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1.
BMJ Open ; 13(1): e063161, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631237

RESUMO

INTRODUCTION: Insulin therapy plays an irreplaceable role in glycaemic control among older adults with type 2 diabetes mellitus (T2DM) and can be administered by either multiple daily injections (MDI) of insulin or by a continuous subcutaneous insulin infusion (CSII) pump. Many clinical trials have compared the effects of CSII pumps and MDI in various diabetic populations, but there has been no systematic review and meta-analysis focusing on older adults with T2DM. This study aims to determine whether the CSII pump is associated with better glycaemic control relative to the MDI in older adults with T2DM. METHODS AND ANALYSIS: PubMed, Medline, Cochrane Library, Web of Science core collection, China National Knowledge Infrastructure (CNKI), Wan Fang Database, Chinese Science and Technology Journal Database (VIP) and Chinese Biomedical Literature Database (SinoMed) will be searched from inception to December 2021. Only randomised controlled trials will be included, and the language of the selected studies will be restricted to English and Chinese. Two researchers will independently screen the studies, extract data, assess the risk of bias and evaluate the quality of evidence. Any disagreement will be resolved by consensus or by a third researcher. Data analysis and synthesis will be conducted using RevMan V.5.3. Subgroup analysis, sensitivity analysis and publication bias assessment will be performed, as necessary. ETHICS AND DISSEMINATION: As this study will not contain personal information, ethical approval will not be required. The results of the study will be published in a peer-reviewed journal or at relevant conference. PROSPERO REGISTRATION NUMBER: CRD42021283729.


Assuntos
Diabetes Mellitus Tipo 2 , Infusões Subcutâneas , Injeções Subcutâneas , Insulina , Idoso , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico , Insulina/administração & dosagem , Insulina/uso terapêutico , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Infusões Subcutâneas/métodos , Injeções Subcutâneas/métodos , Sistemas de Infusão de Insulina , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Curr Opin Allergy Clin Immunol ; 22(6): 371-379, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36165464

RESUMO

PURPOSE OF REVIEW: Welsh immunodeficient patients on immunoglobulin replacement therapy (IgRT) who were considered high risk for severe coronavirus disease 2019 (COVID-19) were directed to shield. Consequently, patients receiving hospital-based intravenous immunoglobulin (IVIg) quickly transitioned to home-based self-administered subcutaneous immunoglobulin (SCIg). This evaluation aimed to assess patients' perceptions and experiences and laboratory outcomes of emergency IgRT transition during COVID-19. RECENT FINDINGS: A quick transition from in-hospital IVIg to home-based rapid push SCIg is achievable, however, patient IgRT administration preference remains key outside of emergency shielding measures. SUMMARY: Subjective self-reported experiences ( n  = 23) and objective immunoglobulin G (IgG) concentration ( n  = 28) assessments were prospectively collected from patients pre/post-IgRT switch. In total, 41/55 (75%) patients transitioned from IVIg to rapid push SCIg and all completed training to self-administer subcutaneously within 24 days. Twenty-two percent ( n  = 5) of patients preferred SCIg and 35% ( n  = 8) wanted to return to hospital-based IVIg at 6 weeks post-transition. Mean IgG levels were similar pre vs. post-SCIg switch (10.3 g/l vs. 10.6 g/l, respectively). Patients reported greater infection anxiety during COVID-19 and adapted behaviours to mitigate risk. Although a third of patients wished to return to IVIg following cessation of shielding, over time the percentage electing to remain on SCIg rose from 22% to 59%.


