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1.
Artículo en Inglés | MEDLINE | ID: mdl-38829767

RESUMEN

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

3.
Brain Inj ; 38(8): 652-658, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38555516

RESUMEN

INTRODUCTION: Bromocriptine is a dopamine receptor agonist used for central hyperthermia with limited data. We describe our single-center experience utilizing bromocriptine for central hyperthermia, including the population treated, most common dosing regimens, adverse events, and discontinuation reasons. METHODS: A retrospective study was conducted screening patients who were admitted to intensive care units for acute neurological insults and administered bromocriptine for central hyperthermia between April 2016 and September 2022. Baseline characteristics, disease severity markers, and bromocriptine doses were collected. Body temperatures prior to the first dose of bromocriptine, at the time of dose, and after each dose were recorded. Co-administration of additional hyperthermia management therapies was noted. RESULTS: Thirty patients were included. The most common diagnosis was traumatic brain injury (TBI) (N = 14). The most common reason for discontinuation was resolution of indication (N = 14). Discontinuation due to mild adverse effects occurred in four patients; hepatotoxicity was the most common. There was a paired mean difference of -0.37°C (p = 0.005) between temperatures before and after bromocriptine initiation. CONCLUSION: Bromocriptine is a potential therapy for the management of central hyperthermia in patients with severe acute neurologic insults who have failed other therapies. Bromocriptine was well tolerated and associated with a low incidence of adverse events.


Asunto(s)
Bromocriptina , Agonistas de Dopamina , Humanos , Bromocriptina/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Agonistas de Dopamina/uso terapéutico , Agonistas de Dopamina/administración & dosificación , Anciano , Lesiones Encefálicas , Hipertermia/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/complicaciones , Resultado del Tratamiento , Adulto Joven
5.
J Am Coll Cardiol ; 83(2): 291-299, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38199706

RESUMEN

BACKGROUND: Exercise electrocardiographic stress testing (EST) has historically been validated against the demonstration of obstructive coronary artery disease. However, myocardial ischemia can occur because of coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease. OBJECTIVES: The aim of this study was to assess the specificity of EST to detect an ischemic substrate against the reference standard of coronary endothelium-independent and endothelium-dependent microvascular function in patients with angina with nonobstructive coronary arteries (ANOCA). METHODS: Patients with ANOCA underwent invasive coronary physiological assessment using adenosine and acetylcholine. CMD was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol, with ischemia defined as the appearance of ≥0.1-mV ST-segment depression 80 ms from the J-point on electrocardiography. The study was powered to detect specificity of ≥91%. RESULTS: A total of 102 patients were enrolled (65% women, mean age 60 ± 8 years). Thirty-two patients developed ischemia (ischemic group) during EST, whereas 70 patients did not (nonischemic group); both groups were phenotypically similar. Ischemia during EST was 100% specific for CMD. Acetylcholine flow reserve was the strongest predictor of ischemia during exercise. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of EST dropped to 0%. CONCLUSIONS: In patients with ANOCA, ischemia on EST was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.


Asunto(s)
Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Enfermedades Vasculares , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Prueba de Esfuerzo , Enfermedad de la Arteria Coronaria/diagnóstico , Acetilcolina , Electrocardiografía , Isquemia Miocárdica/diagnóstico , Isquemia
6.
Circ Cardiovasc Interv ; 17(1): e013657, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37929596

RESUMEN

BACKGROUND: Myocardial bridges (MBs) are prevalent and can be associated with acute and chronic ischemic syndromes. We sought to determine the substrates for ischemia in patients with angina with nonobstructive coronary arteries and a MB in the left anterior descending artery. METHODS: Patients with angina with nonobstructive coronary arteries underwent the acquisition of intracoronary pressure and flow during rest, supine bicycle exercise, and adenosine infusion. Coronary wave intensity analysis was performed, with perfusion efficiency defined as accelerating wave energy/total wave energy (%). Epicardial endothelial dysfunction was defined as a reduction in epicardial vessel diameter ≥20% in response to intracoronary acetylcholine infusion. Patients with angina with nonobstructive coronary arteries and a MB were compared with 2 angina with nonobstructive coronary arteries groups with no MB: 1 with coronary microvascular disease (CMD: coronary flow reserve, <2.5) and 1 with normal coronary flow reserve (reference: coronary flow reserve, ≥2.5). RESULTS: Ninety-two patients were enrolled in the study (30 MB, 33 CMD, and 29 reference). Fractional flow reserve in these 3 groups was 0.86±0.05, 0.92±0.04, and 0.94±0.05; coronary flow reserve was 2.5±0.5, 2.0±0.3, and 3.2±0.6. Perfusion efficiency increased numerically during exercise in the reference group (65±9%-69±13%; P=0.063) but decreased in the CMD (68±10%-50±10%; P<0.001) and MB (66±9%-55±9%; P<0.001) groups. The reduction in perfusion efficiency had distinct causes: in CMD, this was driven by microcirculation-derived energy in early diastole, whereas in MB, this was driven by diminished accelerating wave energy, due to the upstream bridge, in early systole. Epicardial endothelial dysfunction was more common in the MB group (54% versus 29% reference and 38% CMD). Overall, 93% of patients with a MB had an identifiable ischemic substrate. CONCLUSIONS: MBs led to impaired coronary perfusion efficiency during exercise, which was due to diminished accelerating wave energy in early systole compared with the reference group. Additionally, there was a high prevalence of endothelial and microvascular dysfunction. These ischemic mechanisms may represent distinct treatment targets.


