of science and practice, which can result in more rapid agile learning with less data. There is also, feasibly, a unique pathway towards transportable knowledge from a small data approach, which is complementary to a big data approach. Future work should (1) further refine appropriate methods for a small data approach; (2) advance strategies for better integrating a small data approach into real-world practices; and (3) advance ways of actively integrating the strengths and limitations from both small and big data approaches into a unified scientific knowledge base that is linked via a robust science of causality. CONCLUSION: Small data is valuable in its own right. That said, small and big data paradigms can and should be combined via a foundational science of causality. With these approaches combined, the vision of precision health can be achieved.
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Interpretação Estatística de Dados , Conjuntos de Dados como Assunto/provisão & distribuição , Medicina de Precisão , Comportamento Cooperativo , Ciência de Dados/métodos , Ciência de Dados/tendências , Conjuntos de Dados como Assunto/normas , Conjuntos de Dados como Assunto/estatística & dados numéricos , Atenção à Saúde/métodos , Atenção à Saúde/estatística & dados numéricos , Ensaios de Triagem em Larga Escala/métodos , Ensaios de Triagem em Larga Escala/estatística & dados numéricos , Humanos , Aprendizagem , Medicina de Precisão/métodos , Medicina de Precisão/estatística & dados numéricos , Análise de Pequenas ÁreasRESUMO
Open source artificial pancreas systems (OpenAPS) have gained considerable interest in the diabetes community. We analyzed continuous glucose monitoring (CGM) records of 80 OpenAPS users with type 1 diabetes (T1D). A total of 19 495 days (53.4 years) of CGM records were available. Mean glucose was 7.6 ± 1.1 mmol/L, time in range 3.9-10 mmol/L was 77.5 ± 10.5%, <3.9 mmol/L was 4.3 ± 3.6%, <3.0 mmol/L was 1.3 ± 1.9%, >10 mmol/L was 18.2 ± 11.0% and > 13.9 mmol/L was 4.1 ± 4.0%, respectively. In 34 OpenAPS users, additional CGM records were obtained while using sensor-augmented pump therapy (SAP). After changing from SAP to OpenAPS, lower mean glucose (-0.6 ± 0.7; P < 0.0001), lower estimated HbA1c (-0.4 ± 0.5%; P < 0.0001), higher time in range 3.9-10 mmol/L (+9.3 ± 9.5%; P < 0.0001), less time < 3.0 mmol/L (-0.7 ± 2.2%; P = 0.0171), lower coefficient of variation (-2.4 ± 5.8; P = 0.0198) and lower mean of daily differences (-0.6 ± 0.9 mmol/L; P = 0.0005) was observed. Glycaemic control using OpenAPS was comparable with results of more rigorously developed and tested AP systems. However, OpenAPS was used by a highly selective, motivated and technology-adept cohort, despite not being approved for the treatment of individuals with T1D.
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Glicemia , Diabetes Mellitus Tipo 1 , Pâncreas Artificial , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Coortes , Bases de Dados Factuais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Hemoglobinas Glicadas/análise , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Pessoa de Meia-Idade , Adulto JovemRESUMO
Exocrine pancreatic insufficiency (EPI) is frequently described as underscreened, underdiagnosed, and undertreated. The treatment for EPI is pancreatic enzyme replacement therapy (PERT), which is costly, and provider confidence in prescribing may be one barrier to reducing undertreatment. The lack of interchangeability studies for prescription PERT and/or lack of efficacy studies of over-the-counter enzyme options may be another barrier. This paper reviewed the prevalence of EPI in the general population and in co-conditions. Prevalence of EPI in the general population is commonly estimated around 10-20%, and further research is needed to evaluate EPI across all age groups and to better understand in which age group EPI becomes more prevalent, as an age effect is often seen in EPI prevalence studies. EPI is perceived to be highly correlated with certain co-conditions, and the majority (~65%) of EPI literature is related to a co-condition such as cystic fibrosis, pancreatitis, post-surgery, cancer, or diabetes. It can be estimated that 85% of literature in identified co-conditions, or 56% of total EPI literature, is on rarer co-conditions which only represent <1% of EPI overall. In contrast, there is very little research and literature on EPI in the general population. The highest absolute rates of EPI with co-conditions are likely diabetes and possibly irritable bowel syndrome with diarrhea, yet they are among the least commonly researched in co-condition and EPI studies. A lack of research on EPI in the general population and in the more common co-conditions may be contributing to the rates of underdiagnosis and underscreening, as well as undertreatment for those with low fecal elastase-1 levels.