Assuntos
COVID-19 , Síndromes de Imunodeficiência , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , COVID-19/terapia , Síndromes de Imunodeficiência/terapia , Imunoglobulina G/uso terapêutico , Avaliação de Resultados da Assistência ao Paciente , Infusões Subcutâneas
3.
Rev Neurol ; 74(11): 367-371, 2022 06 01.
Artigo em Espanhol | MEDLINE | ID: mdl-35635363

RESUMO

INTRODUCTION: Dysexecutive disorder and apathy are characteristic symptoms of frontal dysfunction linked to Parkinson's disease. The effect of continuous subcutaneous apomorphine infusion is not known in detail. DEVELOPMENT: A search for the most relevant studies published to date in this field was carried out, along with their analysis. Apomorphine achieves improvements in tests that measure tasks such as planning, attention, verbal fluency and apathy. CONCLUSIONS: Due to its distinctive pharmacological profile, with enhanced activity on D1-type dopaminergic receptors, apomorphine may have beneficial effects on the frontal dysfunction produced by the disease.


TITLE: Apomorfina y disfunción frontal en la enfermedad de Parkinson.Introducción. El trastorno disejecutivo y la apatía son síntomas característicos de la disfunción frontal ligada a la enfermedad de Parkinson. El efecto de la infusión continua subcutánea de apomorfina en la disfunción frontal no se conoce con detalle. Desarrollo. Se ha realizado una búsqueda y análisis de los trabajos publicados más relevantes en este campo. La apomorfina logra mejorías en las pruebas que miden tareas como la planificación, la atención, la fluencia verbal y la apatía. Conclusiones. Debido a su perfil farmacológico distintivo, con mayor actividad sobre los receptores dopaminérgicos de tipo D1, la apomorfina puede resultar beneficiosa en la disfunción frontal de la enfermedad.


Assuntos
Apomorfina , Doença de Parkinson , Apomorfina/farmacologia , Apomorfina/uso terapêutico , Humanos , Infusões Subcutâneas , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico
4.
Int J Med Inform ; 163: 104777, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35483130

RESUMO

OBJECTIVES: To assess the impact of electronically prescribed mixed-drug infusions on the prevalence and types of prescription errors and staff time. DESIGN, SETTING AND PARTICIPANTS: Before-and-after study on acute medical wards of a large UK teaching hospital, utilising patient and staff data from the assessed wards. INTERVENTION: Electronically-generated mixed-drug infusions. MAIN OUTCOME MEASURES: (1) Rate of prescription errors (divided into errors of commission and omission); (2) time taken to process patient discharge prescriptions containing a mixed-drug infusion; and (3) time between prescription and administration of mixed-drug infusions. RESULTS: 100 errors of omission were detected pre-intervention, whilst none were detected post intervention. 6 errors of commission were identified at baseline, whilst 2 were highlighted post intervention (p = 0.149). 14 physicochemically incompatible infusions were prescribed at baseline, post-intervention all infusions were compatible (p < 0.01). Time spent processing discharge prescriptions fell from 60 min (SME±1.7) to 26 min (SME± 2.7; p < 0.01). The median time from prescription to administration reduced from 120 min (95 % CI 106-150) to 65 min (95 % CI 43-85; p < 0.01). CONCLUSIONS: The intervention eliminated errors of omission and facilitated the prescribing of compatible multicomponent infusions. Electronically prescribed mixed-drug infusions also reduced both the time taken to complete discharge prescriptions and the time taken to commence such infusions.


Assuntos
Prescrição Eletrônica , Prescrições de Medicamentos , Humanos , Infusões Subcutâneas , Alta do Paciente , Segurança do Paciente
6.
Parkinsonism Relat Disord ; 97: 68-72, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35339102

RESUMO

INTRODUCTION: The objective of this study was to compare the pharmacokinetics (PK) of levodopa (LD) from 24-h continuous subcutaneous infusion of foslevodopa/foscarbidopa to the LD pharmacokinetics from 16-h levodopa-carbidopa intestinal gel (LCIG) followed by night-time oral LD/carbidopa (CD) doses. METHODS: This was a Phase 1, open-label, randomized, 2-period crossover study conducted in 25 male and female healthy volunteers. RESULTS: The LD exposures (Cmax0-16, AUC0-16 and AUC∞) following subcutaneous infusion of 700/35 mg foslevodopa/foscarbidopa over 24 h were similar (<8% difference) to those of LCIG 350/87.5 mg LD/CD administered over 16 h followed by two 100/25 mg LD/CD oral doses at 18 and 21 h after the start of LCIG delivery. CONCLUSION: Foslevodopa/foscarbidopa subcutaneous infusion provides levodopa exposures comparable to LCIG throughout the day. GOV IDENTIFIER: Not Applicable.


