RESUMEN
Orthostatic hypotension is a prevalent clinical condition, caused by heterogenous aetiologies and associated with significant morbidity and mortality. Management is particularly challenging in patients with uncontrolled hypertension. A thorough assessment is needed to draw an appropriate management plan. The treatment aims to improve postural symptoms while minimising side effects and reducing iatrogenic exacerbation of supine hypertension. A personalised management plan including rationalising medications, patient education, identification, and avoidance of triggers, as well as non-pharmacological therapies such as compression devices, dietary modifications, and postural aids, make the first steps. Among pharmacological therapies, midodrine and fludrocortisone are the most prescribed and best studied; pyridostigmine, atomoxetine, and droxidopa are considered next. Yohimbine remains an investigational agent. A multi-disciplinary team may be required in some patients with multiple comorbidities and polypharmacy. However, there's a lack of robust efficacy and safety evidence for all therapies. Building robust real-world and stratified clinical trials based on underlying pathophysiology may pave the way for further drug development and better clinical strategies and in this challenging unmet medical need.
RESUMEN
Medication safety continues to be a problem inside and outside the hospital, partly because new smart technologies can cause new drug-related challenges to prescribers and patients. Better integrated digital and information technology (IT) systems, improved education on prescribing for prescribers and greater patient-centred care that empowers patients to take control of their medications are all vital to safer and more effective prescribing. In July 2021, a roundtable discussion was held as a spin-off meeting of the International Forum on Quality and Safety in Health Care Europe 2021 to discuss challenges and future direction in smart medication management. This manuscript summarises the discussion focusing on the aspects of digital and IT systems, safe prescribing, improved communication and education, and drug adherence.
Asunto(s)
Cumplimiento de la Medicación , Administración del Tratamiento Farmacológico , Comunicación , Europa (Continente) , Humanos , Atención Dirigida al PacienteAsunto(s)
Prescripción Inadecuada/prevención & control , Uso Excesivo de los Servicios de Salud/prevención & control , Pautas de la Práctica en Medicina , Medicina Estatal , Humanos , Prescripción Inadecuada/economía , Prescripción Inadecuada/legislación & jurisprudencia , Prescripción Inadecuada/estadística & datos numéricos , Uso Excesivo de los Servicios de Salud/economía , Uso Excesivo de los Servicios de Salud/legislación & jurisprudencia , Uso Excesivo de los Servicios de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina/economía , Pautas de la Práctica en Medicina/legislación & jurisprudencia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Medicina Estatal/economía , Medicina Estatal/legislación & jurisprudencia , Medicina Estatal/estadística & datos numéricos , Reino UnidoRESUMEN
BACKGROUND: Truly patient-centred care needs to be aligned with what patients consider important, and is highly desirable in the first 24 h of an acute admission, as many decisions are made during this period. However, there is limited knowledge on what matters most to patients in this phase of their hospital stay. The objective of this study was to identify what mattered most to patients in acute care and to assess the patient perspective as to whether their treating doctors were aware of this. METHODS: This was a large-scale, qualitative, flash mob study, conducted simultaneously in sixty-six hospitals in seven countries, starting November 14th 2018, ending 50 h later. One thousand eight hundred fifty adults in the first 24 h of an acute medical admission were interviewed on what mattered most to them, why this mattered and whether they felt the treating doctor was aware of this. RESULTS: The most reported answers to "what matters most (and why)?" were 'getting better or being in good health' (why: to be with family/friends or pick-up life again), 'getting home' (why: more comfortable at home or to take care of someone) and 'having a diagnosis' (why: to feel less anxious or insecure). Of all patients, 51.9% felt the treating doctor did not know what mattered most to them. CONCLUSIONS: The priorities for acutely admitted patients were ostensibly disease- and care-oriented and thus in line with the hospitals' own priorities. However, answers to why these were important were diverse, more personal, and often related to psychological well-being and relations. A large group of patients felt their treating doctor did not know what mattered most to them. Explicitly asking patients what is important and why, could help healthcare professionals to get to know the person behind the patient, which is essential in delivering patient-centred care. TRIAL REGISTRATION: NTR (Netherlands Trial Register) NTR7538 .
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Hospitalización , Proyectos de Investigación , Adulto , Humanos , Tiempo de Internación , Países Bajos , Investigación CualitativaRESUMEN
[Figure: see text].
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Inhibidores de la Angiogénesis/efectos adversos , Endotelio Vascular/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipertensión/inducido químicamente , Indazoles/efectos adversos , Pirimidinas/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Sulfonamidas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Gasto Cardíaco/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hipertensión/fisiopatología , Indazoles/administración & dosificación , Indazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Resistencia Vascular/efectos de los fármacos , Rigidez Vascular/efectos de los fármacosRESUMEN
Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response. Inhibiting CXCR4 in an experimental cancer medicine study by 1-wk continuous infusion of the small-molecule inhibitor AMD3100 (plerixafor) induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immune-mediated damage to noninfected tissues: Rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human pancreatic ductal adenocarcinoma and colorectal cancer by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells.