Asunto(s)
Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Angina Microvascular , Isquemia Miocárdica , Humanos , Circulación Coronaria , Resultado del Tratamiento , Vasos Coronarios/diagnóstico por imagen , Isquemia , Microcirculación , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Isquemia Miocárdica/diagnóstico
7.
Circulation ; 149(1): 36-47, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-37905403

RESUMEN

BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.


Asunto(s)
Enfermedad de la Arteria Coronaria , Angina Microvascular , Isquemia Miocárdica , Femenino , Humanos , Masculino , Amlodipino/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Circulación Coronaria , Estudios Cruzados , Microcirculación , Fenotipo , Ranolazina/uso terapéutico , Persona de Mediana Edad , Anciano
8.
JAMIA Open ; 6(4): ooad101, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38058680

RESUMEN

Objectives: A lack of pharmacist-specific risk-stratification scores in the electronic health record (EHR) may limit resource optimization. The medication regimen complexity-intensive care unit (MRC-ICU) score was implemented into our center's EHR for use by clinical pharmacists. The purpose of this evaluation was to evaluate MRC-ICU as a predictor of pharmacist workload and to assess its potential as an additional dimension to traditional workload measures. Materials and methods: Data were abstracted from the EHR on adult ICU patients, including MRC-ICU scores and 2 traditional measures of pharmacist workload: numbers of medication orders verified and interventions logged. This was a single-center study of an EHR-integrated MRC-ICU tool. The primary outcome was the association of MRC-ICU with institutional metrics of pharmacist workload. Associations were assessed using the initial 24-h maximum MRC-ICU score's Pearson's correlation with overall admission workload and the day-to-day association using generalized linear mixed-effects modeling. Results: A total of 1205 patients over 5083 patient-days were evaluated. Baseline MRC-ICU was correlated with both cumulative order volume (Spearman's rho 0.41, P < .001) and cumulative interventions placed (Spearman's rho 0.27, P < .001). A 1-point increase in maximum daily MRC-ICU was associated with a 31% increase in order volume (95% CI, 24%-38%) and 4% increase in interventions (95% CI, 2%-5%). Discussion and conclusion: The MRC-ICU is a validated score that has been previously correlated with important patient-centered outcomes. Here, MRC-ICU was modestly associated with 2 traditional objective measures of pharmacist workload, including orders verified and interventions placed, which is an important step for its use as a tool for resource utilization needs.

9.
Int J Mol Sci ; 24(20)2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37894881

RESUMEN

Nitric oxide (NO) plays an important and diverse signalling role in the cardiovascular system, contributing to the regulation of vascular tone, endothelial function, myocardial function, haemostasis, and thrombosis, amongst many other roles. NO is synthesised through the nitric oxide synthase (NOS)-dependent L-arginine-NO pathway, as well as the nitrate-nitrite-NO pathway. The three isoforms of NOS, namely neuronal (NOS1), inducible (NOS2), and endothelial (NOS3), have different localisation and functions in the human body, and are consequently thought to have differing pathophysiological roles. Furthermore, as we continue to develop a deepened understanding of the different roles of NOS isoforms in disease, the possibility of therapeutically modulating NOS activity has emerged. Indeed, impaired (or dysfunctional), as well as overactive (or dysregulated) NOS activity are attractive therapeutic targets in cardiovascular disease. This review aims to describe recent advances in elucidating the physiological role of NOS isoforms within the cardiovascular system, as well as mechanisms of dysfunctional and dysregulated NOS in cardiovascular disease. We then discuss the modulation of NO and NOS activity as a target in the development of novel cardiovascular therapeutics.