Assuntos
Carbidopa , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Estudos Cross-Over , Agonistas de Dopamina/uso terapêutico , Combinação de Medicamentos , Feminino , Géis/uso terapêutico , Humanos , Infusões Subcutâneas , Jejuno , Levodopa , Masculino , Doença de Parkinson/tratamento farmacológico
7.
Immunotherapy ; 14(5): 373-387, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35128932

RESUMO

Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) as initial immunoglobulin (IG)-replacement therapy for patients with primary immunodeficiency diseases (PID). Methods: We systematically identified and summarized literature in MEDLINE, Embase, BioSciences Information Service and Cochrane Library assessing efficacy/effectiveness, safety/tolerability, health-related quality-of-life (HRQoL) and dosing regimens of SCIG for IG-naive patients with PID. Results: Sixteen studies were included. In IG-naive patients, SCIG managed/reduced infections and demonstrated similar pharmacokinetic parameters to IG-experienced patients; adverse events were mostly minor injection-site pain or discomfort. Three studies reported improvements in HRQoL. Quality of studies was difficult to assess due to limited reporting. Conclusion: Although studies were lacking, available data suggest IG-naive and IG-experienced patients initiating SCIG likely have similar outcomes.


Assuntos
Imunoglobulinas , Síndromes de Imunodeficiência , Humanos , Imunização Passiva , Imunoglobulinas/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Infusões Subcutâneas , Injeções Subcutâneas , Qualidade de Vida
8.
Clin Immunol ; 236: 108938, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35121105

RESUMO

Many patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT). In a multicenter, randomized, open-label, crossover, non-inferiority 3-month-trial, we compared the impact of the subcutaneous immunoglobulin Gammanorm® administered via pump or syringe (rapid push). Primary endpoint was the life quality index (LQI), secondary endpoints were QoL (SF36v2), satisfaction (TSQM-11), disease and treatment burden (PRISM), incidence of infections and adverse events (AE), treatment costs, and IgG levels. 28/30 patients completed the study. Most of the endpoints were comparable. Drug administrations with rapid push were more frequent, but reduced total time expenditure and some costs. Of the TSQM-11/LQI/SF36 components only "treatment interference with daily activities" was superior with pump and two QoL domains with rapid push. Both delivery devices showed favorable safety. Rapid push was preferred by 34.5% of patients. It proved to be an efficacious and cost-effective alternative to pumps adding to patient choice and increasing flexibility during long-term IgRT.


Assuntos
Síndromes de Imunodeficiência , Qualidade de Vida , Adulto , Humanos , Imunização Passiva , Imunoglobulina G , Síndromes de Imunodeficiência/terapia , Infusões Subcutâneas
9.
Immunotherapy ; 14(4): 259-270, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34986666

RESUMO

Most primary immunodeficiency diseases, and select secondary immunodeficiency diseases, are treated with immunoglobulin (IG) therapy, administered intravenously or subcutaneously (SCIG). The first instance of IG replacement for primary immunodeficiency disease was a 16.5% formulation administered subcutaneously in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG replacement therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.


Plain language summary Primary immunodeficiency diseases, and select secondary immunodeficiency diseases, weaken the immune system, allowing infections and other health problems to occur more easily. Some patients require treatments to boost their immune system, such as immunoglobulin (IG) therapy, which can be either injected via a needle into a vein (intravenously) or inserted underneath the skin (subcutaneously; SCIG). The first instance of IG treatment for primary immunodeficiency disease was a 16.5% SCIG product given in 1952. While most SCIG products are now a 10 or 20% concentration, this review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG therapy, as well as key characteristics, manufacturing and clinical studies. In determining an appropriate IG regimen, one must consider specific patient needs, characteristics and preferences. There are advantages to SCIG, such as stable serum immunoglobulin G levels, high tolerability and the flexibility of self-administered home treatment.