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Neoplasias Colorrectales/metabolismo , Inmunidad/inmunología , Páncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptores CXCR4/efectos de los fármacos , Receptores CXCR4/metabolismo , Anciano , Bencilaminas , Carcinoma Ductal Pancreático , Quimiocina CXCL12 , Neoplasias Colorrectales/patología , Ciclamas , Femenino , Compuestos Heterocíclicos/antagonistas & inhibidores , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Receptores CCR2/metabolismo , Receptores CXCR3/metabolismo , Receptores CXCR5/metabolismo , Receptores CXCR6/metabolismo , Receptores de Interleucina-8A/metabolismo , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/inmunología , Neoplasias PancreáticasRESUMEN
Hypertension guidelines advise limiting the dose of thiazide diuretics and avoiding combination with ß-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. Two double-blind, placebo-controlled, crossover studies were performed. In study 1 (41 patients), we found that changes in glucose during a 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with bendroflumethiazide. In study 2, 37 patients with essential hypertension received, in random order, 4 weeks of once-daily treatment with hydrochlorothiazide (HCTZ) 25 to 50 mg, nebivolol 5 to 10 mg, combination (HCTZ 25-50 mg+nebivolol 5-10 mg), amiloride (10-20 mg), and placebo. Each drug was force titrated at 2 weeks and separated by a 4-week placebo washout. At each visit, we recorded blood pressure and performed a 75-g oral glucose tolerance test. Primary outcome was the difference in glucose (over the 2 hours of the oral glucose tolerance test) between 0 and 4 weeks, when HCTZ and amiloride were compared by repeated-measures analysis. For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (P<0.0001). Nebivolol did not impair glucose tolerance, either alone or in combination. There was a negative correlation between Δpotassium and Δ2-hour glucose (r=-0.28; P<0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K(+)-sparing diuretic or ß(1)-selective blockade. Substitution or addition of amiloride may be the solution to preventing thiazide-induced diabetes mellitus.
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Amilorida/administración & dosificación , Atenolol/administración & dosificación , Glucemia/efectos de los fármacos , Hidroclorotiazida/administración & dosificación , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Amilorida/efectos adversos , Atenolol/efectos adversos , Determinación de la Presión Sanguínea , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Humanos , Hidroclorotiazida/efectos adversos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Reino UnidoRESUMEN
Elevated plasma homocysteine levels have been associated with higher risks of cardiovascular disease, but the effects on disease rates of supplementation with folic acid to lower plasma homocysteine levels are uncertain. Individual participant data were obtained for a meta-analysis of 8 large, randomized, placebo-controlled trials of folic acid supplementation involving 37 485 individuals at increased risk of cardiovascular disease. The analyses involved intention-to-treat comparisons of first events during the scheduled treatment period. There were 9326 major vascular events (3990 major coronary events, 1528 strokes, and 5068 revascularizations), 3010 cancers, and 5125 deaths. Folic acid allocation yielded an average 25% reduction in homocysteine levels. During a median follow-up of 5 years, folic acid allocation had no significant effects on vascular outcomes, with rate ratios (95% confidence intervals) of 1.01 (0.97-1.05) for major vascular events, 1.03 (0.97-1.10) for major coronary events, and 0.96 (0.87-1.06) for stroke. Likewise, there were no significant effects on vascular outcomes in any of the subgroups studied or on overall vascular mortality. There was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years of it. Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.
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Enfermedades Cardiovasculares/mortalidad , Ácido Fólico/uso terapéutico , Homocisteína/sangre , Homocisteína/efectos de los fármacos , Neoplasias/mortalidad , Complejo Vitamínico B/uso terapéutico , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/tratamiento farmacológico , Causas de Muerte , Intervalos de Confianza , Suplementos Dietéticos , Humanos , Incidencia , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/mortalidad , Insuficiencia del TratamientoAsunto(s)
Defectos de la Visión Cromática/diagnóstico , Servicios de Información , Internet , Médicos/psicología , Estudiantes de Medicina/psicología , Actitud del Personal de Salud , Competencia Clínica , Pruebas de Percepción de Colores , Humanos , Medicina , Optometría , Inhabilitación Médica , Facultades de MedicinaRESUMEN
BACKGROUND: Recent evidence suggests that central aortic blood pressure may be a better predictor of cardiovascular risk than peripheral blood pressure. The central SBP (cSBP) can be estimated from the late systolic shoulder of the radial pulse waveform. We compared the second systolic peak of the radial waveform (pSBP(2)) with the central systolic pressure derived by a generalized transfer function in a large cohort, across a wide age range, of patients from the Anglo-Cardiff Collaborative Trial. We also compared pSBP(2) with the true cSBP measured by cardiac catheterization [invasively measured cSBP (cSBPi)]. METHODS: Noninvasive measurements were made by applanation tonometry using the SphygmoCor device. The aortic pressure waveform was derived from the radial waveform using a validated transfer function. Invasive measures of cSBPi were carried out in a group of 38 patients undergoing diagnostic cardiac angiography, and radial artery pressure waveforms were simultaneously recorded using the SphygmoCor device. RESULTS: Overall, there was a strong correlation (r = 0.99, P<0.001) and good agreement between pSBP(2) and the derived cSBP (mean difference +/- SD 1 +/- 4 mmHg). However, there was a systematic bias with a greater difference between these measures at lower average pressures. There was also a strong correlation and good agreement between the invasively measured cSBPi and pSBP(2) (r = 0.92, P<0.001, mean difference 2 +/- 6 mmHg). CONCLUSION: The second systolic shoulder of the peripheral pressure waveform approximates the cSBP in a large cohort of patients across a wide age range, but this may be inaccurate at low SBP values.