Asunto(s)
Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/terapia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa/metabolismo , Miocardio/metabolismo , Isoformas de Proteínas/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo
10.
Neurohospitalist ; 13(4): 434-437, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37701253

RESUMEN

Clobazam is a 1,5-benzodiazepine frequently used as an adjunctive agent for refractory seizures and status epilepticus. Clobazam undergoes metabolism to an active metabolite norclobazam which is subsequently hydroxylated by CYP2C19, a cytochrome with several pharmacogenetic variants. Patients with poor metabolizer phenotypes may have elevated norclobazam levels and subsequent adverse effects. We present a case of an Asian American male receiving clobazam at a standard therapeutic dose for seizure disorder who became comatose secondary to significantly elevated norclobazam concentrations. Genetic testing revealed the patient was a poor CYP2C19 metabolizer, accounting for the impaired clearance. Clinicians should be aware of the patient populations at risk for these genetic polymorphisms and adjust initial doses based on package labeling or consider therapeutic drug monitoring to avoid adverse effects.

11.
Antimicrob Agents Chemother ; 67(10): e0082423, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37768312

RESUMEN

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).


Asunto(s)
Fibrosis Quística , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Femenino , Masculino , Estudios Retrospectivos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas , Fibrosis Quística/microbiología , Antibacterianos/efectos adversos , Evaluación de Resultado en la Atención de Salud
12.
Nutr Clin Pract ; 38(6): 1334-1342, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37537901

RESUMEN

BACKGROUND: Concomitant administration of enteral nutrition (EN) and phenytoin decreases phenytoin absorption. Concerns over impaired nutrition, however, may prevent EN from being held surrounding phenytoin administration. This study aimed to evaluate whether EN holding guidelines impacted nutrition goal achievement in patients taking phenytoin. METHODS: Adult patients administered enteral phenytoin for acute or chronic seizures while receiving EN during a neurocritical care admission 6 months before and after EN holding guideline implementation were eligible. Patients without phenytoin concentrations or a clinical registered dietitian assessment were excluded. The primary outcome was the percentage of nutrition daily goals attained before and after implementation. Secondary end points included the incidence of hypoglycemia, differences in measured phenytoin concentrations, and rates of therapeutic (10-20 mcg/ml) and high-therapeutic (15-20 mcg/ml) concentration attainment. Concentrations were adjusted for hypoalbuminemia using the Winter-Tozer equation. RESULTS: Fifty-five patients representing 412 patient days and 1110 phenytoin administrations were included with 29 preimplementation and 26 postimplementation patients. Median percent attainment of daily EN goals was consistent preimplementation and postimplementation (86% vs 83%, P = 0.48). No significant change in rates of days with hypoglycemia was observed. Adjusted phenytoin concentrations were similar before and after implementation (14.1 vs 15.2 mcg/ml, P = 0.45), but the preimplementation cohort had a lower proportion of high-therapeutic concentrations (23% vs 36%, P = 0.018). CONCLUSION: Holding EN for phenytoin did not impact attainment of daily nutrition goals and was not associated with increased rates of hypoglycemia. This is the first study to evaluate the effect of EN holding on nutrition goals in patients receiving phenytoin.


Asunto(s)
Hipoglucemia , Fenitoína , Adulto , Humanos , Fenitoína/uso terapéutico , Objetivos , Nutrición Enteral , Hipoglucemia/prevención & control
14.
Muscle Nerve ; 67(4): 284-290, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36691226

RESUMEN

INTRODUCTION/AIMS: High-risk medication exposure is a modifiable risk factor for myasthenic exacerbation and crisis. We evaluated whether real-time electronic clinical decision support (CDS) was effective in reducing the rate of prescribing potentially high-risk medications to avoid or use with caution in patients with myasthenia gravis. METHODS: An expert panel reviewed the available drug-disease pairings and associated severity levels to activate the alerts for CDS. All unique alerts activated in both inpatient and outpatient contexts were analyzed over a two-year period. Clinical context, alert severity, medication class, and alert action were collected. The primary outcome was alert override rate. Secondary outcomes included the percentage of unique medication exposures avoided and predictors of alert override. RESULTS: During the analysis period, 2817 unique alerts fired, representing 830 distinct patient-medication exposures for 577 unique patients. The overall alert override rate was 85% (80.3% for inpatient alerts and 95.8% for outpatient alerts). Of unique medication-patient exposures, 19% were avoided because of the alert. Assigned alert severity of "contraindicated" were less likely to be overridden (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.32-0.56), as well as alerts activated during evening staffing (OR 0.69, 95% CI 0.55-0.87). DISCUSSION: Implementation of a myasthenia gravis drug-disease interaction alert reduced overall patient exposure to potentially harmful medications by approximately 19%. Future optimization includes enhanced provider and pharmacist education. Further refinement of alert logic criteria to optimize medication risk reduction and reduce alert fatigue is warranted to support clinicians in prescribing and reduce electronic health record time burden.