Assuntos
Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/imunologia , Síndromes de Imunodeficiência/imunologia , Infusões Subcutâneas , Injeções Subcutâneas , Resultado do Tratamento
10.
Diabet Med ; 39(5): e14793, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35034388

RESUMO

AIMS: The use of do-it-yourself artificial pancreas systems (DIYAPS) among people with type 1 diabetes is increasing. At present, it is unclear how DIYAPS compares with other technologies such as FreeStyle Libre (FSL) and continuous subcutaneous insulin infusion (CSII). The aim of this analysis is to compare safety, effectiveness and quality-of-life outcomes of DIYAPS use with the addition of FSL to CSII. METHOD: Data from two large UK hospitals were extracted from the Association of British Clinical Diabetologists (ABCD) DIYAPS and FSL audits. Outcomes included HbA1c , glucose TBR (time-below-range), TIR (time-in-range), Diabetes Distress Score (DDS), and Gold hypoglycaemia score. Any adverse events were noted. Changes at follow-up were assessed using paired t-tests and ANOVA in Stata; TIR/TBR at follow-up assessed using unpaired t-tests; chi-square tests assessed the change in frequency of health utilisation (e.g. hospital admissions). RESULTS: DIYAPS (n = 35) and FSL+CSII (n = 149) users, with median follow-up duration of 1.4 (IQR 0.8-2.1) and 1.3 (IQR 0.7-1.8) years, respectively, were included. HbA1c with DIYAPS use changed by -10 mmol/mol [0.9%] (p < 0.001, 95% CI 5, 14 [0.5, 1.3%]) significantly lower (p < 0.001) than in the FSL+CSII group -3 mmol/mol [0.25%] (p < 0.001, 95% CI 1, 4 [0.1, 0.4%]). TIR was higher and TBR was lower in the DIYAPS group. Adverse events were rare in both groups and no significant differences were observed in the frequency of healthcare utilisation. CONCLUSION: DIYAPS use was associated with a lower HbA1c levels, higher TIR and lower TBR compared with FSL+CSII. There was no significant increase in adverse events, although this should be interpreted cautiously given the low numbers of users. Full results from the ABCD DIYAPS audit are awaited.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Pâncreas Artificial , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Infusões Subcutâneas , Insulina/uso terapêutico , Sistemas de Infusão de Insulina
11.
Med J Malaysia ; 77(1): 95-97, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35087003

RESUMO

We report a clinical and laboratory observation in a boy with X-linked agammaglobulinemia (XLA) who underwent an immunoglobulin replacement therapy (IRT) via the subcutaneous route (IGSC) seven years after his IRT via intravenous route (IGIV). He was free of invasive infections when on IGIV but not the troublesome coughs a week before the next infusion. A switch to a subcutaneous route resulted in significant improvement of symptoms with good weight gain. When on 2-weekly IGSC cycle, adjusting dose for weight resulted in an IgG trough level of > 600 mg/dl.


Assuntos
Agamaglobulinemia , Doenças Genéticas Ligadas ao Cromossomo X , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/tratamento farmacológico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/tratamento farmacológico , Humanos , Imunoglobulina G/uso terapêutico , Infusões Subcutâneas , Masculino
12.
J Clin Immunol ; 42(3): 500-511, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34973143

RESUMO

PURPOSE: The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). METHODS: Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject's previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. RESULTS: Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12-16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008-0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83-1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. CONCLUSIONS: IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.