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Diabetes Mellitus , Insuficiência Pancreática Exócrina , Pancreatite , Humanos , Prevalência , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/epidemiologia , Insuficiência Pancreática Exócrina/terapia , Pâncreas , Terapia de Reposição de EnzimasRESUMO
OBJECTIVES: To understand behaviors and attitudes of adults with diabetes who read their clinicians' visit notes. METHODS: By linking a large 2017 patient survey involving three institutions with administrative and portal use data, we identified patients with diabetes mellitus from outpatient records and examined reading behaviors related to eligible notes-initial, follow-up, history and physical, and progress notes. We analyzed patients' perceived benefits of reading notes. RESULTS: 2104 respondents had diagnoses of diabetes mellitus and had read ≥1 note in the 12-month period. Patients had an average of 8.7 eligible notes available and read 59% of them. The strongest predictor of reading more notes was having more notes available; the specialties of the authoring clinicians were not correlated with note reading rates. Patients reported understanding notes by primary care clinicians and specialists equally well; more than 90% of patients reported understanding everything or almost everything in a self-selected note. Across visit types, 73-80% of patients reported that note reading was extremely important for taking care of their health. DISCUSSION: People with diabetes want to read their clinicians' notes, are accessing them at high rates, and report understanding the notes and benefiting from reading them.
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Diabetes Mellitus , Leitura , Adulto , Humanos , Registros Eletrônicos de Saúde , Inquéritos e QuestionáriosRESUMO
In the last decade, technology developed by people with diabetes and their loved ones has added to the options for diabetes management. One such example is that of automated insulin delivery (AID) algorithms, which were created and shared as open source by people living with type 1 diabetes (T1D) years before commercial systems were first available. Now, numerous options for commercial systems exist in some countries, yet tens of thousands of people with diabetes are still choosing Open-Source AID (OS-AID), previously called "do-it-yourself" (DIY) systems, which are noncommercial versions of these open-source AID systems. In this article, we provide point and counterpoint perspectives regarding (1) safety and efficacy, (2) regulation and support, (3) user choice and flexibility, (4) access and affordability, and (5) patient and provider education, for open source and commercial AID systems. The perspectives reflected here include that of a person living with T1D who uses and has developed OS-AID systems, a physician-researcher based in the United States who conducts clinical trials to support development of commercial AID systems and supports people with diabetes using all types of AID, and an endocrinologist with T1D who uses both systems and treats people with diabetes using all types of AID.
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Automated insulin delivery (AID) systems enhance glucose management by lowering mean glucose level, reducing hyperglycemia, and minimizing hypoglycemia. One feature of most AID systems is that they allow the user to view "insulin on board" (IOB) to help confirm a recent bolus and limit insulin stacking. This metric, along with viewing glucose concentrations from a continuous glucose monitoring system, helps the user understand bolus insulin action and the future "threat" of hypoglycemia. However, the current presentation of IOB in AID systems can be misleading, as it does not reflect true insulin action or automatic, dynamic insulin adjustments. This commentary examines the evolution of IOB from a bolus-specific metric to its contemporary use in AID systems, highlighting its limitations in capturing real-time insulin modulation during varying physiological states.
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Social behavior deficits are an early-emerging marker of psychopathology and are linked with early caregiving quality. However, the infant neural substrates linking early care to social development are poorly understood. Here, we focused on the infant lateral habenula (LHb), a highly-conserved brain region at the nexus between forebrain and monoaminergic circuits. Despite its consistent links to adult psychopathology, this brain region has been understudied in development when the brain is most vulnerable to environmental impacts. In a task combining social and threat cues, suppressing LHb principal neurons had opposing effects in infants versus juveniles, suggesting the LHb promotes a developmental switch in social approach behavior under threat. We observed that early caregiving adversity (ECA) disrupts typical growth curves of LHb baseline structure and function, including volume, firing patterns, neuromodulatory receptor expression, and functional connectivity with cortical regions. Further, we observed that suppressing cortical projections to the LHb rescued social approach deficits following ECA, identifying this microcircuit as a substrate for disrupted social behavior. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control.
RESUMO
Early caregiving adversity (ECA) is associated with social behavior deficits and later development of psychopathology. However, the infant neural substrates of ECA are poorly understood. The lateral habenula (LHb), a highly conserved brain region with consistent links to adult psychopathology, is understudied in development, when the brain is most vulnerable to environmental impacts. Here, we describe the structural and functional ontogeny of the LHb and its behavioral role in infant and juvenile rat pups. We show that the LHb promotes a developmental transition in social approach behavior under threat as typically reared infants mature. By contrast, we show that ECA disrupts habenular ontogeny, including volume, protein expression, firing properties, and corticohabenular connectivity. Furthermore, inhibiting a specific corticohabenular projection rescues infant social approach deficits following ECA. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control.