Asunto(s)
Sistemas de Apoyo a Decisiones Clínicas , Sistemas de Entrada de Órdenes Médicas , Miastenia Gravis , Humanos , Errores de Medicación , Registros Electrónicos de Salud , Miastenia Gravis/tratamiento farmacológico
15.
AIDS Care ; 35(11): 1635-1646, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-35850626

RESUMEN

Chronic complications are a significant concern for people living with HIV/AIDS (PLWHA) infection. HIV-associated neurocognitive disorders (HAND) are prevalent in PLWHA. Yet, the efficacy of medications that penetrate the central nervous system (CNS) at preventing or slowing the progression of HAND remains largely unknown. The objective of this study was to determine whether high CNS penetration effectiveness (CPE) regimens improve neurocognitive test scores in PLWHA on combined antiretroviral therapy (cART). Primary literature evaluating cognitive outcomes based on CPE score of cART regimens in PLWHA was assembled from PubMed/Medline and EMBASE. Both randomized controlled trials and observational studies with at least 12 weeks of follow-up were included. A meta-analysis was conducted to calculate the standardized mean difference. Eight trials including a total of 3,303 patients with 13,103 person-years of follow-up were included in the systematic review. Four trials (n = 366 patients) met our inclusion criteria and were included in the meta-analysis. In the meta-analysis, HIV regimens with a high CPE score did not affect NPZ-4 or GDS scores (standardized mean difference (SMD) 0.10, 95% CI -0.19, 0.38; I2 = 26%). Future studies with larger sample sizes are warranted to prospectively evaluate the relationship between CPE and progression of HAND.


Asunto(s)
Fármacos Anti-VIH , Trastornos del Conocimiento , Disfunción Cognitiva , Infecciones por VIH , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Sistema Nervioso Central , Disfunción Cognitiva/complicaciones , Trastornos del Conocimiento/etiología
16.
J Trauma Acute Care Surg ; 94(2): 320-327, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35999660

RESUMEN

BACKGROUND: Current Brain Injury Guidelines (BIG) characterize patients with intracranial hemorrhage taking antiplatelet or anticoagulant agents as BIG 3 (the most severe category) regardless of trauma severity. This study assessed the risk of in-hospital mortality or need for neurosurgery in patients taking low-dose aspirin who otherwise would be classified as BIG 1. METHODS: This was a retrospective study at an academic level 1 trauma center. Patients were included if they were admitted with traumatic intracerebral hemorrhage and were evaluated by the BIG criteria. Exclusion criteria included indeterminate BIG status or patients with missing primary outcomes documentation. Patients were categorized as BIG 1, BIG 2, BIG 3, or BIG 1 on aspirin (patients with BIG 1 features taking low-dose aspirin). The primary endpoint was a composite of neurosurgical intervention and all-cause in-hospital mortality. Key secondary endpoints include rate of intracranial hemorrhage progression, and intensive care unit- and hospital-free days. RESULTS: A total of 1,520 patients met the inclusion criteria. Median initial Glasgow Coma Scale was 14 (interquartile range [IQR], 12-15), Injury Severity Scale score was 17 (IQR, 10-25), and Abbreviated Injury Scale subscore head and neck (AIS Head ) was 3 (IQR, 3-4). The rate of the primary outcome for BIG 1, BIG 1 on aspirin, BIG 2, and BIG 3 was 1%, 2.2%, 1%, and 27%, respectively; the difference between BIG 1 on aspirin and BIG 3 was significant ( p < 0.001). CONCLUSION: Patients taking low-dose aspirin with otherwise BIG 1-grade injuries experienced mortality and required neurosurgery significantly less often than other patients categorized as BIG 3. Inclusion of low-dose aspirin in the BIG criteria should be reevaluated. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Humanos , Estudios Retrospectivos , Aspirina/uso terapéutico , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Hemorragias Intracraneales , Escala de Coma de Glasgow
17.
Br J Clin Pharmacol ; 89(3): 931-938, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36575901