Assuntos
Síndromes de Imunodeficiência , Adolescente , Adulto , Criança , Humanos , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Infusões Subcutâneas
13.
BMJ Support Palliat Care ; 12(e6): e763-e766, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32647034

RESUMO

BACKGROUND: In chronic heart failure many patients have recurrent hospital admissions and it is the leading cause of admission in people aged over 65 years. In those with end-stage heart failure, there is limited evidence that furosemide can be given subcutaneously to relieve symptoms and avoid hospital admission. METHOD: We initiated a community-based continuous subcutaneous infusion (CSCI) furosemide service for the treatment of advanced heart failure. We aimed to increase patient choice, offer an alternative to hospital admission and, in patients at the end of their life, allow them to die at their preferred place of care with symptom alleviation. We retrospectively reviewed case notes. RESULTS: 36 consecutive episodes of CSCI of treatment were recorded in 28 patients. 15 patients (54%) survived beyond the initial treatment course with 13 patients (87%) avoiding acute hospital admission. There was a reduction in mean hospital admission rates from 2.87 to 0.73 (p<0.001) in the 6-month periods either side of the first episode of CSCI furosemide. A median reduction of 4 kg weight loss was recorded. 13 patients died during the initial treatment course. 12 (92%) died at home and 1 died at the hospital palliative care unit. All had symptoms controlled. CONCLUSION: Subcutaneous furosemide can be successfully delivered in the community. In addition to palliation in the final days of life, community subcutaneous furosemide can be an effective treatment leading to weight loss and improved symptoms with survival for several months.


Assuntos
Furosemida , Insuficiência Cardíaca , Humanos , Idoso , Furosemida/uso terapêutico , Diuréticos , Estudos Retrospectivos , Insuficiência Cardíaca/tratamento farmacológico , Infusões Subcutâneas , Redução de Peso
14.
J Clin Endocrinol Metab ; 107(2): e767-e782, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34460933

RESUMO

CONTEXT: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis and are thought to contribute to the glucose-lowering effects of bariatric surgery. OBJECTIVE: To establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY (tripeptide GOP) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). DESIGN AND SETTING: Subanalysis of a single-blind, randomized, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. PATIENTS AND INTERVENTIONS: Twenty-five obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n = 14) or 0.9% saline control (n = 11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. MAIN OUTCOME MEASURES: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modeling approaches to identify similarities and differences between the effects of each intervention. RESULTS: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. CONCLUSIONS: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.


Assuntos
Restrição Calórica/estatística & dados numéricos , Diabetes Mellitus Tipo 2/terapia , Derivação Gástrica/estatística & dados numéricos , Hormônios Gastrointestinais/administração & dosagem , Obesidade Mórbida/terapia , Adulto , Idoso , Glicemia/análise , Restrição Calórica/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/urina , Quimioterapia Combinada/métodos , Feminino , Derivação Gástrica/métodos , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Humanos , Infusões Subcutâneas , Masculino , Metabolômica/estatística & dados numéricos , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/metabolismo , Obesidade Mórbida/urina , Oxintomodulina/administração & dosagem , Peptídeo YY/administração & dosagem , Método Simples-Cego , Resultado do Tratamento , Redução de Peso , Adulto Jovem
15.
J Cardiovasc Transl Res ; 15(3): 644-652, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34642870

RESUMO

We aimed to evaluate the efficacy (short-term changes in surrogates of decongestion) and safety following the ambulatory administration of subcutaneous furosemide (SCF) in patients with WHF. Fifty-five ambulatory patients were treated with SCF administered by an elastomeric pump for at least 72 h. Surrogates of congestion were assessed at baseline, 72 h, and 30 days. Spot urinary sodium (uNa+) was assessed at baseline, 24-48-72 h, and 30 days. The median (IQI) of NT-proBNP and uNa+ at baseline was 5218 pg/mL (2856-10878) and 68±3 mmol/L, respectively. Following administration of SCF (median dose of 100 mg/daily), we found a sustained increase in uNa+ during the first 72 h of treatment compared to baseline, paralleled with evidence of decongestion at 72 h, and 30 days. No significant safety concerns were observed. SCF was an effective and safe diuretic strategy for outpatient congestion management. Non-formulated subcutaneous furosemide in patients with WHF. Efficacy and safety.


Assuntos
Furosemida , Insuficiência Cardíaca , Diuréticos/efeitos adversos , Furosemida/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Infusões Subcutâneas , Resultado do Tratamento
16.
J Clin Immunol ; 42(1): 64-71, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34617265

RESUMO

PURPOSE: The aim was to review the compliance, side effects and effectiveness of subcutaneous immunoglobulin (SCIG) supplementation in patients with primary immunodeficiencies (PID) who had previously received intravenous immunoglobulin (IVIG) therapy and subsequently switched to SCIG, as well as to compare these parameters in patients while considering body weight. METHODS: Demographic data, clinical and laboratory findings, SCIG dose, and side effects of 87 patients were retrospectively obtained from patient files. In patients who first received IVIG and then SCIG, the monthly SCIG dose was calculated by multiplying the IVIG dose by 1.37. The total monthly SCIG dose was distributed via injection across three or four doses per month, thus every 7 or 10 days. RESULTS: Of the 87 patients aged between one and 22 years, 50 were male (57.5%) and 37 were female (42.5%). The serum IgG levels of the SCIG group were higher and more stable than those of the IVIG group. The number of hospitalizations and infections decreased significantly after initiation of SCIG. Thirteen patients (14.9%) had low body weight (LBW) for their age, seven of whom were male (53.8%). Serum IgG levels of the LBW cohort were significantly elevated and more stable during the SCIG period than the IVIG period. Mild, local side effects were detected in 153 administrations (3.3%) in 30 patients with normal body weight, while no local reactions were recorded in the patients with LBW. CONCLUSION: SCIG supplementation is an effective treatment for pediatric patients with PID. The preliminary data from the present study suggest that such treatment is also safe for LBW children. The numbers of patient hospitalizations and family visits to clinics were reduced, allowing our patients and their parents to live more normal lives.


Assuntos
Peso Corporal Ideal , Síndromes de Imunodeficiência , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imunização Passiva , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Lactente , Infusões Subcutâneas , Masculino , Estudos Retrospectivos , Adulto Jovem
17.
J Clin Oncol ; 40(1): 40-51, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34388022

RESUMO

PURPOSE: Proteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM. METHODS: We conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for phase II was overall response rate (ORR [≥ minimal response]) after induction. RESULTS: A total of 59 patients were enrolled (median age, 69 years; range, 46-91 years). Median number of prior treatments was 2 (range, 1-7); 70% had an intermediate or high WM-IPSS (International Prognostic Scoring System for WM) score. After eight cycles, ORR was 71% (42 out of 59) (14% very good partial response [PR], 37% PR, and 20% minor response). Depth of response improved until month 12 (best ORR 85% [50 out of 59]: 15% very good PR, 46% PR, and 24% minor response). Median duration of response was 36 months. The average hematocrit level increased significantly (0.33-0.38 L/L) after induction (P < .001). After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decreased significantly (median 3,700-2,700 mg/dL, P < .0001). Median time to first response was 4 months. Median progression-free survival and overall survival were not reached. After median follow-up of 24 months (range, 7.4-54.3 months), progression-free survival and overall survival were 56% and 88%, respectively. Toxicity included mostly grade 2 or 3 cytopenias, grade 1 or 2 neurotoxicity, and grade 2 or 3 infections. No infusion-related reactions or immunoglobulin M flare occurred with use of subcutaneous rituximab. Quality of life improved significantly after induction. In total, 48 patients (81%) completed at least six cycles of IRD. CONCLUSION: Combination of IRD shows promising efficacy with manageable toxicity in patients with relapsed or refractory WM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos de Boro/administração & dosagem , Dexametasona/administração & dosagem , Glicina/análogos & derivados , Inibidores de Proteassoma/administração & dosagem , Rituximab/administração & dosagem , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Boro/efeitos adversos , Dexametasona/efeitos adversos , Europa (Continente) , Estudos de Viabilidade , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteassoma/efeitos adversos , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico
18.
Purinergic Signal ; 18(1): 13-59, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34757513

RESUMO

Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine.