RESUMEN

We review pharmacological/prescribing principles relating to metformin according to our mnemonic framework: 'BRAINS & AIMS' (Benefits, Risks, Adverse Effects, Interactions, Necessary prophylaxis, Susceptibilities, Administering, Informing, Monitoring and Stopping): Benefits: Metformin's licensed uses: Type 2 diabetes mellitus (T2DM) treatment, reduction in risk or delay of onset. No clear evidence metformin influences patient-important outcomes [Cochrane Review (2020) of 18 RCTs (n = 10 680)]. Risks: Inexpensive, essential WHO list drug; use contraindicated/not tolerated in 15%: for example, contraindication: lactic acidosis in renal impairment (eGFR <30 mL/min/1.73 m2 ). Adverse effects: Common gastrointestinal (GI) side effects are dose-related and include abdominal pain, decreased appetite, diarrhoea (usually transient), nausea and vomiting, altered taste; vitamin B12 deficiency. Rare: acute metabolic acidosis (lactic acidosis/diabetic ketoacidosis). Interactions (pharmacokinetic) occur with drugs impairing renal function and hence metformin excretion, and drugs inhibiting organic cation transporter 1 or 2 (OCT1, OCT2), and/or multidrug and toxin extrusion protein 1 (MATE1/2-K), such as cimetidine, ranolazine, trimethoprim and verapamil, and inducers such as rifampicin. The risk of hypoglycaemia may increase when metformin is used in combination with other medications for diabetes (pharmacodynamic interaction). Necessary prophylaxis: Detect/treat vitamin B12 deficiency. Susceptible groups: Elderly/renal/liver impairment (lactic acidosis); safe in pregnancy/breastfeeding. Administering: Initially 500 mg once daily (morning) with breakfast; titrate only after 1 week. Informing (relevant BRAINS & A(I)MS principles). Monitoring: Renal function beforehand, and 6-12 monthly, HbA1c 3-6 monthly until controlled. Serum vitamin B12 levels if deficiency is suspected/risk factors for. Stopping: Encourage patients to continue medication, unless deteriorating renal/liver function. Reasons for deprescribing: no harms from stopping suddenly.


Asunto(s)
Acidosis Láctica , Diabetes Mellitus Tipo 2 , Metformina , Insuficiencia Renal , Anciano , Humanos , Acidosis Láctica/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Metformina/uso terapéutico , Proteínas de Transporte de Catión Orgánico/metabolismo , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/complicaciones , Deficiencia de Vitamina B 12/inducido químicamente
18.
Eur Geriatr Med ; 13(6): 1343-1355, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36385690

RESUMEN

PURPOSE: Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents. METHODS: We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events. RESULTS: Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common. CONCLUSIONS: Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required. TRIAL REGISTRATION: ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.


Asunto(s)
Beta vulgaris , COVID-19 , Humanos , Anciano de 80 o más Años , COVID-19/epidemiología , Nitratos/uso terapéutico , Pandemias , Estudios de Factibilidad , Vacunas contra la COVID-19 , Suplementos Dietéticos , Óxidos de Nitrógeno
19.
World J Surg ; 46(11): 2625-2631, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35854014

RESUMEN

BACKGROUND: Bedside percutaneous dilatational tracheostomy (PDT) and percutaneous endoscopic gastrostomy (PEG) are common procedures performed in the intensive care unit (ICU). Venous thromboembolism (VTE) prophylaxis is frequently prescribed to ICU patients and it remains unclear whether pre-procedure discontinuation is necessary. METHODS: This multi-center prospective observational study aimed to describe bleeding rates in patients undergoing bedside PEG or PDT who did or did not have VTE prophylaxis held. Decision to hold prophylaxis was made by the operating physician. The primary endpoint was the rate of peri-procedural bleeding complications. Secondary endpoints included quantification of held doses in the peri-procedural period, rate of venous thromboembolism, and characteristics associated with having prophylaxis held. RESULTS: 91 patients were included over a 2-year period. Patients were on average aged 54 years, 40% female, mostly admitted to the trauma service (59%), and most commonly underwent bedside PDT (59%). Overall, 21% of patients had doses of pre-procedure prophylaxis held. Bleeding events occurred in 1 patient (1.4%) who had prophylaxis continued and in 1 patient (5.0%) who had prophylaxis held, a rate difference of 3.6% (95% CI-9.5%, 16.7%). One bleeding event was managed with bedside surgical repair and one with blood transfusion. There were 10 VTE events, all of whom had prophylaxis continued during the pre-procedure period but 3 had prophylaxis held after the procedure. CONCLUSIONS: Bleeding complications were rare and did not significantly differ depending on whether prophylaxis was held or not. Future research is required to confirm the lack of risk with continuing prophylaxis through bedside procedures.


Asunto(s)
Tromboembolia Venosa , Anticoagulantes/efectos adversos , Femenino , Humanos , Masculino , Estudios Prospectivos , Traqueostomía/métodos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
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