Assuntos
Trifosfato de Adenosina/metabolismo , COVID-19/imunologia , Síndrome da Liberação de Citocina/etiologia , Inflamação/etiologia , Lidocaína/uso terapêutico , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Receptores Purinérgicos/fisiologia , Anti-Inflamatórios/uso terapêutico , Cuidados Críticos , Síndrome da Liberação de Citocina/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Infusões Subcutâneas , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Linfonodos/imunologia , Sistema Linfático/imunologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Modelos Imunológicos , Antagonistas do Receptor Purinérgico P2X/administração & dosagem , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos/efeitos dos fármacos , Receptores Purinérgicos P1/efeitos dos fármacos , Receptores Purinérgicos P1/fisiologia , Receptores Purinérgicos P2X7/fisiologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Transdução de Sinais , Linfócitos T Reguladores/imunologia
19.
Nat Med ; 28(1): 89-95, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34873344

RESUMO

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) injected periodically have been shown to not increase and, for some members of this class, decrease the risk of cardiovascular events. The cardiovascular safety of delivering a continuous subcutaneous infusion of the GLP-1RA exenatide (ITCA 650) is unknown. Here, we randomly assigned patients with type 2 diabetes with, or at risk for, atherosclerotic cardiovascular disease (ASCVD) to receive ITCA 650 or placebo to assess cardiovascular safety in a pre-approval trial ( NCT01455896 ). The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina. On the basis of 2008 guidance from the US Food and Drug Administration, a non-inferiority margin of 1.8 for the upper bound of the 95% confidence interval (CI) of the hazard ratio (HR) was used. We randomized 4,156 patients (2,075 assigned to receive ITCA 650 and 2,081 assigned to receive placebo) who were followed for a median of 16 months. The primary outcome occurred in 4.6% (95/2,075) of patients in the ITCA 650 group and 3.8% (79/2,081) of patients in the placebo group, meeting the pre-specified non-inferiority criterion (HR = 1.21, 95% CI, 0.90-1.63, Pnon-inferiority = 0.004). Serious adverse events were similar between the two groups. Adverse events were more frequent in the ITCA 650 group (72%, 1,491/2,074) than in the placebo group (63.9%, 1,325/2,070), mainly due to an increase in gastrointestinal events and disorders while on ITCA 650. In patients with type 2 diabetes with, or at risk for, ASCVD, ITCA 650 was non-inferior to placebo. A larger and longer-duration cardiovascular outcomes trial is needed to define more precisely the cardiovascular effects of ITCA 650 in this population.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida/administração & dosagem , Hipoglicemiantes/administração & dosagem , Idoso , Exenatida/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
20.
Arch Pediatr ; 29(1): 27-29, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34955306

RESUMO

AIM: The COVID-19 pandemic has forced governments to impose lockdown policies, thus impacting patients with chronic diseases, such as type 1 diabetes. The aim of this study was to evaluate the impact of lockdown on glycemic control in type 1 diabetes patients. PATIENTS AND METHODS: We retrospectively evaluated patients using a continuous subcutaneous insulin infusion device during the nationwide lockdown. Children and adolescents aged 2-18 years followed up at the Pediatric Endocrinology Unit of Hospitalar São João in Portugal were included in the study. We collected data on the age, weight, insulin doses, and glycemic control of the patients before and after the restrictions. RESULTS: The study included 100 patients, 59 males, with a mean age of 12.5 years. Baseline data showed a suboptimal glycemic control with a median HbA1c of 7.9%. The lockdown was associated with an increase in the body mass index (BMI) of all patients (p = 0.009), particularly girls and older teenagers. Metabolic control deteriorated in the 10-13 age group (p = 0.03), with a 0.4% increase in HbA1c. CONCLUSION: To date, this is the largest study on the impact of lockdown on type 1 diabetes in patients using an insulin pump. The results highlight the importance of physical activity, parental supervision, and continuation of healthcare assistance through telemedicine in young individuals with type 1 diabetes.


Assuntos
COVID-19/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico/métodos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Pandemias/prevenção & controle , Quarentena , Adolescente , Glicemia , COVID-19/epidemiologia , Criança , Controle de Doenças Transmissíveis/métodos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , /metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Infusões Subcutâneas , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Portugal/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
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